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38 results on '"Stram D.O."'

1. Breast cancer risk factors and survival by tumor subtype: Pooled analyses from the breast cancer association consortium.

Author

Morra A., Jung A.Y., Behrens S., Keeman R., Ahearn T.U., Anton-Culver H., Arndt V., Augustinsson A., Auvinen P.K., Beane Freeman L.E., Becher H., Beckmann M.W., Blomqvist C., Bojesen S.E., Bolla M.K., Brenner H., Briceno I., Brucker S.Y., Camp N.J., Campa D., Canzian F., Castelao J.E., Chanock S.J., Choi J.-Y., Clarke C.L., Couch F.J., Cox A., Cross S.S., Czene K., Dork T., Dunning A.M., Dwek M., Easton D.F., Eccles D.M., Egan K.M., Evans D.G., Fasching P.A., Flyger H., Gago-Dominguez M., Gapstur S.M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Grip M., Guenel P., Haiman C.A., Hakansson N., Hall P., Hamann U., Han S.N., Hart S.N., Hartman M., Heyworth J.S., Hoppe R., Hopper J.L., Hunter D.J., Ito H., Jager A., Jakimovska M., Jakubowska A., Janni W., Kaaks R., Kang D., Kapoor P.M., Kitahara C.M., Koutros S., Kraft P., Kristensen V.N., Lacey J.V., Lambrechts D., Le Marchand L., Li J., Lindblom A., Lubi-Nski J., Lush M., Mannermaa A., Manoochehri M., Margolin S., Mariapun S., Matsuo K., Mavroudis D., Milne R.L., Muranen T.A., Newman W.G., Noh D.-Y., Nordestgaard B.G., Obi N., Olshan A.F., Olsson H., Park-Simon T.-W., Petridis C., Pharoah P.D.P., Plaseska-Karanfilska D., Presneau N., Rashid M.U., Rennert G., Rennert H.S., Rhenius V., Romero A., Saloustros E., Sawyer E.J., Schneeweiss A., Schwentner L., Scott C., Shah M., Shen C.-Y., Shu X.-O., Southey M.C., Stram D.O., Tamimi R.M., Tapper W., Tollenaar R.A.E.M., Tomlinson I., Torres D., Troester M.A., Therese Truong, Vachon C.M., Wang Q., Wang S.S., Williams J.A., Winqvist R., Wolk A., Wu A.H., Yoo K.-Y., Yu J.-C., Zheng W., Ziogas A., Yang X.R., Eliassen A.H., Holmes M.D., Garcia-Closas M., Teo S.H., Schmidt M.K., Chang-Claude J., Morra A., Jung A.Y., Behrens S., Keeman R., Ahearn T.U., Anton-Culver H., Arndt V., Augustinsson A., Auvinen P.K., Beane Freeman L.E., Becher H., Beckmann M.W., Blomqvist C., Bojesen S.E., Bolla M.K., Brenner H., Briceno I., Brucker S.Y., Camp N.J., Campa D., Canzian F., Castelao J.E., Chanock S.J., Choi J.-Y., Clarke C.L., Couch F.J., Cox A., Cross S.S., Czene K., Dork T., Dunning A.M., Dwek M., Easton D.F., Eccles D.M., Egan K.M., Evans D.G., Fasching P.A., Flyger H., Gago-Dominguez M., Gapstur S.M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Grip M., Guenel P., Haiman C.A., Hakansson N., Hall P., Hamann U., Han S.N., Hart S.N., Hartman M., Heyworth J.S., Hoppe R., Hopper J.L., Hunter D.J., Ito H., Jager A., Jakimovska M., Jakubowska A., Janni W., Kaaks R., Kang D., Kapoor P.M., Kitahara C.M., Koutros S., Kraft P., Kristensen V.N., Lacey J.V., Lambrechts D., Le Marchand L., Li J., Lindblom A., Lubi-Nski J., Lush M., Mannermaa A., Manoochehri M., Margolin S., Mariapun S., Matsuo K., Mavroudis D., Milne R.L., Muranen T.A., Newman W.G., Noh D.-Y., Nordestgaard B.G., Obi N., Olshan A.F., Olsson H., Park-Simon T.-W., Petridis C., Pharoah P.D.P., Plaseska-Karanfilska D., Presneau N., Rashid M.U., Rennert G., Rennert H.S., Rhenius V., Romero A., Saloustros E., Sawyer E.J., Schneeweiss A., Schwentner L., Scott C., Shah M., Shen C.-Y., Shu X.-O., Southey M.C., Stram D.O., Tamimi R.M., Tapper W., Tollenaar R.A.E.M., Tomlinson I., Torres D., Troester M.A., Therese Truong, Vachon C.M., Wang Q., Wang S.S., Williams J.A., Winqvist R., Wolk A., Wu A.H., Yoo K.-Y., Yu J.-C., Zheng W., Ziogas A., Yang X.R., Eliassen A.H., Holmes M.D., Garcia-Closas M., Teo S.H., Schmidt M.K., and Chang-Claude J.

Abstract

Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Method(s): We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer. specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Result(s): There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj > 0.30). The strongest associations were between all-cause mortality and BMI >=30 versus 18.5.25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age >=30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0.<5 years versus >=10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen.progestin therapy [0.61 (0.54.0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking. Conclusion(s): We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.Copyright © 2021 American Association for Cancer Research.

Published
2021

2. Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation (vol 5, 4999, 2014)

Author

Ghoussaini, M., Edwards, S.L., Michailidou, K., Nord, S., Lari, R.C.S., Desai, K., Kar, S., Hillman, K.M., Kaufmann, S., Glubb, D.M., Beesley, J., Dennis, J., Bolla, M.K., Wang, Q., Dicks, E., Guo, Q., Schmidt, M.K., Shah, M., Luben, R., Brown, J., Czene, K., Darabi, H., Eriksson, M., Klevebring, D., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Lambrechts, D., Thienpont, B., Neven, P., Wildiers, H., Broeks, A., Van't Veer, L.J., Rutgers, E.J.T., Couch, F.J., Olson, J.E., Hallberg, E., Vachon, C., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Peto, J., dos-Santos-Silva, I., Gibson, L., Nevanlinna, H., Muranen, T.A., Aittomaki, K., Blomqvist, C., Hall, P., Li, J.M., Liu, J.J., Humphreys, K., Kang, D., Choi, J.Y., Park, S.K., Noh, D.Y., Matsuo, K., Ito, H., Iwata, H., Yatabe, Y., Guenel, P., Truong, T., Menegaux, F., Sanchez, M., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Wu, A.H., Tseng, C.C., Berg, D. van den, Stram, D.O., Benitez, J., Zamora, M., Perez, J.I.A., Menendez, P., Shu, X.O., Lu, W., Gao, Y.T., Cai, Q.Y., Cox, A., Cross, S.S., Reed, M.W.R., Andrulis, I.L., Knight, J.A., Glendon, G., Tchatchou, S., Sawyer, E.J., Tomlinson, I., Kerin, M.J., Miller, N., Haiman, C.A., Henderson, B.E., Schumacher, F., Marchand, L. le, Lindblom, A., Margolin, S., Teo, S.H., Yip, C.H., Lee, D.S.C., Wong, T.Y., Hooning, M.J., Martens, J.W.M., Collee, J.M., Deurzen, C.H.M. van, Hopper, J.L., Southey, M.C., Tsimiklis, H., Kapuscinski, M.K., Shen, C.Y., Wu, P.E., Yu, J.C., Chen, S.T., Alnaes, G.G., Borresen-Dale, A.L., Giles, G.G., Milne, R.L., McLean, C., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Hartman, M., Miao, H., Buhari, S.A.B.S., Teo, Y.Y., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Swerdlow, A., Ashworth, A., Orr, N., Schoemaker, M.J., Garcia-Closas, M., Figueroa, J., Chanock, S.J., Lissowska, J., Simard, J., Goldberg, M.S., Labreche, F., Dumont, M., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Brauch, H., Bruning, T., Koto, Y.D., Radice, P., Peterlongo, P., Bonanni, B., Volorio, S., Dork, T., Bogdanova, N.V., Helbig, S., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., Asperen, C.J. van, Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Slager, S., Toland, A.E., Ambrosone, C.B., Yannoukakos, D., Sangrajrang, S., Gaborieau, V., Brennan, P., Mckay, J., Hamann, U., Torres, D., Zheng, W., Long, J.R., Anton-Culver, H., Neuhausen, S.L., Luccarini, C., Baynes, C., Ahmed, S., Maranian, M., Healey, C.S., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Alvarez, N., Herrero, D., Tessier, D.C., Vincent, D., Bacot, F., Santiago, I. de, Carroll, J., Caldas, C., Brown, M.A., Lupien, M., Kristensen, V.N., Pharoah, P.D.P., Chenevix-Trench, G., French, J.D., Easton, D.F., Dunning, A.M., and Australian Ovarian Canc Management

Published
2018

3. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

Author

Lin, W.Y., Camp, N.J., Ghoussaini, M., Beesley, J., Michailidou, K., Hopper, J.L., Apicella, C., Southey, M.C., Stone, J., Schmidt, M.K., Broeks, A., Van't Veer, L.J., Rutgers, E.J.T., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Peto, J., Dos-Santos-Silva, I., Fletcher, O., Johnson, N., Bolla, M.K., Wang, Q., Dennis, J., Sawyer, E.J., Cheng, T., Tomlinson, I., Kerin, M.J., Miller, N., Marme, F., Surowy, H.M., Burwinkel, B., Guenel, P., Truong, T., Menegaux, F., Mulot, C., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Benitez, J., Zamora, M.P., Perez, J.I.A., Menendez, P., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Alvarez, N., Herrera, D., Anton-Culver, H., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Meindl, A., Lichtner, P., Schmutzler, R.K., Muller-Myhsok, B., Brauch, H., Bruning, T., Ko, Y.D., Tessier, D.C., Vincent, D., Bacot, F., Nevanlinna, H., Aittomaki, K., Blomqvist, C., Khan, S., Matsuo, K., Ito, H., Iwata, H., Horio, A., Bogdanova, N.V., Antonenkova, N.N., Dork, T., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Wu, A.H., Tseng, C.C., Berg, D. van den, Stram, D.O., Neven, P., Wauters, E., Wildiers, H., Lambrechts, D., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Radice, P., Peterlongo, P., Manoukian, S., Bonanni, B., Couch, F.J., Wang, X.S., Vachon, C., Purrington, K., Giles, G.G., Milne, R.L., Mclean, C., Haiman, C.A., Henderson, B.E., Schumacher, F., Marchand, L. le, Simard, J., Goldberg, M.S., Labreche, F., Dumont, M., Teo, S.H., Yip, C.H., Hassan, N., Vithana, E.N., Kristensen, V., Zheng, W., Deming-Halverson, S., Shrubsole, M.J., Long, J.R., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Kauppila, S., Andrulis, I.L., Knight, J.A., Glendon, G., Tchatchou, S., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., Asperen, C.J. van, Garcia-Closas, M., Figueroa, J., Lissowska, J., Brinton, L., Czene, K., Darabi, H., Eriksson, M., Brand, J.S., Hooning, M.J., Hollestelle, A., Ouweland, A.M.W. van den, Jager, A., Li, J.M., Liu, J.J., Humphreys, K., Shu, X.O., Lu, W., Gao, Y.T., Cai, H., Cross, S.S., Reed, M.W.R., Blot, W., Signorello, L.B., Cai, Q.Y., Pharoah, P.D.P., Perkins, B., Shah, M., Blows, F.M., Kang, D., Yoo, K.Y., Noh, D.Y., Hartman, M., Miao, H., Chia, K.S., Putti, T.C., Hamann, U., Luccarini, C., Baynes, C., Ahmed, S., Maranian, M., Healey, C.S., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Sangrajrang, S., Gaborieau, V., Brennan, P., Mckay, J., Slager, S., Toland, A.E., Yannoukakos, D., Shen, C.Y., Hsiung, C.N., Wu, P.E., Ding, S.L., Ashworth, A., Jones, M., Orr, N., Swerdlow, A.J., Tsimiklis, H., Makalic, E., Schmidt, D.F., Bui, Q.M., Chanock, S.J., Hunter, D.J., Hein, R., Dahmen, N., Beckmann, L., Aaltonen, K., Muranen, T.A., Heikkinen, T., Irwanto, A., Rahman, N., Turnbull, C.A., Waisfisz, Q., Meijers-Heijboer, H.E.J., Adank, M.A., Luijt, R.B. van der, Hall, P., Chenevix-Trench, G., Dunning, A., Easton, D.F., Cox, A., GENICA Network, kConFab Investigators, Australian Ovarian Canc Study Grp, Breast Ovarian Canc Susceptibility, Clinical Genetics, Obstetrics & Gynecology, Medical Oncology, Cardiothoracic Surgery, Cancer Center Amsterdam, Amsterdam Reproduction & Development (AR&D), Human Genetics, Human genetics, CCA - Oncogenesis, Ghoussaini, Maya [0000-0002-2415-2143], Wang, Jean [0000-0002-9139-0627], Dennis, Joe [0000-0003-4591-1214], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository

Subjects
Genotyping Techniques, Research Support, U.S. Gov't, P.H.S, CASP8 and FADD-Like Apoptosis Regulating Protein, Genome-wide association study, P.H.S, Medical and Health Sciences, Breast and Ovarian Cancer Susceptibility (BOCS) Study, Medizinische Fakultät, Genetics(clinical), Non-U.S. Gov't, Genetics (clinical), Genetics, Genetics & Heredity, variants, Caspase 8, Research Support, Non-U.S. Gov't, Association Studies Articles, General Medicine, Biological Sciences, ddc, Chromosomes, Human, Pair 2, kConFab Investigators, Female, GENICA Network, Australian Ovarian Cancer Study Group, European Continental Ancestry Group, Non-P.H.S, Single-nucleotide polymorphism, Breast Neoplasms, Biology, Research Support, Polymorphism, Single Nucleotide, White People, N.I.H, Breast cancer, Research Support, N.I.H., Extramural, SDG 3 - Good Health and Well-being, medicine, Journal Article, Humans, Genetic Predisposition to Disease, ddc:610, gene, Genotyping, Molecular Biology, Genetic association, disease, Extramural, Proteins, Odds ratio, medicine.disease, susceptibility loci, Minor allele frequency, Case-Control Studies, genome-wide association, enhancers, U.S. Gov't, casp8, Research Support, U.S. Gov't, Non-P.H.S, Genome-Wide Association Study
Abstract

Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regressionmodels adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10-5. Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P=3 × 10-6), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10-9. Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8might be the target gene, suggesting amechanism involving apoptosis.

Published
2016

4. Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2

Author

Orr, N., Dudbridge, F., Dryden, N., Maguire, S., Novo, D., Perrakis, E., Johnson, N., Ghoussaini, M., Hopper, J.L., Southey, M.C., Apicella, C., Stone, J., Schmidt, M.K., Broeks, A., Van't Veer, L.J., Hogervorst, F.B., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Gibson, L., Aitken, Z., Warren, H., Sawyer, E., Tomlinson, I., Kerin, M.J., Miller, N., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Guenel, P., Truong, T., Cordina-Duverger, E., Sanchez, M., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Benitez, J., Zamora, M.P., Perez, J.I.A., Menendez, P., Anton-Culver, H., Neuhausen, S.L., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Hamann, U., Brauch, H., Justenhoven, C., Bruning, T., Ko, Y.D., Nevanlinna, H., Aittomaki, K., Blomqvist, C., Khan, S., Bogdanova, N., Dork, T., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Chenevix-Trench, G., Beesley, J., Lambrechts, D., Moisse, M., Floris, G., Beuselinck, B., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Radice, P., Peterlongo, P., Peissel, B., Pensotti, V., Couch, F.J., Olson, J.E., Slettedahl, S., Vachon, C., Giles, G.G., Milne, R.L., McLean, C., Haiman, C.A., Henderson, B.E., Schumacher, F., Marchand, L. le, Simard, J., Goldberg, M.S., Labreche, F., Dumont, M., Kristensen, V., Alnaes, G.G., Nord, S., Borresen-Dale, A.L., Zheng, W., Deming-Halverson, S., Shrubsole, M., Long, J.R., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Andrulis, I.L., Knight, J.A., Glendon, G., Tchatchou, S., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C.M., Asperen, C.J. van, Garcia-Closas, M., Figueroa, J., Chanock, S.J., Lissowska, J., Czene, K., Darabi, H., Eriksson, M., Klevebring, D., Hooning, M.J., Hollestelle, A., Deurzen, C.H.M. van, Kriege, M., Hall, P., Li, J.M., Liu, J.J., Humphreys, K., Cox, A., Cross, S.S., Reed, M.W.R., Pharoah, P.D.P., Dunning, A.M., Shah, M., Perkins, B.J., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Ashworth, A., Swerdlow, A., Jones, M., Schoemaker, M.J., Meindl, A., Schmutzler, R.K., Olswold, C., Slager, S., Toland, A.E., Yannoukakos, D., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Matsuo, K., Ito, H., Iwata, H., Ishiguro, J., Wu, A.H., Tseng, C.C., Berg, D. van den, Stram, D.O., Teo, S.H., Yip, C.H., Kang, P., Ikram, M.K., Shu, X.O., Lu, W., Gao, Y.T., Cai, H., Kang, D., Choi, J.Y., Park, S.K., Noh, D.Y., Hartman, M., Miao, H., Lim, W.Y., Lee, S.C., Sangrajrang, S., Gaborieau, V., Brennan, P., McKay, J., Wu, P.E., Hou, M.F., Yu, J.C., Shen, C.Y., Blot, W., Cai, Q.Y., Signorello, L.B., Luccarini, C., Bayes, C., Ahmed, S., Maranian, M., Healey, C.S., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Alvarez, N., Herrero, D., Tessier, D.C., Vincent, D., Bacot, F., Hunter, D.J., Lindstrom, S., Dennis, J., Michailidou, K., Bolla, M.K., Easton, D.F., Silva, I.D., Fletcher, O., Peto, J., GENICA Network, kConFab Investigators, Australian Ovarian Canc Study Grp, Obstetrics & Gynecology, Medical Oncology, Pathology, Ophthalmology, Cardiothoracic Surgery, and Clinical Genetics

Subjects
Asian Continental Ancestry Group, Adult, Hepatocyte Nuclear Factor 3-alpha, Risk, binding, European Continental Ancestry Group, Kruppel-Like Transcription Factors, estrogen-receptor-alpha, Breast Neoplasms, GATA3 Transcription Factor, Polymorphism, Single Nucleotide, White People, Kruppel-Like Factor 4, Asian People, SDG 3 - Good Health and Well-being, Medizinische Fakultät, common variants, expression, Humans, Genetic Predisposition to Disease, ddc:610, Genetic Association Studies, Aged, Association Studies Articles, Estrogen Receptor alpha, Chromosome Mapping, foxa1, Middle Aged, confer susceptibility, analyses reveal, Enhancer Elements, Genetic, risk locus, Genetic Loci, functional variants, genome-wide association, Female, Chromosomes, Human, Pair 9
Abstract

We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88-0.92]; P-value = 1.58 × 10(-25)). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08-1.17]; P-value = 7.89 × 10(-09)) and rs13294895 (OR = 1.09 [1.06-1.12]; P-value = 2.97 × 10(-11)). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06-1.18]; P-value = 2.77 × 10(-05)). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis. ispartof: Human Molecular Genetics vol:24 issue:10 pages:2966-84 ispartof: location:England status: published

Published
2015

5. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author

Kar, S.P., Beesley, J., Olama, A. Amin Al, Michailidou, K., Tyrer, J., Kote-Jarai, Z., Lawrenson, K., Lindstrom, S., Ramus, S.J., Thompson, D.J., Kibel, A.S., Dansonka-Mieszkowska, A., Michael, A., Dieffenbach, A.K., Gentry-Maharaj, A., Whittemore, A.S., Wolk, A., Monteiro, A., Peixoto, A., Kierzek, A., Cox, A, Rudolph, A., Gonzalez-Neira, A., Wu, A.H., Lindblom, A., Swerdlow, A., Ziogas, A., Ekici, A.B., Burwinkel, B., Karlan, B.Y., Nordestgaard, B.G., Blomqvist, C., Phelan, C., McLean, C., Pearce, C.L., Vachon, C., Cybulski, C., Slavov, C., Stegmaier, C., Maier, C., Ambrosone, C.B., Hogdall, C.K., Teerlink, C.C., Kang, D., Tessier, D.C., Schaid, D.J., Stram, D.O., Cramer, D.W, Neal, D.E., Eccles, D., Flesch-Janys, D., Edwards, D.R., Wokozorczyk, D., Levine, D.A., Yannoukakos, D., Sawyer, E.J., Bandera, E.V., Poole, E.M., Goode, E.L., Khusnutdinova, E., Hogdall, E., Song, F., Bruinsma, F., Heitz, F., Modugno, F., Hamdy, F.C., Wiklund, F., Giles, G.G., Olsson, H., Wildiers, H., Ulmer, H.U., Pandha, H., Risch, H.A., Darabi, H., Salvesen, H.B., Nevanlinna, H., Gronberg, H., Brenner, H., Brauch, H., Anton-Culver, H., Song, H., Lim, H.Y., McNeish, I., Campbell, I., Vergote, I., Gronwald, J., Lubinski, J., Stanford, J.L., Benitez, J., Doherty, J.A., Permuth, J.B., Chang-Claude, J., Donovan, J.L., Dennis, J., Schildkraut, J.M., Schleutker, J., Hopper, J.L., Kupryjanczyk, J., Park, J.Y., Figueroa, J., Kiemeney, L.A., Massuger, L.F.A.G., et al., Kar, S.P., Beesley, J., Olama, A. Amin Al, Michailidou, K., Tyrer, J., Kote-Jarai, Z., Lawrenson, K., Lindstrom, S., Ramus, S.J., Thompson, D.J., Kibel, A.S., Dansonka-Mieszkowska, A., Michael, A., Dieffenbach, A.K., Gentry-Maharaj, A., Whittemore, A.S., Wolk, A., Monteiro, A., Peixoto, A., Kierzek, A., Cox, A, Rudolph, A., Gonzalez-Neira, A., Wu, A.H., Lindblom, A., Swerdlow, A., Ziogas, A., Ekici, A.B., Burwinkel, B., Karlan, B.Y., Nordestgaard, B.G., Blomqvist, C., Phelan, C., McLean, C., Pearce, C.L., Vachon, C., Cybulski, C., Slavov, C., Stegmaier, C., Maier, C., Ambrosone, C.B., Hogdall, C.K., Teerlink, C.C., Kang, D., Tessier, D.C., Schaid, D.J., Stram, D.O., Cramer, D.W, Neal, D.E., Eccles, D., Flesch-Janys, D., Edwards, D.R., Wokozorczyk, D., Levine, D.A., Yannoukakos, D., Sawyer, E.J., Bandera, E.V., Poole, E.M., Goode, E.L., Khusnutdinova, E., Hogdall, E., Song, F., Bruinsma, F., Heitz, F., Modugno, F., Hamdy, F.C., Wiklund, F., Giles, G.G., Olsson, H., Wildiers, H., Ulmer, H.U., Pandha, H., Risch, H.A., Darabi, H., Salvesen, H.B., Nevanlinna, H., Gronberg, H., Brenner, H., Brauch, H., Anton-Culver, H., Song, H., Lim, H.Y., McNeish, I., Campbell, I., Vergote, I., Gronwald, J., Lubinski, J., Stanford, J.L., Benitez, J., Doherty, J.A., Permuth, J.B., Chang-Claude, J., Donovan, J.L., Dennis, J., Schildkraut, J.M., Schleutker, J., Hopper, J.L., Kupryjanczyk, J., Park, J.Y., Figueroa, J., Kiemeney, L.A., Massuger, L.F.A.G., and et al.

Abstract

Contains fulltext : 172624.pdf (publisher's version ) (Closed access), Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. (c)2016 AACR.This article is highlighted in the In This Issue feature, p. 932.

Published
2016

6. Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium

Author

Milne, R.L., Burwinkel, B., Michailidou, K., Arias-Perez, J.I., Zamora, M.P., Menendez-Rodriguez, P., Hardisson, D., Mendiola, M., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Dennis, J., Wang, Q., Bolla, M.K., Swerdlow, A., Ashworth, A., Orr, N., Schoemaker, M., Ko, Y.D., Brauch, H., Hamann, U., Andrulis, I.L., Knight, J.A., Glendon, G., Tchatchou, S., Matsuo, K., Ito, H., Iwata, H., Tajima, K., Li, J.M., Brand, J.S., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Lambrechts, D., Peuteman, G., Christiaens, M.R., Smeets, A., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Hartman, M., Hui, M., Lim, W.Y., Chan, C.W., Marme, F., Yang, R.X., Bugert, P., Lindblom, A., Margolin, S., Garcia-Closas, M., Chanock, S.J., Lissowska, J., Figueroa, J.D., Bojesen, S.E., Nordestgaard, B.G., Flyger, H., Hooning, M.J., Kriege, M., Ouweland, A.M.W. van den, Koppert, L.B., Fletcher, O., Johnson, N., Dos-Santos-Silva, I., Peto, J., Zheng, W., Deming-Halverson, S., Shrubsole, M.J., Long, J.R., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Cox, A., Cross, S.S., Reed, M.W.R., Schmidt, M.K., Broeks, A., Cornelissen, S., Braaf, L., Kang, D., Choi, J.Y., Park, S.K., Noh, D.Y., Simard, J., Dumont, M., Goldberg, M.S., Labreche, F., Fasching, P.A., Hein, A., Ekici, A.B., Beckmann, M.W., Radice, P., Peterlongo, P., Azzollini, J., Barile, M., Sawyer, E., Tomlinson, I., Kerin, M., Miller, N., Hopper, J.L., Schmidt, D.F., Makalic, E., Southey, M.C., Teo, S.H., Yip, C.H., Sivanandan, K., Tay, W.T., Shen, C.Y., Hsiung, C.N., Yu, J.C., Hou, M.F., Guenel, P., Truong, T., Sanchez, M., Mulot, C., Blot, W., Cai, Q.Y., Nevanlinna, H., Muranen, T.A., Aittomaki, K., Blomqvist, C., Wu, A.H., Tseng, C.C., Berg, D. van den, Stram, D.O., Bogdanova, N., Dork, T., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Shu, X.O., Lu, W., Gao, Y.T., Zhang, B., Couch, F.J., Toland, A.E., Yannoukakos, D., Sangrajrang, S., McKay, J., Wang, X.S., Olson, J.E., Vachon, C., Purrington, K., Severi, G., Baglietto, L., Haiman, C.A., Henderson, B.E., Schumacher, F., Marchand, L. le, Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., Czene, K., Eriksson, M., Humphreys, K., Darabi, H., Ahmed, S., Shah, M., Pharoah, P.D.P., Hall, P., Giles, G.G., Benitez, J., Dunning, A.M., Chenevix-Trench, G., Easton, D.F., GENICA Network, kConFab Investigators, Australian Ovarian Canc Study Grp, TNBCC, Dennis, Joe [0000-0003-4591-1214], Wang, Jean [0000-0002-9139-0627], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository

Subjects
Adult, Ataxin-7, A Kinase Anchor Proteins, Breast Neoplasms, Nerve Tissue Proteins, Middle Aged, Protein Serine-Threonine Kinases, Polymorphism, Single Nucleotide, Cytoskeletal Proteins, Case-Control Studies, Humans, NIMA-Related Kinases, Female, Genetic Predisposition to Disease, health care economics and organizations, Alleles, Genome-Wide Association Study
Abstract

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility\ud variants, although most studies have been underpowered to detect associations of a realistic magnitude.\ud We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which\ud evidence of association with breast cancer risk had been previously reported. Case-control data were combined\ud from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional\ud logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21\ud [rs1053338, per allele OR 5 1.07, 95% confidence interval (CI) 5 1.04–1.10, P 5 2.9 3 1026\ud ], AKAP9-M463I at\ud 7q21 (rs6964587, OR 5 1.05, 95% CI 5 1.03–1.07, P 5 1.7 3 1026\ud ) and NEK10-L513S at 3p24 (rs10510592,\ud OR 5 1.10, 95% CI 5 1.07 –1.12, P 5 5.1 3 10217). The first two associations reached genome-wide statistical\ud significance in a combined analysis of available data, including independent data from nine genome-wide association\ud studies (GWASs): for ATXN7-K264R, OR 5 1.07 (95% CI 5 1.05–1.10, P 5 1.0 3 1028\ud ); for AKAP9-M463I,\ud OR 5 1.05 (95% CI 5 1.04–1.07, P 5 2.0 3 10210). Further analysis of other common variants in these two\ud regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified\ud a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is\ud associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility\ud region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of\ud the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast\ud cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying\ud variants and the genes through which they act.

Published
2014

7. Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium

Author

Johnatty, S.E., Tyrer, J.P., Kar, S., Beesley, J., Lu, Y., Gao, B., Fasching, P.A., Hein, A., Ekici, A.B., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Lambrechts, S., Rossing, M.A., Doherty, J.A., Chang-Claude, J., Modugno, F., Ness, R.B., Moysich, K.B., Levine, D.A., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Gronwald, J., Lubinski, J., Jakubowska, A., Cybulski, C., Brinton, L., Lissowska, J., Wentzensen, N., Song, H., Rhenius, V., Campbell, I., Eccles, D., Sieh, W., Whittemore, A.S., McGuire, V., Rothstein, J.H., Sutphen, R., Anton-Culver, H., Ziogas, A., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Pearce, C.L., Pike, M.C., Stram, D.O., Wu, A.H., Kupryjanczyk, J., Dansonka-Mieszkowska, A., Rzepecka, I.K., Spiewankiewicz, B., Goodman, M.T., Wilkens, L.R., Carney, M.E., Thompson, P.J., Heitz, F., Bois, A. du, Schwaab, I., Harter, P., Pisterer, J., Hillemanns, P., Karlan, B.Y., Walsh, C., Lester, J., Orsulic, S., Winham, S.J., Earp, M., Larson, M.C., Fogarty, Z.C., Hogdall, E., Jensen, A., Kjaer, S.K., Fridley, B.L., Cunningham, J.M., Vierkant, R.A., Schildkraut, J.M., Iversen, E.S., Terry, K.L., Cramer, D.W, Bandera, E.V., Orlow, I., Pejovic, T., Bean, Y., Hogdall, C., Lundvall, L., McNeish, I., Paul, J., Carty, K., Siddiqui, N., Glasspool, R., Sellers, T., Kennedy, C., Chiew, Y.E., Berchuck, A., MacGregor, S., Pharoah, P.D., Goode, E.L., Defazio, A., et al., Johnatty, S.E., Tyrer, J.P., Kar, S., Beesley, J., Lu, Y., Gao, B., Fasching, P.A., Hein, A., Ekici, A.B., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Lambrechts, S., Rossing, M.A., Doherty, J.A., Chang-Claude, J., Modugno, F., Ness, R.B., Moysich, K.B., Levine, D.A., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Gronwald, J., Lubinski, J., Jakubowska, A., Cybulski, C., Brinton, L., Lissowska, J., Wentzensen, N., Song, H., Rhenius, V., Campbell, I., Eccles, D., Sieh, W., Whittemore, A.S., McGuire, V., Rothstein, J.H., Sutphen, R., Anton-Culver, H., Ziogas, A., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Pearce, C.L., Pike, M.C., Stram, D.O., Wu, A.H., Kupryjanczyk, J., Dansonka-Mieszkowska, A., Rzepecka, I.K., Spiewankiewicz, B., Goodman, M.T., Wilkens, L.R., Carney, M.E., Thompson, P.J., Heitz, F., Bois, A. du, Schwaab, I., Harter, P., Pisterer, J., Hillemanns, P., Karlan, B.Y., Walsh, C., Lester, J., Orsulic, S., Winham, S.J., Earp, M., Larson, M.C., Fogarty, Z.C., Hogdall, E., Jensen, A., Kjaer, S.K., Fridley, B.L., Cunningham, J.M., Vierkant, R.A., Schildkraut, J.M., Iversen, E.S., Terry, K.L., Cramer, D.W, Bandera, E.V., Orlow, I., Pejovic, T., Bean, Y., Hogdall, C., Lundvall, L., McNeish, I., Paul, J., Carty, K., Siddiqui, N., Glasspool, R., Sellers, T., Kennedy, C., Chiew, Y.E., Berchuck, A., MacGregor, S., Pharoah, P.D., Goode, E.L., Defazio, A., and et al.

Abstract

Contains fulltext : 152262.pdf (publisher's version ) (Closed access), PURPOSE: Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome. EXPERIMENTAL DESIGN: We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent first-line treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with >/=4 cycles of paclitaxel and carboplatin at standard doses. We evaluated the top SNPs in 4,434 EOC patients, including patients from The Cancer Genome Atlas. In addition, we conducted pathway analysis of all intragenic SNPs and tested their association with PFS and OS using gene set enrichment analysis. RESULTS: Five SNPs were significantly associated (P

Published
2015

8. Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1

Author

Glubb, D.M. (Dylan), Maranian, M. (Melanie), Michailidou, K. (Kyriaki), Pooley, K.A. (Karen), Meyer, K.B. (Kerstin), Kar, S. (Siddhartha), Carlebur, A.F.C., O'Reilly, M. (Marian), Betts, J.A. (Joshua), Hillman, K.M. (Kristine), Kaufmann, S. (Susanne), Beesley, J. (Jonathan), Canisius, S. (Sander), Hopper, J.L. (John), Southey, M.C. (Melissa), Tsimiklis, H. (Helen), Apicella, C. (Carmel), Schmidt, M.K. (Marjanka), Broeks, A. (Annegien), Hogervorst, F.B.L. (Frans), Schoot, C.E. (Ellen) van der, Muir, K.R. (K.), Lophatananon, A. (Artitaya), Stewart-Brown, S. (Sarah), Siriwanarangsan, P. (Pornthep), Fasching, P.A. (Peter), Ruebner, M. (Matthias), Ekici, A.B. (Arif), Beckmann, M.W. (Matthias), Peto, J. (Julian), Santos Silva, I. (Isabel) dos, Fletcher, O. (Olivia), Johnson, N. (Nichola), Pharoah, P.D.P. (Paul D.P.), Bolla, M.K. (Manjeet), Wang, Q. (Qing), Dennis, J. (Joe), Sawyer, E.J. (Elinor), Tomlinson, I.P. (Ian), Kerin, M. (Michael), Miller, N. (Nicola), Burwinkel, B. (Barbara), Marme, F. (Federick), Yang, R. (Rongxi), Surowy, H. (Harald), Guénel, P. (Pascal), Truong, T. (Thérèse), Menegaux, F. (Florence), Sanchez, M. (Marie), Bojesen, S.E. (Stig), Nordestgaard, B.G. (Børge), Nielsen, S.F. (Sune), Flyger, H. (Henrik), González-Neira, A. (Anna), Benítez, J. (Javier), Zamora, M.P. (Pilar), Arias Pérez, J.I. (José Ignacio), Anton-Culver, H. (Hoda), Neuhausen, S.L. (Susan), Brenner, H. (Hermann), Dieffenbach, A.K. (Aida Karina), Arndt, V. (Volker), Stegmaier, C. (Christa), Meindl, A. (Alfons), Schmutzler, R.K. (Rita), Brauch, H. (Hiltrud), Ko, Y.-D. (Yon-Dschun), Brüning, T. (Thomas), Nevanlinna, H. (Heli), Muranen, T.A. (Taru), Aittomäki, K. (Kristiina), Blomqvist, C. (Carl), Matsuo, K. (Keitaro), Ito, H. (Hidemi), Iwata, H. (Hisato), Tanaka, H. (Hideo), Dörk, T. (Thilo), Bogdanova, N.V. (Natalia), Helbig, S. (Sonja), Lindblom, A. (Annika), Margolin, S. (Sara), Mannermaa, A. (Arto), Kataja, V. (Vesa), Kosma, V-M. (Veli-Matti), Hartikainen, J.M. (J.), Wu, A.H. (Anna H.), Tseng, C.-C. (Chiu-Chen), Van Den Berg, D. (David), Stram, D.O. (Daniel O.), Lambrechts, D. (Diether), Zhao, H. (Hui), Weltens, C. (Caroline), Limbergen, E. (Erik) van, Chang-Claude, J. (Jenny), Flesch-Janys, D. (Dieter), Rudolph, A. (Anja), Seibold, P. (Petra), Radice, P. (Paolo), Peterlongo, P. (Paolo), Barile, M. (Monica), Capra, F. (Fabio), Couch, F.J. (Fergus), Olson, J.E. (Janet), Hallberg, B. (Boubou), Vachon, C. (Celine), Giles, G.G. (Graham), Milne, R.L. (Roger), McLean, C.A. (Catriona Ann), Haiman, C.A. (Christopher), Henderson, B.E. (Brian), Schumacher, F.R. (Fredrick), Le Marchand, L. (Loic), Simard, J. (Jacques), Goldberg, M.S. (Mark), Labrèche, F. (France), Dumont, M. (Martine), Teo, S.-H. (Soo-Hwang), Yip, C.H. (Cheng Har), See, M.-H. (Mee-Hoong), Cornes, B.K. (Belinda), Cheng, C-Y. (Ching-Yu), Ikram, M.K. (Kamran), Kristensen, V. (Vessela), Zheng, W. (Wei), Halverson, S.L. (Sandra L.), Shrubsole, M. (Martha), Long, J. (Jirong), Winqvist, R. (Robert), Pykäs, K. (Katri), Jukkola-Vuorinen, A. (Arja), Kauppila, S. (Saila), Andrulis, I.L. (Irene), Knight, J.A. (Julia), Glendon, G. (Gord), Tchatchou, S. (Sandrine), Devilee, P. (Peter), Tollenaar, R.A.E.M. (Rob), Seynaeve, C.M. (Caroline), Asperen, C.J. (Christi) van, García-Closas, M. (Montserrat), Figueroa, J.D. (Jonine), Chanock, S.J. (Stephen), Lissowska, J. (Jolanta), Czene, K. (Kamila), Klevebring, D. (Daniel), Darabi, H. (Hatef), Eriksson, M. (Mikael), Hooning, M.J. (Maartje), Hollestelle, A. (Antoinette), Martens, J.W.M. (John W. M.), Collée, J.M. (Margriet), Hall, P. (Per), Li, J. (Jingmei), Humphreys, K. (Keith), Shu, X.-O. (Xiao-Ou), Lu, W. (Wei), Gao, Y.-T. (Yu-Tang), Cai, H. (Hui), Cox, A. (Angela), Cross, S.S. (Simon), Reed, M.W.R. (Malcolm), Blot, W.J. (William), Signorello, L.B. (Lisa B.), Cai, Q. (Qiuyin), Shah, M. (Mitul), Ghoussaini, M. (Maya), Kang, D. (Daehee), Choi, J.-Y. (J.), Park, S.K. (Sue), Noh, D-Y. (Dong-Young), Hartman, M. (Mikael), Miao, X., Lim, W.-Y. (Wei-Yen), Tang, A. (Anthony), Hamann, U. (Ute), Torres, D. (Diana), Jakubowska, A. (Anna), Lubinski, J. (Jan), Jaworska, K. (Katarzyna), Durda, K. (Katarzyna), Sangrajrang, S. (Suleeporn), Gaborieau, V. (Valerie), Brennan, P. (Paul), McKay, J.D. (James), Olswold, C. (Curtis), Slager, S. (Susan), Toland, A.E. (Amanda), Yannoukakos, D. (Drakoulis), Shen, C-Y. (Chen-Yang), Wu, P.-E. (Pei-Ei), Yu, J-C. (Jyh-Cherng), Hou, M.-F. (Ming-Feng), Swerdlow, A.J. (Anthony ), Ashworth, A. (Alan), Orr, N. (Nick), Jones, M. (Michael), Pita, G. (Guillermo), Alonso, M.R. (Rosario), Álvarez, N. (Nuria), Herrero, D. (Daniel), Tessier, D.C. (Daniel C.), Vincent, D. (Daniel), Bacot, F. (Francois), Luccarini, C. (Craig), Baynes, C. (Caroline), Ahmed, S. (Shahana), Healey, S. (Sue), Brown, M. (Melissa), Ponder, B.A.J. (Bruce A.J.), Chenevix-Trench, G. (Georgia), Thompson, D. (Deborah), Edwards, S.L. (Stacey), Easton, D.F. (Douglas), Dunning, A.M. (Alison), French, J.D. (Juliet), Glubb, D.M. (Dylan), Maranian, M. (Melanie), Michailidou, K. (Kyriaki), Pooley, K.A. (Karen), Meyer, K.B. (Kerstin), Kar, S. (Siddhartha), Carlebur, A.F.C., O'Reilly, M. (Marian), Betts, J.A. (Joshua), Hillman, K.M. (Kristine), Kaufmann, S. (Susanne), Beesley, J. (Jonathan), Canisius, S. (Sander), Hopper, J.L. (John), Southey, M.C. (Melissa), Tsimiklis, H. (Helen), Apicella, C. (Carmel), Schmidt, M.K. (Marjanka), Broeks, A. (Annegien), Hogervorst, F.B.L. (Frans), Schoot, C.E. (Ellen) van der, Muir, K.R. (K.), Lophatananon, A. (Artitaya), Stewart-Brown, S. (Sarah), Siriwanarangsan, P. (Pornthep), Fasching, P.A. (Peter), Ruebner, M. (Matthias), Ekici, A.B. (Arif), Beckmann, M.W. (Matthias), Peto, J. (Julian), Santos Silva, I. (Isabel) dos, Fletcher, O. (Olivia), Johnson, N. (Nichola), Pharoah, P.D.P. (Paul D.P.), Bolla, M.K. (Manjeet), Wang, Q. (Qing), Dennis, J. (Joe), Sawyer, E.J. (Elinor), Tomlinson, I.P. (Ian), Kerin, M. (Michael), Miller, N. (Nicola), Burwinkel, B. (Barbara), Marme, F. (Federick), Yang, R. (Rongxi), Surowy, H. (Harald), Guénel, P. (Pascal), Truong, T. (Thérèse), Menegaux, F. (Florence), Sanchez, M. (Marie), Bojesen, S.E. (Stig), Nordestgaard, B.G. (Børge), Nielsen, S.F. (Sune), Flyger, H. (Henrik), González-Neira, A. (Anna), Benítez, J. (Javier), Zamora, M.P. (Pilar), Arias Pérez, J.I. (José Ignacio), Anton-Culver, H. (Hoda), Neuhausen, S.L. (Susan), Brenner, H. (Hermann), Dieffenbach, A.K. (Aida Karina), Arndt, V. (Volker), Stegmaier, C. (Christa), Meindl, A. (Alfons), Schmutzler, R.K. (Rita), Brauch, H. (Hiltrud), Ko, Y.-D. (Yon-Dschun), Brüning, T. (Thomas), Nevanlinna, H. (Heli), Muranen, T.A. (Taru), Aittomäki, K. (Kristiina), Blomqvist, C. (Carl), Matsuo, K. (Keitaro), Ito, H. (Hidemi), Iwata, H. (Hisato), Tanaka, H. (Hideo), Dörk, T. (Thilo), Bogdanova, N.V. (Natalia), Helbig, S. (Sonja), Lindblom, A. (Annika), Margolin, S. (Sara), Mannermaa, A. (Arto), Kataja, V. (Vesa), Kosma, V-M. (Veli-Matti), Hartikainen, J.M. (J.), Wu, A.H. (Anna H.), Tseng, C.-C. (Chiu-Chen), Van Den Berg, D. (David), Stram, D.O. (Daniel O.), Lambrechts, D. (Diether), Zhao, H. (Hui), Weltens, C. (Caroline), Limbergen, E. (Erik) van, Chang-Claude, J. (Jenny), Flesch-Janys, D. (Dieter), Rudolph, A. (Anja), Seibold, P. (Petra), Radice, P. (Paolo), Peterlongo, P. (Paolo), Barile, M. (Monica), Capra, F. (Fabio), Couch, F.J. (Fergus), Olson, J.E. (Janet), Hallberg, B. (Boubou), Vachon, C. (Celine), Giles, G.G. (Graham), Milne, R.L. (Roger), McLean, C.A. (Catriona Ann), Haiman, C.A. (Christopher), Henderson, B.E. (Brian), Schumacher, F.R. (Fredrick), Le Marchand, L. (Loic), Simard, J. (Jacques), Goldberg, M.S. (Mark), Labrèche, F. (France), Dumont, M. (Martine), Teo, S.-H. (Soo-Hwang), Yip, C.H. (Cheng Har), See, M.-H. (Mee-Hoong), Cornes, B.K. (Belinda), Cheng, C-Y. (Ching-Yu), Ikram, M.K. (Kamran), Kristensen, V. (Vessela), Zheng, W. (Wei), Halverson, S.L. (Sandra L.), Shrubsole, M. (Martha), Long, J. (Jirong), Winqvist, R. (Robert), Pykäs, K. (Katri), Jukkola-Vuorinen, A. (Arja), Kauppila, S. (Saila), Andrulis, I.L. (Irene), Knight, J.A. (Julia), Glendon, G. (Gord), Tchatchou, S. (Sandrine), Devilee, P. (Peter), Tollenaar, R.A.E.M. (Rob), Seynaeve, C.M. (Caroline), Asperen, C.J. (Christi) van, García-Closas, M. (Montserrat), Figueroa, J.D. (Jonine), Chanock, S.J. (Stephen), Lissowska, J. (Jolanta), Czene, K. (Kamila), Klevebring, D. (Daniel), Darabi, H. (Hatef), Eriksson, M. (Mikael), Hooning, M.J. (Maartje), Hollestelle, A. (Antoinette), Martens, J.W.M. (John W. M.), Collée, J.M. (Margriet), Hall, P. (Per), Li, J. (Jingmei), Humphreys, K. (Keith), Shu, X.-O. (Xiao-Ou), Lu, W. (Wei), Gao, Y.-T. (Yu-Tang), Cai, H. (Hui), Cox, A. (Angela), Cross, S.S. (Simon), Reed, M.W.R. (Malcolm), Blot, W.J. (William), Signorello, L.B. (Lisa B.), Cai, Q. (Qiuyin), Shah, M. (Mitul), Ghoussaini, M. (Maya), Kang, D. (Daehee), Choi, J.-Y. (J.), Park, S.K. (Sue), Noh, D-Y. (Dong-Young), Hartman, M. (Mikael), Miao, X., Lim, W.-Y. (Wei-Yen), Tang, A. (Anthony), Hamann, U. (Ute), Torres, D. (Diana), Jakubowska, A. (Anna), Lubinski, J. (Jan), Jaworska, K. (Katarzyna), Durda, K. (Katarzyna), Sangrajrang, S. (Suleeporn), Gaborieau, V. (Valerie), Brennan, P. (Paul), McKay, J.D. (James), Olswold, C. (Curtis), Slager, S. (Susan), Toland, A.E. (Amanda), Yannoukakos, D. (Drakoulis), Shen, C-Y. (Chen-Yang), Wu, P.-E. (Pei-Ei), Yu, J-C. (Jyh-Cherng), Hou, M.-F. (Ming-Feng), Swerdlow, A.J. (Anthony ), Ashworth, A. (Alan), Orr, N. (Nick), Jones, M. (Michael), Pita, G. (Guillermo), Alonso, M.R. (Rosario), Álvarez, N. (Nuria), Herrero, D. (Daniel), Tessier, D.C. (Daniel C.), Vincent, D. (Daniel), Bacot, F. (Francois), Luccarini, C. (Craig), Baynes, C. (Caroline), Ahmed, S. (Shahana), Healey, S. (Sue), Brown, M. (Melissa), Ponder, B.A.J. (Bruce A.J.), Chenevix-Trench, G. (Georgia), Thompson, D. (Deborah), Edwards, S.L. (Stacey), Easton, D.F. (Douglas), Dunning, A.M. (Alison), and French, J.D. (Juliet)

Abstract

Genome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer individuals and control individuals from 52 studies in the Breast Cancer Association Consortium. Multiple logistic regression analyses identified three independent risk signals: the strongest associations were with 15 correlated variants (iCHAV1), where the minor allele of the best candidate, rs62355902, associated with significantly increased risks of both estrogen-receptor-positive (ER+: odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.21-1.27, ptrend = 5.7 × 10-44) and estrogen-receptor-negative (ER-: OR = 1.10, 95% CI = 1.05-1.15, ptrend = 3.0 × 10-4) tumors. After adjustment for rs62355902, we found evidence of association of a further 173 variants (iCHAV2) containing three subsets with a range of effects (the strongest was rs113317823 [pcond = 1.61 × 10-5]) and five variants composing iCHAV3 (lead rs11949391; ER+: OR = 0.90, 95% CI = 0.87-0.93, pcond = 1.4 × 10-4). Twenty-six percent of the prioritized candidate variants coincided with four putative regulatory elements that interact with the MAP3K1 promoter through chromatin looping and affect MAP3K1 promoter activity. Functional analysis indicated that the cancer risk alleles of four candidates (rs74345699 and rs62355900 [iCHAV1], rs16886397 [iCHAV2a], and rs17432750 [iCHAV3]) increased MAP3K1 transcriptional activity. Chromatin immunoprecipitation analysis revealed diminished GATA3 binding to the minor (cancer-protective) allele of rs17432750, indicating a mechanism for its action. We propose that the cancer risk alleles act to increase MAP3K1 expression in vivo and might promote breast cancer cell survival.

Published
2015
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9. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

Author

Michailidou, K. (Kyriaki), Beesley, J. (Jonathan), Lindstrom, S. (Stephen), Canisius, S. (Sander), Dennis, J. (Joe), Lush, M. (Michael), Maranian, M. (Melanie), Bolla, M.K. (Manjeet), Wang, Q. (Qing), Shah, M. (Mitul), Perkins, B. (Barbara), Czene, K. (Kamila), Eriksson, M. (Mikael), Darabi, H. (Hatef), Brand, J.S. (Judith S.), Bojesen, S.E. (Stig), Nordestgaard, B.G. (Børge), Flyger, H. (Henrik), Nielsen, S.F. (Sune), Rahman, N. (Nazneen), Turnbull, C. (Clare), Fletcher, O. (Olivia), Peto, J. (Julian), Gibson, L.J. (Lorna), Santos Silva, I. (Isabel) dos, Chang-Claude, J. (Jenny), Flesch-Janys, D. (Dieter), Rudolph, A. (Anja), Eilber, U. (Ursula), Behrens, T.W. (Timothy), Nevanlinna, H. (Heli), Muranen, T.A. (Taru), Aittomäki, K. (Kristiina), Blomqvist, C. (Carl), Khan, S. (Sofia), Aaltonen, K. (Kirsimari), Ahsan, H. (Habibul), Kibriya, M.G. (Muhammad), Whittemore, A.S. (Alice S.), John, E.M. (Esther M.), Malone, K.E. (Kathleen E.), Gammon, M.D. (Marilie), Santella, R.M. (Regina M.), Ursin, G. (Giske), Makalic, E. (Enes), Schmidt, D.F. (Daniel), Casey, G. (Graham), Hunter, D.J. (David J.), Gapstur, S.M. (Susan M.), Gaudet, M.M. (Mia), Diver, W.R. (Ryan), Haiman, C.A. (Christopher A.), Schumacher, F.R. (Fredrick), Henderson, B.E. (Brian), Le Marchand, L. (Loic), Berg, C.D. (Christine), Chanock, S.J. (Stephen), Figueroa, J.D. (Jonine), Hoover, R.N. (Robert N.), Lambrechts, D. (Diether), Neven, P. (Patrick), Wildiers, H. (Hans), Limbergen, E. (Erik) van, Schmidt, M.K. (Marjanka), Broeks, A. (Annegien), Verhoef, S., Cornelissen, S. (Sten), Couch, F.J. (Fergus), Olson, J.E. (Janet), Hallberg, B. (Boubou), Vachon, C. (Celine), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Adank, M.A. (Muriel), Luijt, R.B. (Rob) van der, Li, J. (Jingmei), Liu, J. (Jianjun), Humphreys, M.K. (Manjeet), Kang, D. (Daehee), Choi, J.-Y. (Ji-Yeob), Park, S.K. (Sue K.), Yoo, K.Y., Matsuo, K. (Keitaro), Ito, H. (Hidemi), Iwata, H. (Hiroji), Tajima, K. (Kazuo), Guénel, P. (Pascal), Truong, T. (Thérèse), Mulot, C. (Claire), Sanchez, M. (Marie), Burwinkel, B. (Barbara), Marme, F. (Federick), Surowy, H. (Harald), Sohn, C. (Christof), Wu, A.H. (Anna H), Tseng, C.-C. (Chiu-chen), Van Den Berg, D. (David), Stram, D.O. (Daniel O.), González-Neira, A. (Anna), Benítez, J. (Javier), Zamora, M.P. (Pilar), Perez, J.I.A. (Jose Ignacio Arias), Shu, X.-O. (Xiao-Ou), Lu, W. (Wei), Gao, Y. (Ying), Cai, H. (Hui), Cox, A. (Angela), Cross, S.S. (Simon), Reed, M.W.R. (Malcolm), Andrulis, I.L. (Irene), Knight, J.A. (Julia), Glendon, G. (Gord), Mulligan, A.-M. (Anna-Marie), Sawyer, E.J. (Elinor), Tomlinson, I.P. (Ian), Kerin, M. (Michael), Miller, N. (Nicola), Lindblom, A. (Annika), Margolin, S. (Sara), Teo, S.H. (Soo Hwang), Yip, C.H. (Cheng Har), Taib, N.A.M. (Nur Aishah Mohd), Tan, G.-H. (Gie-Hooi), Hooning, M.J. (Maartje), Hollestelle, A. (Antoinette), Martens, J.W.M. (John), Collée, J.M. (Margriet), Blot, W.J. (William), Signorello, L.B. (Lisa B.), Cai, Q. (Qiuyin), Hopper, J. (John), Southey, M.C. (Melissa), Tsimiklis, H. (Helen), Apicella, C. (Carmel), Shen, C-Y. (Chen-Yang), Hsiung, C.-N. (Chia-Ni), Wu, P.-E. (Pei-Ei), Hou, M.-F. (Ming-Feng), Kristensen, V. (Vessela), Nord, S. (Silje), Alnæs, G.G. (Grethe), Giles, G.G. (Graham G.), Milne, R.L. (Roger), McLean, C.A. (Catriona Ann), Canzian, F. (Federico), Trichopoulos, D. (Dimitrios), Peeters, P.H.M., Lund, E. (Eiliv), Sund, R. (Reijo), Khaw, K.T., Gunter, M.J. (Marc J.), Palli, D. (Domenico), Mortensen, L.M. (Lotte Maxild), Dossus, L. (Laure), Huerta, J.-M. (Jose-Maria), Meindl, A. (Alfons), Schmutzler, R.K. (Rita), Sutter, C. (Christian), Yang, R. (Rongxi), Muir, K. (Kenneth), Lophatananon, A. (Artitaya), Stewart-Brown, S. (Sarah), Siriwanarangsan, P. (Pornthep), Hartman, J.M. (Joost), Miao, X., Chia, K.S. (Kee Seng), Chan, C.W. (Ching Wan), Fasching, P.A. (Peter), Hein, R. (Rebecca), Beckmann, M.W. (Matthias), Haeberle, L. (Lothar), Brenner, H. (Hermann), Dieffenbach, A.K. (Aida Karina), Arndt, V. (Volker), Stegmaier, C. (Christa), Ashworth, A. (Alan), Orr, N. (Nick), Schoemaker, M. (Minouk), Swerdlow, A.J. (Anthony ), Brinton, L.A. (Louise), García-Closas, M. (Montserrat), Zheng, W. (Wei), Halverson, S.L. (Sandra L.), Shrubsole, M. (Martha), Long, J. (Jirong), Goldberg, M.S. (Mark), Labrèche, F. (France), Dumont, M. (Martine), Winqvist, R. (Robert), Pykäs, K. (Katri), Jukkola-Vuorinen, A. (Arja), Grip, M. (Mervi), Brauch, H. (Hiltrud), Hamann, U. (Ute), Brüning, T. (Thomas), Radice, P. (Paolo), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Bernard, L. (Loris), Bogdanova, N.V. (Natalia), Dörk, T. (Thilo), Mannermaa, A. (Arto), Kataja, V. (Vesa), Kosma, V-M. (Veli-Matti), Hartikainen, J.M. (J.), Devilee, P. (Peter), Tollenaar, R.A.E.M. (Rob), Seynaeve, C.M. (Caroline), Asperen, C.J. (Christi) van, Jakubowska, A. (Anna), Lubinski, J. (Jan), Jaworska, K. (Katarzyna), Huzarski, T. (Tomasz), Sangrajrang, S. (Suleeporn), Gaborieau, V. (Valerie), Brennan, P. (Paul), McKay, J.D. (James), Slager, S. (Susan), Toland, A.E. (Amanda), Ambrosone, C.B. (Christine), Yannoukakos, D. (Drakoulis), Kabisch, M. (Maria), Torres, D. (Diana), Neuhausen, S.L. (Susan), Anton-Culver, H. (Hoda), Luccarini, C. (Craig), Baynes, C. (Caroline), Ahmed, S. (Shahana), Healey, S. (Sue), Tessier, D.C. (Daniel C.), Vincent, D. (Daniel), Bacot, F. (Francois), Pita, G. (Guillermo), Alonso, M.R. (Rosario), Álvarez, N. (Nuria), Herrero, D. (Daniel), Simard, J. (Jacques), Pharoah, P.P.D.P. (Paul P.D.P.), Kraft, P. (Peter), Dunning, A.M. (Alison), Chenevix-Trench, G. (Georgia), Hall, P. (Per), Easton, D.F. (Douglas), Michailidou, K. (Kyriaki), Beesley, J. (Jonathan), Lindstrom, S. (Stephen), Canisius, S. (Sander), Dennis, J. (Joe), Lush, M. (Michael), Maranian, M. (Melanie), Bolla, M.K. (Manjeet), Wang, Q. (Qing), Shah, M. (Mitul), Perkins, B. (Barbara), Czene, K. (Kamila), Eriksson, M. (Mikael), Darabi, H. (Hatef), Brand, J.S. (Judith S.), Bojesen, S.E. (Stig), Nordestgaard, B.G. (Børge), Flyger, H. (Henrik), Nielsen, S.F. (Sune), Rahman, N. (Nazneen), Turnbull, C. (Clare), Fletcher, O. (Olivia), Peto, J. (Julian), Gibson, L.J. (Lorna), Santos Silva, I. (Isabel) dos, Chang-Claude, J. (Jenny), Flesch-Janys, D. (Dieter), Rudolph, A. (Anja), Eilber, U. (Ursula), Behrens, T.W. (Timothy), Nevanlinna, H. (Heli), Muranen, T.A. (Taru), Aittomäki, K. (Kristiina), Blomqvist, C. (Carl), Khan, S. (Sofia), Aaltonen, K. (Kirsimari), Ahsan, H. (Habibul), Kibriya, M.G. (Muhammad), Whittemore, A.S. (Alice S.), John, E.M. (Esther M.), Malone, K.E. (Kathleen E.), Gammon, M.D. (Marilie), Santella, R.M. (Regina M.), Ursin, G. (Giske), Makalic, E. (Enes), Schmidt, D.F. (Daniel), Casey, G. (Graham), Hunter, D.J. (David J.), Gapstur, S.M. (Susan M.), Gaudet, M.M. (Mia), Diver, W.R. (Ryan), Haiman, C.A. (Christopher A.), Schumacher, F.R. (Fredrick), Henderson, B.E. (Brian), Le Marchand, L. (Loic), Berg, C.D. (Christine), Chanock, S.J. (Stephen), Figueroa, J.D. (Jonine), Hoover, R.N. (Robert N.), Lambrechts, D. (Diether), Neven, P. (Patrick), Wildiers, H. (Hans), Limbergen, E. (Erik) van, Schmidt, M.K. (Marjanka), Broeks, A. (Annegien), Verhoef, S., Cornelissen, S. (Sten), Couch, F.J. (Fergus), Olson, J.E. (Janet), Hallberg, B. (Boubou), Vachon, C. (Celine), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Adank, M.A. (Muriel), Luijt, R.B. (Rob) van der, Li, J. (Jingmei), Liu, J. (Jianjun), Humphreys, M.K. (Manjeet), Kang, D. (Daehee), Choi, J.-Y. (Ji-Yeob), Park, S.K. (Sue K.), Yoo, K.Y., Matsuo, K. (Keitaro), Ito, H. (Hidemi), Iwata, H. (Hiroji), Tajima, K. (Kazuo), Guénel, P. (Pascal), Truong, T. (Thérèse), Mulot, C. (Claire), Sanchez, M. (Marie), Burwinkel, B. (Barbara), Marme, F. (Federick), Surowy, H. (Harald), Sohn, C. (Christof), Wu, A.H. (Anna H), Tseng, C.-C. (Chiu-chen), Van Den Berg, D. (David), Stram, D.O. (Daniel O.), González-Neira, A. (Anna), Benítez, J. (Javier), Zamora, M.P. (Pilar), Perez, J.I.A. (Jose Ignacio Arias), Shu, X.-O. (Xiao-Ou), Lu, W. (Wei), Gao, Y. (Ying), Cai, H. (Hui), Cox, A. (Angela), Cross, S.S. (Simon), Reed, M.W.R. (Malcolm), Andrulis, I.L. (Irene), Knight, J.A. (Julia), Glendon, G. (Gord), Mulligan, A.-M. (Anna-Marie), Sawyer, E.J. (Elinor), Tomlinson, I.P. (Ian), Kerin, M. (Michael), Miller, N. (Nicola), Lindblom, A. (Annika), Margolin, S. (Sara), Teo, S.H. (Soo Hwang), Yip, C.H. (Cheng Har), Taib, N.A.M. (Nur Aishah Mohd), Tan, G.-H. (Gie-Hooi), Hooning, M.J. (Maartje), Hollestelle, A. (Antoinette), Martens, J.W.M. (John), Collée, J.M. (Margriet), Blot, W.J. (William), Signorello, L.B. (Lisa B.), Cai, Q. (Qiuyin), Hopper, J. (John), Southey, M.C. (Melissa), Tsimiklis, H. (Helen), Apicella, C. (Carmel), Shen, C-Y. (Chen-Yang), Hsiung, C.-N. (Chia-Ni), Wu, P.-E. (Pei-Ei), Hou, M.-F. (Ming-Feng), Kristensen, V. (Vessela), Nord, S. (Silje), Alnæs, G.G. (Grethe), Giles, G.G. (Graham G.), Milne, R.L. (Roger), McLean, C.A. (Catriona Ann), Canzian, F. (Federico), Trichopoulos, D. (Dimitrios), Peeters, P.H.M., Lund, E. (Eiliv), Sund, R. (Reijo), Khaw, K.T., Gunter, M.J. (Marc J.), Palli, D. (Domenico), Mortensen, L.M. (Lotte Maxild), Dossus, L. (Laure), Huerta, J.-M. (Jose-Maria), Meindl, A. (Alfons), Schmutzler, R.K. (Rita), Sutter, C. (Christian), Yang, R. (Rongxi), Muir, K. (Kenneth), Lophatananon, A. (Artitaya), Stewart-Brown, S. (Sarah), Siriwanarangsan, P. (Pornthep), Hartman, J.M. (Joost), Miao, X., Chia, K.S. (Kee Seng), Chan, C.W. (Ching Wan), Fasching, P.A. (Peter), Hein, R. (Rebecca), Beckmann, M.W. (Matthias), Haeberle, L. (Lothar), Brenner, H. (Hermann), Dieffenbach, A.K. (Aida Karina), Arndt, V. (Volker), Stegmaier, C. (Christa), Ashworth, A. (Alan), Orr, N. (Nick), Schoemaker, M. (Minouk), Swerdlow, A.J. (Anthony ), Brinton, L.A. (Louise), García-Closas, M. (Montserrat), Zheng, W. (Wei), Halverson, S.L. (Sandra L.), Shrubsole, M. (Martha), Long, J. (Jirong), Goldberg, M.S. (Mark), Labrèche, F. (France), Dumont, M. (Martine), Winqvist, R. (Robert), Pykäs, K. (Katri), Jukkola-Vuorinen, A. (Arja), Grip, M. (Mervi), Brauch, H. (Hiltrud), Hamann, U. (Ute), Brüning, T. (Thomas), Radice, P. (Paolo), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Bernard, L. (Loris), Bogdanova, N.V. (Natalia), Dörk, T. (Thilo), Mannermaa, A. (Arto), Kataja, V. (Vesa), Kosma, V-M. (Veli-Matti), Hartikainen, J.M. (J.), Devilee, P. (Peter), Tollenaar, R.A.E.M. (Rob), Seynaeve, C.M. (Caroline), Asperen, C.J. (Christi) van, Jakubowska, A. (Anna), Lubinski, J. (Jan), Jaworska, K. (Katarzyna), Huzarski, T. (Tomasz), Sangrajrang, S. (Suleeporn), Gaborieau, V. (Valerie), Brennan, P. (Paul), McKay, J.D. (James), Slager, S. (Susan), Toland, A.E. (Amanda), Ambrosone, C.B. (Christine), Yannoukakos, D. (Drakoulis), Kabisch, M. (Maria), Torres, D. (Diana), Neuhausen, S.L. (Susan), Anton-Culver, H. (Hoda), Luccarini, C. (Craig), Baynes, C. (Caroline), Ahmed, S. (Shahana), Healey, S. (Sue), Tessier, D.C. (Daniel C.), Vincent, D. (Daniel), Bacot, F. (Francois), Pita, G. (Guillermo), Alonso, M.R. (Rosario), Álvarez, N. (Nuria), Herrero, D. (Daniel), Simard, J. (Jacques), Pharoah, P.P.D.P. (Paul P.D.P.), Kraft, P. (Peter), Dunning, A.M. (Alison), Chenevix-Trench, G. (Georgia), Hall, P. (Per), and Easton, D.F. (Douglas)

Abstract

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10 â '8. Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.

Published
2015
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10. Large-scale genotyping identifies 41 new loci associated with breast cancer risk

Author

Michailidou, K., Hall, P., Gonzalez-Neira, A., Ghoussaini, M., Dennis, J., Milne, R.L., Schmidt, M.K., Chang-Claude, J., Bojesen, S.E., Bolla, M.K., Wang, Q., Dicks, E., Lee, A., Turnbull, C., Rahman, N., Fletcher, O., Peto, J., Gibson, L., Silva, I.D., Nevanlinna, H., Muranen, T.A., Aittomaki, K., Blomqvist, C., Czene, K., Irwanto, A., Liu, J.J., Waisfisz, Q., Meijers-Heijboer, H., Adank, M., Luijt, R.B. van der, Hein, R., Dahmen, N., Beckman, L., Meindl, A., Schmutzler, R.K., Muller-Myhsok, B., Lichtner, P., Hopper, J.L., Southey, M.C., Makalic, E., Schmidt, D.F., Uitterlinden, A.G., Hofman, A., Hunter, D.J., Chanock, S.J., Vincent, D., Bacot, F., Tessier, D.C., Canisius, S., Wessels, L.F.A., Haiman, C.A., Shah, M., Luben, R., Brown, J., Luccarini, C., Schoof, N., Humphreys, K., Li, J.M., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Couch, F.J., Wang, X.S., Vachon, C., Stevens, K.N., Lambrechts, D., Moisse, M., Paridaens, R., Christiaens, M.R., Rudolph, A., Nickels, S., Flesch-Janys, D., Johnson, N., Aitken, Z., Aaltonen, K., Heikkinen, T., Broeks, A., Van't Veer, L.J., Schoot, C.E. van der, Guenel, P., Truong, T., Laurent-Puig, P., Menegaux, F., Marme, F., Schneeweiss, A., Sohn, C., Burwinke, B., Zamora, M.P., Perez, J.I.A., Pita, G., Alonso, M.R., Cox, A., Brock, I.W., Cross, S.S., Reed, M.W.R., Sawyer, E.J., Tomlinson, I., Kerin, M.J., Miller, N., Henderson, B.E., Schumacher, F., Marchand, L. le, Andrulis, I.L., Knight, J.A., Glendon, G., Mulligan, A.M., Lindblom, A., Margolin, S., Hooning, M.J., Hollestelle, A., Ouweland, A.M.W. van den, Jager, A., Bui, Q.M., Stone, J., Dite, G.S., Apicella, C., Tsimiklis, H., Giles, G.G., Severi, G., Baglietto, L., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Brenner, H., Muller, H., Arndt, V., Stegmaier, C., Swerdlown, A., Ashworth, A., Orr, N., Jones, M., Figueroa, J., Lissowska, J., Brinton, L., Goldberg, M.S., Labreche, F., Dumont, M., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Brauch, H., Hamann, U., Bruning, T., Radice, P., Peterlongo, P., Manouldan, S., Bonanni, B., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., Asperen, C.J. van, Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Bogdanova, N.V., Antonenkova, N.N., Dork, T., Kristensen, V.N., Anton-Culver, H., Slager, S., Toland, A.E., Edge, S., Fostira, F., Kang, D., Yoo, K.Y., Noh, D.Y., Matsuo, K., Ito, H., Iwata, H., Sueta, A., Wu, A.H., Tseng, C.C., Berg, D. van den, Stram, D.O., Shu, X.O., Lu, W., Gao, Y.T., Cai, H., Teo, S.H., Yip, C.H., Phuah, S.Y., Cornes, B.K., Hartman, M., Miao, H., Lim, W.Y., Sng, J.H., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Shen, C.Y., Hsiung, C.N., Wu, P.E., Ding, S.L., Sangrajrang, S., Gaborieau, V., Brennan, P., Mckay, J., Blot, W.J., Signorello, L.B., Cai, Q.Y., Zheng, W., Deming-Halverson, S., Shrubsole, M., Long, J.R., Simard, J., Garcia-Closas, M., Pharoah, P.D.P., Chenevix-Trench, G., Dunning, A.M., Benitez, J., Easton, D.F., Breast Ovarian Canc Susceptibility, Hereditary Breast Ovarian Canc Res, kConFab Investigators, Australian Ovarian Can Study Grp, GENICA Gene Environm Interaction B, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Human Genetics, Landsteiner Laboratory, Clinical Haematology, Clinical Genetics, Internal Medicine, Epidemiology, Medical Oncology, Cardiothoracic Surgery, Human genetics, CCA - Oncogenesis, and ~

Subjects
signaling pathway, Genotyping, Genotype, Single-nucleotide polymorphism, Genome-wide association study, Breast Neoplasms, consortium, Biology, Case-Control Studies, Cooperative Behavior, Female, Gene-Environment Interaction, Genetic Loci, Genome-Wide Association Study, Humans, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Risk Factors, Genetic Predisposition to Disease, Genetics, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, common variants, expression, medicine, Polymorphism, gene, hormone-related protein, 030304 developmental biology, Genetic association, 0303 health sciences, Breast cancer susceptibility, Cancer, Single Nucleotide, medicine.disease, confer susceptibility, susceptibility loci, 3. Good health, 14q24.1 rad51l1, TOX3, 030220 oncology & carcinogenesis, genome-wide association
Abstract

Journal article Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ~9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10!¿8). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility. European Community Seventh Framework Programme - grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) peer-reviewed

Published
2013

11. A comprehensive analysis of common IGF1, IGFBP1 and IGFBP3 genetic variation with prospective IGF-I and IGFBP-3 blood levels and prostate cancer risk among Caucasians

Author

Schumacher, F.R. Cheng, I. Freedman, M.L. Mucci, L. Allen, N.E. Pollak, M.N. Hayes, R.B. Stram, D.O. Canzian, F. Henderson, B.E. Hunter, D.J. Virtamo, J. Manjer, J. Gaziano, J.M. Kolone, L.N. Tjønneland, A. Albanes, D. Calle, E.E. Giovannucci, E. David Crawford, E. Haiman, C.A. Kraft, P. Willett, W.C. Thun, M.J. Le Marchand, L. Kaaks, R. Feigelson, H.S. Bueno-de-Mesquita, H.B. Palli, D. Riboli, E. Lund, E. Amiano, P. Andriole, G. Dunning, A.M. Trichopoulos, D. Stampfer, M.J. Key, T.J. Ma, J.

Abstract

The insulin-like growth factor (IGF) pathway has been implicated in prostate development and carcinogenesis. We conducted a comprehensive analysis, utilizing a resequencing and tagging single-nucleotide polymorphism (SNP) approach, between common genetic variation in the IGF1, IGF binding protein (BP) 1, and IGFBP3 genes with IGF-I and IGFBP-3 blood levels, and prostate cancer (PCa) risk, among Caucasians in the NCI Breast and Prostate Cancer Cohort Consortium. We genotyped 14 IGF1 SNPs and 16 IGFBP1/ IGFBP3 SNPs to capture common [minor allele frequency (MAF) ≥ 5%] variation among Caucasians. For each SNP, we assessed the geometric mean difference in IGF blood levels (N = 5684) across genotypes and the association with PCa risk (6012 PCa cases/6641 controls). We present two-sided statistical tests and correct for multiple comparisons. A non-synonymous IGFBP3 SNP in exon 1, rs2854746 (Gly32Ala), was associated with IGFBP-3 blood levels (Padj = 8.8 × 10-43) after adjusting for the previously established IGFBP3 promoter polymorphism A-202C (rs2854744); IGFBP-3 blood levels were 6.3% higher for each minor allele. For IGF1 SNP rs4764695, the risk estimates among heterozygotes was 1.01 (99% CI: 0.90-1.14) and 1.20 (99% CI: 1.06-1.37) for variant homozygotes with overall PCa risk. The corrected allelic P-value was 8.7 × 10-3. IGF-I levels were significantly associated with PCa risk (Ptrend = 0.02) with a 21% increase of PCa risk when compared with the highest quartile to the lowest quartile. We have identified SNPs significantly associated with IGFBP-3 blood levels, but none of these alter PCa risk; however, a novel IGF1 SNP, not associated with IGF-I blood levels, shows preliminary evidence for association with PCa risk among Caucasians. © The Author 2010. Published by Oxford University Press. All rights reserved.

Published
2010

12. Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation

Author

Ghoussaini, M. (Maya), Edwards, S.L. (Stacey), Michailidou, K. (Kyriaki), Nord, S. (Silje), Cowper-Sallari, R. (Richard), Desai, K. (Kinjal), Kar, S. (Siddhartha), Hillman, K.M. (Kristine), Kaufmann, S. (Susanne), Glubb, D.M. (Dylan), Beesley, J. (Jonathan), Dennis, J. (Joe), Bolla, M.K. (Manjeet), Wang, Q. (Qing), Dicks, E. (Ed), Guo, Q. (Qi), Schmidt, M.K. (Marjanka), Shah, M. (Mitul), Luben, R.N. (Robert), Brown, J. (Judith), Czene, K. (Kamila), Darabi, H. (Hatef), Eriksson, M. (Mats), Klevebring, D. (Daniel), Bojesen, S.E. (Stig), Nordestgaard, B.G. (Børge), Nielsen, S.F. (Sune), Flyger, H. (Henrik), Lambrechts, D. (Diether), Thienpont, B. (Bernard), Neven, P. (Patrick), Wildiers, H. (Hans), Broeks, A. (Annegien), Veer, L.J. (Laura) van 't, Rutgers, E.J.T. (Emiel), Couch, F.J. (Fergus), Olson, J.E. (Janet), Hallberg, B. (Boubou), Vachon, C. (Celine), Chang-Claude, J. (Jenny), Rudolph, A. (Anja), Seibold, P. (Petra), Flesch-Janys, D. (Dieter), Peto, J. (Julian), Santos Silva, I. (Isabel) dos, Gibson, L.J. (Lorna), Nevanlinna, H. (Heli), Muranen, T.A. (Taru), Aittomäki, K. (Kristiina), Blomqvist, C. (Carl), Hall, P. (Per), Li, J. (Jingmei), Liu, J. (Jianjun), Humphreys, M.K. (Manjeet), Kang, D. (Daehee), Choi, J.-Y. (J.), Park, S.K. (Sue), Noh, D-Y. (Dong-Young), Matsuo, K. (Keitaro), Ito, H. (Hidemi), Iwata, H. (Hisato), Yatabe, Y. (Yasushi), Guénel, P. (Pascal), Truong, T. (Thérèse), Menegaux, F. (Florence), Sanchez, M. (Marie), Burwinkel, B. (Barbara), Marme, F. (Federick), Schneeweiss, A. (Andreas), Sohn, C. (Christof), Wu, A.H. (Anna H.), Tseng, C.-C. (Chiu-Chen), Van Den Berg, D. (David), Stram, D.O. (Daniel O.), Benítez, J. (Javier), Zamora, M.P. (Pilar), Perez, J.I.A. (Jose Ignacio Arias), Menéndez, P. (Primitiva), Shu, X.-O. (Xiao-Ou), Lu, W. (Wei), Gao, Y. (Ying), Cai, Q. (Qiuyin), Cox, A. (Angela), Cross, S.S. (Simon), Reed, M.W.R. (Malcolm), Andrulis, I.L. (Irene), Knight, J.A. (Julia), Glendon, G. (Gord), Tchatchou, S. (Sandrine), Sawyer, E.J. (Elinor), Tomlinson, I.P. (Ian), Kerin, M. (Michael), Miller, N. (Nicola), Haiman, C.A. (Christopher), Henderson, B.E. (Brian), Schumacher, F.R. (Fredrick), Le Marchand, L. (Loic), Lindblom, A. (Annika), Margolin, S. (Sara), Teo, S.-H. (Soo-Hwang), Yip, C.H. (Cheng Har), Lee, D.S.C. (Daphne S.C.), Wong, T.Y. (Tien Yin), Hooning, M.J. (Maartje), Martens, J.W.M. (John W. M.), Collée, J.M. (Margriet), Deurzen, C.H.M. (Carolien) van, Hopper, J.L. (John), Southey, M.C. (Melissa), Tsimiklis, H. (Helen), Kapuscinski, M.K. (Miroslav K.), Shen, C-Y. (Chen-Yang), Wu, P.-E. (Pei-Ei), Yu, J-C. (Jyh-Cherng), Chen, S.-T., Alnæs, G.G. (Grethe), Borresen-Dale, A.-L. (Anne-Lise), Giles, G.G. (Graham), Milne, R.L. (Roger), McLean, C.A. (Catriona Ann), Muir, K.R. (K.), Lophatananon, A. (Artitaya), Stewart-Brown, S. (Sarah), Siriwanarangsan, P. (Pornthep), Hartman, M. (Mikael), Miao, X., Buhari, S.A.B.S. (Shaik Ahmad Bin Syed), Teo, Y.Y. (Yik Ying), Fasching, P.A. (Peter), Haeberle, L. (Lothar), Ekici, A.B. (Arif), Beckmann, M.W. (Matthias), Brenner, H. (Hermann), Dieffenbach, A.K. (Aida Karina), Arndt, V. (Volker), Stegmaier, C. (Christa), Swerdlow, A.J. (Anthony ), Ashworth, A. (Alan), Orr, N. (Nick), Schoemaker, M. (Minouk), García-Closas, M. (Montserrat), Figueroa, J.D. (Jonine), Chanock, S.J. (Stephen), Lissowska, J. (Jolanta), Simard, J. (Jacques), Goldberg, M.S. (Mark), Labrèche, F. (France), Dumont, M. (Martine), Winqvist, R. (Robert), Pykäs, K. (Katri), Jukkola-Vuorinen, A. (Arja), Brauch, H. (Hiltrud), Brüning, T. (Thomas), Koto, Y.-D. (Yon-Dschun), Radice, P. (Paolo), Peterlongo, P. (Paolo), Bonnani, B. (Bernardo), Volorio, S. (Sara), Dörk, T. (Thilo), Bogdanova, N.V. (Natalia), Helbig, S. (Sonja), Mannermaa, A. (Arto), Kataja, V. (Vesa), Kosma, V-M. (Veli-Matti), Hartikainen, J.M. (J.), Devilee, P. (Peter), Tollenaar, R.A.E.M. (Rob), Seynaeve, C.M. (Caroline), Asperen, C.J. (Christi) van, Jakubowska, A. (Anna), Lubinski, J. (Jan), Jaworska-Bieniek, K. (Katarzyna), Durda, K. (Katarzyna), Slager, S. (Susan), Toland, A.E. (Amanda), Ambrosone, C.B. (Christine), Yannoukakos, D. (Drakoulis), Sangrajrang, S. (Suleeporn), Gaborieau, V. (Valerie), Brennan, P. (Paul), McKay, J.D. (James), Hamann, U. (Ute), Torres, D. (Diana), Zheng, W. (Wei), Long, J. (Jirong), Anton-Culver, H. (Hoda), Neuhausen, S.L. (Susan), Luccarini, C. (Craig), Baynes, C. (Caroline), Ahmed, S. (Shahana), Maranian, M. (Melanie), Healey, S. (Sue), González-Neira, A. (Anna), Pita, G. (Guillermo), Alonso, M.R. (Rosario), Álvarez, N. (Nuria), Herrero, D. (Daniel), Tessier, D.C. (Daniel C.), Vincent, D. (Daniel), Bacot, F. (Francois), Santiago, I. (Ines) de, Carroll, J. (Jason), Caldas, C. (Carlos), Brown, M. (Melissa), Lupien, M. (Mathieu), Kristensen, V. (Vessela), Pharoah, P.D.P. (Paul), Chenevix-Trench, G. (Georgia), French, J.D. (Juliet), Easton, D.F. (Douglas), Dunning, A.M. (Alison), Webb, P. (Penny), De Fazio, A. (Anna), Ghoussaini, M. (Maya), Edwards, S.L. (Stacey), Michailidou, K. (Kyriaki), Nord, S. (Silje), Cowper-Sallari, R. (Richard), Desai, K. (Kinjal), Kar, S. (Siddhartha), Hillman, K.M. (Kristine), Kaufmann, S. (Susanne), Glubb, D.M. (Dylan), Beesley, J. (Jonathan), Dennis, J. (Joe), Bolla, M.K. (Manjeet), Wang, Q. (Qing), Dicks, E. (Ed), Guo, Q. (Qi), Schmidt, M.K. (Marjanka), Shah, M. (Mitul), Luben, R.N. (Robert), Brown, J. (Judith), Czene, K. (Kamila), Darabi, H. (Hatef), Eriksson, M. (Mats), Klevebring, D. (Daniel), Bojesen, S.E. (Stig), Nordestgaard, B.G. (Børge), Nielsen, S.F. (Sune), Flyger, H. (Henrik), Lambrechts, D. (Diether), Thienpont, B. (Bernard), Neven, P. (Patrick), Wildiers, H. (Hans), Broeks, A. (Annegien), Veer, L.J. (Laura) van 't, Rutgers, E.J.T. (Emiel), Couch, F.J. (Fergus), Olson, J.E. (Janet), Hallberg, B. (Boubou), Vachon, C. (Celine), Chang-Claude, J. (Jenny), Rudolph, A. (Anja), Seibold, P. (Petra), Flesch-Janys, D. (Dieter), Peto, J. (Julian), Santos Silva, I. (Isabel) dos, Gibson, L.J. (Lorna), Nevanlinna, H. (Heli), Muranen, T.A. (Taru), Aittomäki, K. (Kristiina), Blomqvist, C. (Carl), Hall, P. (Per), Li, J. (Jingmei), Liu, J. (Jianjun), Humphreys, M.K. (Manjeet), Kang, D. (Daehee), Choi, J.-Y. (J.), Park, S.K. (Sue), Noh, D-Y. (Dong-Young), Matsuo, K. (Keitaro), Ito, H. (Hidemi), Iwata, H. (Hisato), Yatabe, Y. (Yasushi), Guénel, P. (Pascal), Truong, T. (Thérèse), Menegaux, F. (Florence), Sanchez, M. (Marie), Burwinkel, B. (Barbara), Marme, F. (Federick), Schneeweiss, A. (Andreas), Sohn, C. (Christof), Wu, A.H. (Anna H.), Tseng, C.-C. (Chiu-Chen), Van Den Berg, D. (David), Stram, D.O. (Daniel O.), Benítez, J. (Javier), Zamora, M.P. (Pilar), Perez, J.I.A. (Jose Ignacio Arias), Menéndez, P. (Primitiva), Shu, X.-O. (Xiao-Ou), Lu, W. (Wei), Gao, Y. (Ying), Cai, Q. (Qiuyin), Cox, A. (Angela), Cross, S.S. (Simon), Reed, M.W.R. (Malcolm), Andrulis, I.L. (Irene), Knight, J.A. (Julia), Glendon, G. (Gord), Tchatchou, S. (Sandrine), Sawyer, E.J. (Elinor), Tomlinson, I.P. (Ian), Kerin, M. (Michael), Miller, N. (Nicola), Haiman, C.A. (Christopher), Henderson, B.E. (Brian), Schumacher, F.R. (Fredrick), Le Marchand, L. (Loic), Lindblom, A. (Annika), Margolin, S. (Sara), Teo, S.-H. (Soo-Hwang), Yip, C.H. (Cheng Har), Lee, D.S.C. (Daphne S.C.), Wong, T.Y. (Tien Yin), Hooning, M.J. (Maartje), Martens, J.W.M. (John W. M.), Collée, J.M. (Margriet), Deurzen, C.H.M. (Carolien) van, Hopper, J.L. (John), Southey, M.C. (Melissa), Tsimiklis, H. (Helen), Kapuscinski, M.K. (Miroslav K.), Shen, C-Y. (Chen-Yang), Wu, P.-E. (Pei-Ei), Yu, J-C. (Jyh-Cherng), Chen, S.-T., Alnæs, G.G. (Grethe), Borresen-Dale, A.-L. (Anne-Lise), Giles, G.G. (Graham), Milne, R.L. (Roger), McLean, C.A. (Catriona Ann), Muir, K.R. (K.), Lophatananon, A. (Artitaya), Stewart-Brown, S. (Sarah), Siriwanarangsan, P. (Pornthep), Hartman, M. (Mikael), Miao, X., Buhari, S.A.B.S. (Shaik Ahmad Bin Syed), Teo, Y.Y. (Yik Ying), Fasching, P.A. (Peter), Haeberle, L. (Lothar), Ekici, A.B. (Arif), Beckmann, M.W. (Matthias), Brenner, H. (Hermann), Dieffenbach, A.K. (Aida Karina), Arndt, V. (Volker), Stegmaier, C. (Christa), Swerdlow, A.J. (Anthony ), Ashworth, A. (Alan), Orr, N. (Nick), Schoemaker, M. (Minouk), García-Closas, M. (Montserrat), Figueroa, J.D. (Jonine), Chanock, S.J. (Stephen), Lissowska, J. (Jolanta), Simard, J. (Jacques), Goldberg, M.S. (Mark), Labrèche, F. (France), Dumont, M. (Martine), Winqvist, R. (Robert), Pykäs, K. (Katri), Jukkola-Vuorinen, A. (Arja), Brauch, H. (Hiltrud), Brüning, T. (Thomas), Koto, Y.-D. (Yon-Dschun), Radice, P. (Paolo), Peterlongo, P. (Paolo), Bonnani, B. (Bernardo), Volorio, S. (Sara), Dörk, T. (Thilo), Bogdanova, N.V. (Natalia), Helbig, S. (Sonja), Mannermaa, A. (Arto), Kataja, V. (Vesa), Kosma, V-M. (Veli-Matti), Hartikainen, J.M. (J.), Devilee, P. (Peter), Tollenaar, R.A.E.M. (Rob), Seynaeve, C.M. (Caroline), Asperen, C.J. (Christi) van, Jakubowska, A. (Anna), Lubinski, J. (Jan), Jaworska-Bieniek, K. (Katarzyna), Durda, K. (Katarzyna), Slager, S. (Susan), Toland, A.E. (Amanda), Ambrosone, C.B. (Christine), Yannoukakos, D. (Drakoulis), Sangrajrang, S. (Suleeporn), Gaborieau, V. (Valerie), Brennan, P. (Paul), McKay, J.D. (James), Hamann, U. (Ute), Torres, D. (Diana), Zheng, W. (Wei), Long, J. (Jirong), Anton-Culver, H. (Hoda), Neuhausen, S.L. (Susan), Luccarini, C. (Craig), Baynes, C. (Caroline), Ahmed, S. (Shahana), Maranian, M. (Melanie), Healey, S. (Sue), González-Neira, A. (Anna), Pita, G. (Guillermo), Alonso, M.R. (Rosario), Álvarez, N. (Nuria), Herrero, D. (Daniel), Tessier, D.C. (Daniel C.), Vincent, D. (Daniel), Bacot, F. (Francois), Santiago, I. (Ines) de, Carroll, J. (Jason), Caldas, C. (Carlos), Brown, M. (Melissa), Lupien, M. (Mathieu), Kristensen, V. (Vessela), Pharoah, P.D.P. (Paul), Chenevix-Trench, G. (Georgia), French, J.D. (Juliet), Easton, D.F. (Douglas), Dunning, A.M. (Alison), Webb, P. (Penny), and De Fazio, A. (Anna)

Abstract

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10-43) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.

Published
2014
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13. Multiple nonglycemic genomic loci are newly associated with blood level of glycated hemoglobin in East Asians

Author

Chen, P. (Ping), Takeuchi, F. (Fumihiko), Lee, J.-Y. (Jong-Young), Li, H. (Huaixing), Wu, J.-Y. (Jer-Yuarn), Liang, J. (Jun), Long, J. (Jirong), Tabara, Y. (Yasuharu), Goodarzi, M. (Mark), Pereira, M.A. (Mark), Kim, Y.J., Go, M.J. (Min Jin), Stram, D.O. (Daniel), Vithana, E.N. (Eranga), Khor, C.C., Liu, J. (Jianjun), Liao, J. (Jie), Ye, X. (Xingwang), Wang, Y. (Yiqin), Lu, L., Young, T.L. (Terri), Lee, J.J.M. (Jeannette), Thai, A.C. (Ah Chuan), Cheng, C-Y. (Ching-Yu), Dam, R.M. (Rob) van, Friedlander, Y. (Yechiel), Heng, C.K. (Chew-Kiat), Koh, W.-P. (Woon-Puay), Chen, C.-H., Chang, L.-C. (Li-Ching), Pan, W.-H. (Wen-Harn), Qi, B. (Bin), Isono, M. (Masato), Zheng, W. (Wei), Cai, Q. (Qiuyin), Gao, Y. (Ying), Yamamoto, K. (Ken), Ohnaka, K. (Keizo), Takayanagi, R. (Ryoichi), Kita, Y. (Yoshikuni), Ueshima, H. (Hirotsugu), Hsiung, C.A. (Chao Agnes), Cui, J. (Jinrui), Sheu, W.H.-H. (Wayne), Rotter, J.I. (Jerome), Chen, Y.D.I. (Yii-Der Ida), Hsu, C. (Chris), Okada, Y. (Yukinori), Kubo, M. (Michiaki), Takahashi, A. (Atsushi), Tanaka, T. (Toshihiro), Rooij, F.J.A. (Frank) van, Ganesh, S.K. (Santhi), Huang, J. (Jian), Huang, T. (Tao), Yuan, J. (Jianmin), Hwang, J.-Y. (Joo-Yeon), Gross, M.D. (Myron), Assimes, T.L. (Themistocles), Miki, T. (Tetsuro), Shu, X.-O. (Xiao-Ou), Qi, L. (Lu), Chen, Y.T., Lin, X. (Xu), Aung, T. (Tin), Wong, T.Y. (Tien Yin), Teo, Y.Y. (Yik Ying), Kim, B.-J. (Bong-Jo), Kato, N. (Norihiro), Tai, E.-S. (E.-Shyong), Chen, P. (Ping), Takeuchi, F. (Fumihiko), Lee, J.-Y. (Jong-Young), Li, H. (Huaixing), Wu, J.-Y. (Jer-Yuarn), Liang, J. (Jun), Long, J. (Jirong), Tabara, Y. (Yasuharu), Goodarzi, M. (Mark), Pereira, M.A. (Mark), Kim, Y.J., Go, M.J. (Min Jin), Stram, D.O. (Daniel), Vithana, E.N. (Eranga), Khor, C.C., Liu, J. (Jianjun), Liao, J. (Jie), Ye, X. (Xingwang), Wang, Y. (Yiqin), Lu, L., Young, T.L. (Terri), Lee, J.J.M. (Jeannette), Thai, A.C. (Ah Chuan), Cheng, C-Y. (Ching-Yu), Dam, R.M. (Rob) van, Friedlander, Y. (Yechiel), Heng, C.K. (Chew-Kiat), Koh, W.-P. (Woon-Puay), Chen, C.-H., Chang, L.-C. (Li-Ching), Pan, W.-H. (Wen-Harn), Qi, B. (Bin), Isono, M. (Masato), Zheng, W. (Wei), Cai, Q. (Qiuyin), Gao, Y. (Ying), Yamamoto, K. (Ken), Ohnaka, K. (Keizo), Takayanagi, R. (Ryoichi), Kita, Y. (Yoshikuni), Ueshima, H. (Hirotsugu), Hsiung, C.A. (Chao Agnes), Cui, J. (Jinrui), Sheu, W.H.-H. (Wayne), Rotter, J.I. (Jerome), Chen, Y.D.I. (Yii-Der Ida), Hsu, C. (Chris), Okada, Y. (Yukinori), Kubo, M. (Michiaki), Takahashi, A. (Atsushi), Tanaka, T. (Toshihiro), Rooij, F.J.A. (Frank) van, Ganesh, S.K. (Santhi), Huang, J. (Jian), Huang, T. (Tao), Yuan, J. (Jianmin), Hwang, J.-Y. (Joo-Yeon), Gross, M.D. (Myron), Assimes, T.L. (Themistocles), Miki, T. (Tetsuro), Shu, X.-O. (Xiao-Ou), Qi, L. (Lu), Chen, Y.T., Lin, X. (Xu), Aung, T. (Tin), Wong, T.Y. (Tien Yin), Teo, Y.Y. (Yik Ying), Kim, B.-J. (Bong-Jo), Kato, N. (Norihiro), and Tai, E.-S. (E.-Shyong)

Abstract

Glycated hemoglobin A1c (HbA1c) is used as a measure of glycemic control and also as a diagnostic criterion for diabetes. To discover novel loci harboring common variants associated with HbA1c in East Asians, we conducted a meta-analysis of 13 genome-wide association studies (GWAS; N = 21,026). We replicated our findings in three additional studies comprising 11,576 individuals of East Asian ancestry. Ten variants showed associations that reached genome-wide significance in the discovery data set, of which nine (four novel variants at TMEM79 [ P value = 1.3 × 10 -23], HBS1L/MYB [8.5 × 10-15], MYO9B [9.0 × 10-12], and CYBA [1.1 × 10-8] as well as five variants at loci that had been previously identified [CDKAL1, G6PC2/ ABCB11, GCK, ANK1, and FN3KI]) showed consistent evidence of association in replication data sets. These variants explained 1.76% of the variance in HbA1c. Several of these variants (TMEM79, HBS1L/MYB, CYBA, MYO9B, ANK1, and FN3K) showed no association with either blood glucose or type 2 diabetes. Among individuals with nondiabetic levels of fasting glucose (<7.0 mmol/L) but elevated HbA1c (≥6.5%), 36.1% had HbA1c <6.5% after adjustment for these six variants. Our East Asian GWAS meta-analysis has identified novel variants associated with HbA1c as well as demonstrated that the effects of known variants are largely transferable across ethnic groups. Variants affecting erythrocyte parameters rather than glucose metabolism may be relevant to the use of HbA1c for diagnosing diabetes in these populations.

Published
2014
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14. Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)

Author

Canzian, F. Kaaks, R. Cox, D.G. Henderson, K.D. Henderson, B.E. Berg, C. Bingham, S. Boeing, H. Buring, J. Calle, E.E. Chanock, S. Clavel-Chapelon, F. Dossus, L. Feigelson, H.S. Haiman, C.A. Hankinson, S.E. Hoover, R. Hunter, D.J. Isaacs, C. Lenner, P. Lund, E. Overvad, K. Palli, D. Pearce, C.L. Quiros, J.R. Riboli, E. Stram, D.O. Thomas, G. Thun, M.J. Trichopoulos, D. van Gils, C.H. Ziegler, R.G.

Abstract

Background: Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3). Methods: We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects. Results: Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Conclusion: Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians. © 2009 Canzian et al; licensee BioMed Central Ltd.

Published
2009

15. Haplotypes of the estrogen receptor beta gene and breast cancer risk

Author

Cox, D.G. Bretsky, P. Kraft, P. Pharoah, P. Albanes, D. Altshuler, D. Amiano, P. Berglund, G. Boeing, H. Buring, J. Burtt, N. Calle, E.E. Canzian, F. Chanock, S. Clavel-Chapelon, F. Colditz, G.A. Feigelson, H.S. Haiman, C.A. Hankinson, S.E. Hirschhorn, J. Henderson, B.E. Hoover, R. Hunter, D.J. Kaaks, R. Kolonel, L. LeMarchand, L. Lund, E. Palli, D. Peeters, P.H.M. Pike, M.C. Riboli, E. Stram, D.O. Thun, M. Tjonneland, A. Travis, R.C. Trichopoulos, D. Yeager, M.

Abstract

Exposure to exogenous (oral contraceptives, postmenopausal hormone therapy) and endogenous (number of ovulatory cycles, adiposity) steroid hormones is associated with breast cancer risk. Breast cancer risk associated with these exposures could hypothetically be modified by genes in the steroid hormone synthesis, metabolism and signaling pathways. Estrogen receptors are the first step along the path of signaling cell growth and development upon stimulation with estrogens. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium has systematically selected haplotype tagging SNPs in genes along the steroid hormone synthesis, metabolism and binding pathways, including the estrogen receptor beta (ESR2) gene. Four htSNPs tag the 6 major (>5% frequency) haplotypes of the ESR2 gene. These polymorphisms have been genotyped in 5,789 breast cancer cases and 7,761 controls nested within the American Cancer Society Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study and Women's Health Study cohorts. None of the SNPs were independently associated with breast cancer risk. One haplotype of the ESR2 gene was associated with breast cancer risk before correction for multiple testing (OR 1.17, 95% CI 1.07-1.28, p = 0.0007). This haplotype remained associated with breast cancer risk after adjustment for multiple testing using a permutation procedure. There was no statistically significant heterogeneity in SNP or haplotype odds ratios across cohorts. These data suggest that inherited variants in ESR2 (while possibly conferring a small increased risk of breast cancer) are not associated with appreciable (OR > 1.2) changes in breast cancer risk among Caucasian women. © 2007 Wiley-Liss, Inc.

Published
2008

16. Genetic variation at the CYP19A1 locus predicts circulating estrogen levels but not breast cancer risk in postmenopausal women

Author

Haiman, C.A. Dossus, L. Setiawan, V.W. Stram, D.O. Dunning, A.M. Thomas, G. Thun, M.J. Albanes, D. Altshuler, D. Ardanaz, E. Boeing, H. Buring, J. Burtt, N. Calle, E.E. Chanock, S. Clavel-Chapelon, F. Colditz, G.A. Cox, D.G. Feigelson, H.S. Hankinson, S.E. Hayes, R.B. Henderson, B.E. Hirschhorn, J.N. Hoover, R. Hunter, D.J. Kaaks, R. Kolonel, L.N. Le Marchand, L. Lenner, P. Lund, E. Panico, S. Peeters, P.H. Pike, M.C. Riboli, E. Tjonneland, A. Travis, R. Trichopoulos, D. Wacholder, S. Ziegler, R.G.

Abstract

The CTP19A1 gene encodes the enzyme aromatase, which is responsible for the final step in the biosynthesis of estrogens. In this study, we used a systematic two-step approach that included gene resequencing and a haplotype-based analysis to comprehensively survey common genetic variation across the CYP19A1 locus in relation to circulating postmenopausal steroid hormone levels and breast cancer risk. This study was conducted among 5,356 invasive breast cancer cases and 7,129 controls comprised primarily of White women of European descent drawn from five large prospective cohorts within the National Cancer Institute Breast and Prostate Cancer Cohort Consortium. A high-density single-nucleotide polymorphism (SNP) map of 103 common SNPs (≥5% frequency) was used to identify the linkage disequilibrium and haplotype patterns across the CYP19A1 locus, and 19 haplotype-tagging SNPs were selected to provide high predictability of the common haplotype patterns. We found haplotype-tagging SNPs and common haplotypes spanning the coding and proximal 5′ region of CYP19A1 to be significantly associated with a 10% to 20% increase in endogenous estrogen levels in postmenopausal women [effect per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 4.4 × 10-15]. No significant associations were observed, however, with these SNPs or common haplotypes and breast cancer risk. Thus, although genetic variation in CYP19A1 produces measurable differences in estrogen levels among postmenopausal women, the magnitude of the change was insufficient to contribute detectably to breast cancer. ©2007 American Association for Cancer Research.

Published
2007

17. Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer

Author

Shen, H., Fridley, B.L., Song, H., Lawrenson, K., Cunningham, J.M., Ramus, S.J., Cicek, M.S., Tyrer, J., Stram, D., Larson, M.C., Kobel, M., Ziogas, A., Zheng, W., Yang, H.P., Wu, A.H., Wozniak, E.L., Ling Woo, Y., Winterhoff, B., Wik, E., Whittemore, A.S., Wentzensen, N., Palmieri Weber, R., Vitonis, A.F., Vincent, D., Vierkant, R.A., Vergote, I., Berg, D.P.G. van den, Altena, A.M. van, Tworoger, S.S., Thompson, P.J., Tessier, D.C., Terry, K.L., Teo, S.H., Templeman, C., Stram, D.O., Southey, M.C., Sieh, W., Siddiqui, N., Shvetsov, Y.B., Shu, X.O., Shridhar, V., Wang-Gohrke, S., Severi, G., Schwaab, I., Salvesen, H.B., Rzepecka, I.K., Runnebaum, I.B., Rossing, M.A., Rodriguez-Rodriguez, L., Risch, H.A., Renner, S.P., Poole, E.M., Pike, M.C., Phelan, C.M., Pelttari, L.M., Pejovic, T., Paul, J., Orlow, I., Zawiah Omar, S., Olson, S.H., Odunsi, K., Nickels, S., Nevanlinna, H., Ness, R.B., Narod, S.A., Nakanishi, T., Moysich, K.B., Monteiro, A.N., Moes-Sosnowska, J., Modugno, F., Menon, U., McLaughlin, J.R., McGuire, V., Matsuo, K., Mat Adenan, N.A., Massuger, L.F.A.G., Lurie, G., Lundvall, L., Lubinski, J., Lissowska, J., Levine, D.A., Leminen, A., Lee, A.W., Le, N.D., Lambrechts, S., Lambrechts, D., Kupryjanczyk, J., Krakstad, C., Konecny, G.E., Kruger Kjaer, S., Kiemeney, L.A.L.M., Kelemen, L.E., Keeney, G.L., Karlan, B.Y., Karevan, R., Kalli, K.R., Kajiyama, H., Ji, B.T., Jensen, A., Jakubowska, A., Iversen, E., Hosono, S., Hogdall, C.K., Hogdall, E., Hoatlin, M., Hillemans, P., Heitz, F., Hein, R., Harter, P., Halle, M.K., Hall, P., Gronwald, J., Gore, M., Goodman, M.T., Giles, G.G., Gentry-Maharaj, A., Garcia-Closas, M., Flanagan, J.M., Fasching, P.A., Ekici, A.B., Edwards, R., Eccles, D., Easton, D.F., Durst, M., Bois, A. du, Dork, T., Doherty, J.A., Despierre, E., Dansonka-Mieszkowska, A., Cybulski, C., Cramer, D.W, Cook, L.S., Chen, X., Charbonneau, B., Chang-Claude, J., Campbell, I., Butzow, R., Bunker, C.H., Brueggmann, D., Brown, R., Brooks-Wilson, A., Brinton, L.A., Bogdanova, N., Block, M.S., Benjamin, E., Beesley, J., Beckmann, M.W., Bandera, E.V., Baglietto, L., Bacot, F., Armasu, S.M., Antonenkova, N., Anton-Culver, H., Aben, K.K.H., Liang, D., et al., Shen, H., Fridley, B.L., Song, H., Lawrenson, K., Cunningham, J.M., Ramus, S.J., Cicek, M.S., Tyrer, J., Stram, D., Larson, M.C., Kobel, M., Ziogas, A., Zheng, W., Yang, H.P., Wu, A.H., Wozniak, E.L., Ling Woo, Y., Winterhoff, B., Wik, E., Whittemore, A.S., Wentzensen, N., Palmieri Weber, R., Vitonis, A.F., Vincent, D., Vierkant, R.A., Vergote, I., Berg, D.P.G. van den, Altena, A.M. van, Tworoger, S.S., Thompson, P.J., Tessier, D.C., Terry, K.L., Teo, S.H., Templeman, C., Stram, D.O., Southey, M.C., Sieh, W., Siddiqui, N., Shvetsov, Y.B., Shu, X.O., Shridhar, V., Wang-Gohrke, S., Severi, G., Schwaab, I., Salvesen, H.B., Rzepecka, I.K., Runnebaum, I.B., Rossing, M.A., Rodriguez-Rodriguez, L., Risch, H.A., Renner, S.P., Poole, E.M., Pike, M.C., Phelan, C.M., Pelttari, L.M., Pejovic, T., Paul, J., Orlow, I., Zawiah Omar, S., Olson, S.H., Odunsi, K., Nickels, S., Nevanlinna, H., Ness, R.B., Narod, S.A., Nakanishi, T., Moysich, K.B., Monteiro, A.N., Moes-Sosnowska, J., Modugno, F., Menon, U., McLaughlin, J.R., McGuire, V., Matsuo, K., Mat Adenan, N.A., Massuger, L.F.A.G., Lurie, G., Lundvall, L., Lubinski, J., Lissowska, J., Levine, D.A., Leminen, A., Lee, A.W., Le, N.D., Lambrechts, S., Lambrechts, D., Kupryjanczyk, J., Krakstad, C., Konecny, G.E., Kruger Kjaer, S., Kiemeney, L.A.L.M., Kelemen, L.E., Keeney, G.L., Karlan, B.Y., Karevan, R., Kalli, K.R., Kajiyama, H., Ji, B.T., Jensen, A., Jakubowska, A., Iversen, E., Hosono, S., Hogdall, C.K., Hogdall, E., Hoatlin, M., Hillemans, P., Heitz, F., Hein, R., Harter, P., Halle, M.K., Hall, P., Gronwald, J., Gore, M., Goodman, M.T., Giles, G.G., Gentry-Maharaj, A., Garcia-Closas, M., Flanagan, J.M., Fasching, P.A., Ekici, A.B., Edwards, R., Eccles, D., Easton, D.F., Durst, M., Bois, A. du, Dork, T., Doherty, J.A., Despierre, E., Dansonka-Mieszkowska, A., Cybulski, C., Cramer, D.W, Cook, L.S., Chen, X., Charbonneau, B., Chang-Claude, J., Campbell, I., Butzow, R., Bunker, C.H., Brueggmann, D., Brown, R., Brooks-Wilson, A., Brinton, L.A., Bogdanova, N., Block, M.S., Benjamin, E., Beesley, J., Beckmann, M.W., Bandera, E.V., Baglietto, L., Bacot, F., Armasu, S.M., Antonenkova, N., Anton-Culver, H., Aben, K.K.H., Liang, D., and et al.

Abstract

Contains fulltext : 118378.pdf (publisher's version ) (Open Access), HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.13, P=3.1 x 10(-10)) and clear cell (rs11651755 OR=0.77, P=1.6 x 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes.

Published
2013

18. Combined and Interactive Effects of Environmental and GWAS-Identified Risk Factors in Ovarian Cancer

Author

Pearce, C.L., Rossing, M.A., Lee, A.W., Ness, R.B., Webb, P.M., Chenevix-Trench, G., Jordan, S.M., Stram, D.A., Chang-Claude, J., Hein, R., Nickels, S., Lurie, G., Thompson, P.J., Carney, M.E., Goodman, M.T., Moysich, K., Hogdall, E., Jensen, A., Goode, E.L., Fridley, B.L., Cunningham, J.M., Vierkant, R.A., Weber, R.P., Ziogas, A., Anton-Culver, H., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Brinton, L., Wentzensen, N., Lissowska, J., Garcia-Closas, M., Massuger, L.F.A.G., Kiemeney, L.A.L.M., Altena, A.M. van, Aben, K.K.H., Berchuck, A., Doherty, J.A., Iversen, E., McGuire, V., Moorman, P.G., Pharoah, P., Pike, M.C., Risch, H., Sieh, W., Stram, D.O., Terry, K.L., Whittemore, A., Wu, A.H., Schildkraut, J.M., Kjaer, S.K., et al., Pearce, C.L., Rossing, M.A., Lee, A.W., Ness, R.B., Webb, P.M., Chenevix-Trench, G., Jordan, S.M., Stram, D.A., Chang-Claude, J., Hein, R., Nickels, S., Lurie, G., Thompson, P.J., Carney, M.E., Goodman, M.T., Moysich, K., Hogdall, E., Jensen, A., Goode, E.L., Fridley, B.L., Cunningham, J.M., Vierkant, R.A., Weber, R.P., Ziogas, A., Anton-Culver, H., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Brinton, L., Wentzensen, N., Lissowska, J., Garcia-Closas, M., Massuger, L.F.A.G., Kiemeney, L.A.L.M., Altena, A.M. van, Aben, K.K.H., Berchuck, A., Doherty, J.A., Iversen, E., McGuire, V., Moorman, P.G., Pharoah, P., Pike, M.C., Risch, H., Sieh, W., Stram, D.O., Terry, K.L., Whittemore, A., Wu, A.H., Schildkraut, J.M., Kjaer, S.K., and et al.

Abstract

Contains fulltext : 118172.pdf (publisher's version ) (Closed access), BACKGROUND: There are several well-established environmental risk factors for ovarian cancer, and recent genome-wide association studies have also identified six variants that influence disease risk. However, the interplay between such risk factors and susceptibility loci has not been studied. METHODS: Data from 14 ovarian cancer case-control studies were pooled, and stratified analyses by each environmental risk factor with tests for heterogeneity were conducted to determine the presence of interactions for all histologic subtypes. A genetic "risk score" was created to consider the effects of all six variants simultaneously. A multivariate model was fit to examine the association between all environmental risk factors and genetic risk score on ovarian cancer risk. RESULTS: Among 7,374 controls and 5,566 cases, there was no statistical evidence of interaction between the six SNPs or genetic risk score and the environmental risk factors on ovarian cancer risk. In a main effects model, women in the highest genetic risk score quartile had a 65% increased risk of ovarian cancer compared with women in the lowest [95% confidence interval (CI), 1.48-1.84]. Analyses by histologic subtype yielded risk differences across subtype for endometriosis (Phet < 0.001), parity (Phet < 0.01), and tubal ligation (Phet = 0.041). CONCLUSIONS: The lack of interactions suggests that a multiplicative model is the best fit for these data. Under such a model, we provide a robust estimate of the effect of each risk factor that sets the stage for absolute risk prediction modeling that considers both environmental and genetic risk factors. Further research into the observed differences in risk across histologic subtype is warranted. Cancer Epidemiol Biomarkers Prev; 22(5); 880-90. (c)2013 AACR.

Published
2013

19. The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing

Author

Pharoah, P.D., Palmieri, R.T., Ramus, S.J., Gayther, S.A., Andrulis, I.L., Anton-Culver, H., Antonenkova, N., Antoniou, A.C., Goldgar, D., Beattie, M.S., Beckmann, M.W., Birrer, M.J., Bogdanova, N., Bolton, K.L., Brewster, W., Brooks-Wilson, A., Brown, R., Butzow, R., Caldes, T., Caligo, M.A., Campbell, I., Chang-Claude, J., Chen, Y.A., Cook, L.S., Couch, F.J., Cramer, D.W, Cunningham, J.M., Despierre, E., Doherty, J.A., Dork, T., Durst, M., Eccles, D.M., Ekici, A.B., Easton, D., Fasching, P.A., Fazio, A. de, Fenstermacher, D.A., Flanagan, J.M., Fridley, B.L., Friedman, E., Gao, B., Sinilnikova, O., Gentry-Maharaj, A., Godwin, A.K., Goode, E.L., Goodman, M.T., Gross, J., Hansen, T.V., Harnett, P., Rookus, M., Heikkinen, T., Hein, R., Hogdall, C., Hogdall, E., Iversen, E.S., Jakubowska, A., Johnatty, S.E., Karlan, B.Y., Kauff, N.D., Kaye, S.B., Chenevix-Trench, G., Kelemen, L.E., Kiemeney, L.A.L.M., Kjaer, S.K., Lambrechts, D., Lapolla, J.P., Lazaro, C., Le, N.D., Leminen, A., Leunen, K., Levine, D.A., Lu, Y., Lundvall, L., MacGregor, S., Marees, T., Massuger, L.F.A.G., McLaughlin, J.R., Menon, U., Montagna, M., Moysich, K.B., Narod, S.A., Nathanson, K.L., Nedergaard, L., Ness, R.B., Nevanlinna, H., Nickels, S., Osorio, A., Paul, J., Pearce, C.L., Phelan, C.M., Pike, M.C., Radice, P., Rossing, M.A., Schildkraut, J.M., Sellers, T.A., Singer, C.F., Song, H., Stram, D.O., Sutphen, R., Lindblom, A., et al., Pharoah, P.D., Palmieri, R.T., Ramus, S.J., Gayther, S.A., Andrulis, I.L., Anton-Culver, H., Antonenkova, N., Antoniou, A.C., Goldgar, D., Beattie, M.S., Beckmann, M.W., Birrer, M.J., Bogdanova, N., Bolton, K.L., Brewster, W., Brooks-Wilson, A., Brown, R., Butzow, R., Caldes, T., Caligo, M.A., Campbell, I., Chang-Claude, J., Chen, Y.A., Cook, L.S., Couch, F.J., Cramer, D.W, Cunningham, J.M., Despierre, E., Doherty, J.A., Dork, T., Durst, M., Eccles, D.M., Ekici, A.B., Easton, D., Fasching, P.A., Fazio, A. de, Fenstermacher, D.A., Flanagan, J.M., Fridley, B.L., Friedman, E., Gao, B., Sinilnikova, O., Gentry-Maharaj, A., Godwin, A.K., Goode, E.L., Goodman, M.T., Gross, J., Hansen, T.V., Harnett, P., Rookus, M., Heikkinen, T., Hein, R., Hogdall, C., Hogdall, E., Iversen, E.S., Jakubowska, A., Johnatty, S.E., Karlan, B.Y., Kauff, N.D., Kaye, S.B., Chenevix-Trench, G., Kelemen, L.E., Kiemeney, L.A.L.M., Kjaer, S.K., Lambrechts, D., Lapolla, J.P., Lazaro, C., Le, N.D., Leminen, A., Leunen, K., Levine, D.A., Lu, Y., Lundvall, L., MacGregor, S., Marees, T., Massuger, L.F.A.G., McLaughlin, J.R., Menon, U., Montagna, M., Moysich, K.B., Narod, S.A., Nathanson, K.L., Nedergaard, L., Ness, R.B., Nevanlinna, H., Nickels, S., Osorio, A., Paul, J., Pearce, C.L., Phelan, C.M., Pike, M.C., Radice, P., Rossing, M.A., Schildkraut, J.M., Sellers, T.A., Singer, C.F., Song, H., Stram, D.O., Sutphen, R., Lindblom, A., and et al.

Abstract

Contains fulltext : 98456.pdf (publisher's version ) (Closed access), PURPOSE: An assay for the single-nucleotide polymorphism (SNP), rs61764370, has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3'-UTR miRNA binding site of the KRAS oncogene and is a candidate for epithelial ovarian cancer (EOC) susceptibility. However, only one published article, analyzing fewer than 1,000 subjects in total, has examined this association. EXPERIMENTAL DESIGN: Risk association was evaluated in 8,669 cases of invasive EOC and 10,012 controls from 19 studies participating in the Ovarian Cancer Association Consortium, and in 683 cases and 2,044 controls carrying BRCA1 mutations from studies in the Consortium of Investigators of Modifiers of BRCA1/2. Prognosis association was also examined in a subset of five studies with progression-free survival (PFS) data and 18 studies with all-cause mortality data. RESULTS: No evidence of association was observed between genotype and risk of unselected EOC (OR = 1.02, 95% CI: 0.95-1.10), serous EOC (OR = 1.08, 95% CI: 0.98-1.18), familial EOC (OR = 1.09, 95% CI: 0.78-1.54), or among women carrying deleterious mutations in BRCA1 (OR = 1.09, 95% CI: 0.88-1.36). There was little evidence for association with survival time among unselected cases (HR = 1.10, 95% CI: 0.99-1.22), among serous cases (HR = 1.12, 95% CI = 0.99-1.28), or with PFS in 540 cases treated with carboplatin and paclitaxel (HR = 1.18, 95% CI: 0.93-1.52). CONCLUSIONS: These data exclude the possibility of an association between rs61764370 and a clinically significant risk of ovarian cancer or of familial ovarian cancer. Use of this SNP for ovarian cancer clinical risk prediction, therefore, seems unwarranted.

Published
2011

20. Common variants at 19p13 are associated with susceptibility to ovarian cancer.

Author

Bolton, K.L., Tyrer, J.P., Song, H., Ramus, S.J., Notaridou, M., Jones, C., Sher, T., Gentry-Maharaj, A., Wozniak, E., Tsai, Y.Y., Weidhaas, J., Paik, D., Berg, D.P.G. van den, Stram, D.O., Pearce, C.L., Wu, A.H., Brewster, W., Anton-Culver, H., Ziogas, A., Narod, S., Levine, D.A., Kaye, S.B., Brown, R., Paul, J., Flanagan, J., Sieh, W., McGuire, V., Whittemore, A.S., Campbell, I., Gore, M.E., Lissowska, J., Yang, H.P., Medrek, K., Gronwald, J., Lubinski, J., Jakubowska, A., Le, N.D., Cook, L.S., Keleman, L.E., Brook-Wilson, A., Massuger, L.F.A.G., Kiemeney, L.A.L.M., Aben, K.K.H., Altena, A.M. van, Houlston, R.S., Tomlinson, I., Palmieri, R.T., Moorman, P.G., Schildkraut, J., Iversen, E.S., Phelan, C.M., Vierkant, R.A., Cunningham, J.M., Goode, E.L., Fridley, B.L., Kruger-Kjaer, S., Blaeker, J., Hogdall, E., Hogdall, C., Gross, J., Karlan, B.Y., Ness, R.B., Edwards, R.P., Odunsi, K., Moyisch, K.B., Baker, J.A., Modugno, F., Heikkinenen, T., Butzow, R., Nevanlinna, H., Leminen, A., Bogdanova, N., Antonenkova, N., Doerk, T., Hillemanns, P., Durst, M., Runnebaum, I., Thompson, P.J., Carney, M.E., Goodman, M.T., Lurie, G., Wang-Gohrke, S., Hein, R., Chang-Claude, J., Rossing, M.A., Cushing-Haugen, K.L., Doherty, J., Chen, C., Rafnar, T., Besenbacher, S., Sulem, P., Stefansson, K., Birrer, M.J., Bolton, K.L., Tyrer, J.P., Song, H., Ramus, S.J., Notaridou, M., Jones, C., Sher, T., Gentry-Maharaj, A., Wozniak, E., Tsai, Y.Y., Weidhaas, J., Paik, D., Berg, D.P.G. van den, Stram, D.O., Pearce, C.L., Wu, A.H., Brewster, W., Anton-Culver, H., Ziogas, A., Narod, S., Levine, D.A., Kaye, S.B., Brown, R., Paul, J., Flanagan, J., Sieh, W., McGuire, V., Whittemore, A.S., Campbell, I., Gore, M.E., Lissowska, J., Yang, H.P., Medrek, K., Gronwald, J., Lubinski, J., Jakubowska, A., Le, N.D., Cook, L.S., Keleman, L.E., Brook-Wilson, A., Massuger, L.F.A.G., Kiemeney, L.A.L.M., Aben, K.K.H., Altena, A.M. van, Houlston, R.S., Tomlinson, I., Palmieri, R.T., Moorman, P.G., Schildkraut, J., Iversen, E.S., Phelan, C.M., Vierkant, R.A., Cunningham, J.M., Goode, E.L., Fridley, B.L., Kruger-Kjaer, S., Blaeker, J., Hogdall, E., Hogdall, C., Gross, J., Karlan, B.Y., Ness, R.B., Edwards, R.P., Odunsi, K., Moyisch, K.B., Baker, J.A., Modugno, F., Heikkinenen, T., Butzow, R., Nevanlinna, H., Leminen, A., Bogdanova, N., Antonenkova, N., Doerk, T., Hillemanns, P., Durst, M., Runnebaum, I., Thompson, P.J., Carney, M.E., Goodman, M.T., Lurie, G., Wang-Gohrke, S., Hein, R., Chang-Claude, J., Rossing, M.A., Cushing-Haugen, K.L., Doherty, J., Chen, C., Rafnar, T., Besenbacher, S., Sulem, P., Stefansson, K., and Birrer, M.J.

Abstract

Contains fulltext : 89441.pdf (publisher's version ) (Closed access)

Published
2010

21. A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24.

Author

Goode, E.L., Chenevix-Trench, G., Song, H., Ramus, S.J., Notaridou, M., Lawrenson, K., Widschwendter, M., Vierkant, R.A., Larson, M.C., Kjaer, S.K., Birrer, M.J., Berchuck, A., Schildkraut, J., Tomlinson, I.P., Kiemeney, L.A.L.M., Cook, L.S., Gronwald, J., Garcia-Closas, M., Gore, M.E., Campbell, I., Whittemore, A.S., Sutphen, R., Phelan, C.M., Anton-Culver, H., Pearce, C.L., Lambrechts, D., Rossing, M.A., Chang-Claude, J., Moysich, K.B., Goodman, M.T., Dork, T., Nevanlinna, H., Ness, R.B., Rafnar, T., Hogdall, E., Fridley, B.L., Cunningham, J.M., Sieh, W., McGuire, V., Godwin, A.K., Cramer, D.W, Hernandez, D., Levine, D., Lu, K., Iversen, E.S., Palmieri, R.T., Houlston, R.S., Altena, A.M. van, Aben, K.K.H., Massuger, L.F.A.G., Brooks-Wilson, A., Kelemen, L.E., Le, N.D., Jakubowska, A., Lubinski, J., Medrek, K., Stafford, A., Easton, D.F., Tyrer, J.P., Bolton, K.L., Harrington, P., Eccles, D., Chen, A., Molina, A.N., Davila, B.N., Arango, H., Tsai, Y.Y., Chen, Z., Risch, H.A., McLaughlin, J., Narod, S., Ziogas, A., Brewster, W., Gentry-Maharaj, A., Menon, U., Wu, A.H., Stram, D.O., Pike, M.C., Beesley, J., Webb, P.M., Chen, X., Ekici, A.B., Thiel, F.C., Beckmann, M.W., Yang, H., Wentzensen, N., Lissowska, J., Fasching, P.A., Despierre, E., Amant, F., Vergote, I., Doherty, J., Hein, R., Wang-Gohrke, S., Lurie, G., Carney, M.E., Thompson, P., Goode, E.L., Chenevix-Trench, G., Song, H., Ramus, S.J., Notaridou, M., Lawrenson, K., Widschwendter, M., Vierkant, R.A., Larson, M.C., Kjaer, S.K., Birrer, M.J., Berchuck, A., Schildkraut, J., Tomlinson, I.P., Kiemeney, L.A.L.M., Cook, L.S., Gronwald, J., Garcia-Closas, M., Gore, M.E., Campbell, I., Whittemore, A.S., Sutphen, R., Phelan, C.M., Anton-Culver, H., Pearce, C.L., Lambrechts, D., Rossing, M.A., Chang-Claude, J., Moysich, K.B., Goodman, M.T., Dork, T., Nevanlinna, H., Ness, R.B., Rafnar, T., Hogdall, E., Fridley, B.L., Cunningham, J.M., Sieh, W., McGuire, V., Godwin, A.K., Cramer, D.W, Hernandez, D., Levine, D., Lu, K., Iversen, E.S., Palmieri, R.T., Houlston, R.S., Altena, A.M. van, Aben, K.K.H., Massuger, L.F.A.G., Brooks-Wilson, A., Kelemen, L.E., Le, N.D., Jakubowska, A., Lubinski, J., Medrek, K., Stafford, A., Easton, D.F., Tyrer, J.P., Bolton, K.L., Harrington, P., Eccles, D., Chen, A., Molina, A.N., Davila, B.N., Arango, H., Tsai, Y.Y., Chen, Z., Risch, H.A., McLaughlin, J., Narod, S., Ziogas, A., Brewster, W., Gentry-Maharaj, A., Menon, U., Wu, A.H., Stram, D.O., Pike, M.C., Beesley, J., Webb, P.M., Chen, X., Ekici, A.B., Thiel, F.C., Beckmann, M.W., Yang, H., Wentzensen, N., Lissowska, J., Fasching, P.A., Despierre, E., Amant, F., Vergote, I., Doherty, J., Hein, R., Wang-Gohrke, S., Lurie, G., Carney, M.E., and Thompson, P.

Abstract

Contains fulltext : 89180.pdf (publisher's version ) (Closed access)

Published
2010

22. Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics

Author

García-Closas, M. (Montserrat), Hall, P. (Per), Nevanlinna, H. (Heli), Pooley, K.A. (Karen), Morrison, J. (Jonathan), Richesson, D.A. (Douglas), Bojesen, S.E. (Stig), Nordestgaard, B.G. (Børge), Axelsson, C.K. (Christen), Arias Pérez, J.I. (José Ignacio), Milne, R.L. (Roger), Ribas, G. (Gloria), González-Neira, A. (Anna), Benítez, J. (Javier), Zamora, P. (Pilar), Brauch, H. (Hiltrud), Justenhoven, C. (Christina), Hamann, U. (Ute), Ko, Y-D. (Yon-Dschun), Bruening, T. (Thomas), Haas, S. (Susanne), Dörk, T. (Thilo), Schürmann, P. (Peter), Hillemanns, P. (Peter), Bogdanova, N.V. (Natalia), Bremer, M. (Michael), Karstens, J.H. (Johann), Fagerholm, R. (Rainer), Aaltonen, K. (Kirsimari), Aittomäki, K. (Kristiina), Smitten, K. (Karl) von, Blomqvist, C. (Carl), Mannermaa, A. (Arto), Uusitupa, M. (Matti), Eskelinen, M. (Matti), Tengström, M. (Maria), Kosma, V-M. (Veli-Matti), Kataja, V. (Vesa), Chenevix-Trench, G. (Georgia), Spurdle, A.B. (Amanda), Beesley, J. (Jonathan), Chen, X. (Xiaoqing), Devilee, P. (Peter), Asperen, C.J. (Christi) van, Jacobi, C.E. (Catharina), Tollenaar, R.A.E.M. (Rob), Huijts, P. (Petra), Klijn, J.G.M. (Jan), Chang-Claude, J. (Jenny), Kropp, S. (Silke), Slanger, T. (Tracy), Flesch-Janys, D. (Dieter), Mutschelknauss, E. (Elke), Salazar, R. (Ramona), Wang-Gohrke, S. (Shan), Couch, F.J. (Fergus), Goode, E.L. (Ellen), Olson, J.E. (Janet), Vachon, C. (Celine), Fredericksen, Z. (Zachary), Giles, G.G. (Graham), Baglietto, L. (Laura), Severi, G. (Gianluca), Hopper, J.L. (John), English, D.R. (Dallas), Southey, M.C. (Melissa), Haiman, C.A. (Christopher), Henderson, B.E. (Brian), Kolonel, L.N. (Laurence), Le Marchand, L. (Loic), Stram, D.O. (Daniel), Hunter, D. (David), Hankinson, S.E. (Susan), Cox, A. (Angela), Tamimi, R. (Rulla), Kraft, P. (Peter), Sherman, M.E. (Mark), Chanock, S.J. (Stephen), Lissowska, J. (Jolanta), Brinton, L.A. (Louise), Peplonska, B. (Beata), Hooning, M.J. (Maartje), Meijers-Heijboer, E.J. (Hanne), Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Uitterlinden, A.G. (André), Liu, J. (Jianjun), Low, Y.L., Yuqing, L. (Li), Humphreys, M.K. (Manjeet), Czene, K. (Kamila), Balasubramanian, S. (Sabapathy), Cross, S.S. (Simon), Reed, M.W.R. (Malcolm), Blows, F. (Fiona), Driver, K. (Kristy), Dunning, A.M. (Alison), Tyrer, J.P. (Jonathan), Ponder, B.A.J. (Bruce), Sangrajrang, S. (Suleeporn), Brennan, P. (Paul), McKay, J.D. (James), Odefrey, F. (Fabrice), Gabrieau, V. (Valerie), Sigurdson, A.J. (Alice), Doody, M. (Michele), Struewing, J.P. (Jeffrey), Alexander, B.H. (Bruce), Easton, D.F. (Douglas), Pharoah, P.D.P. (Paul), García-Closas, M. (Montserrat), Hall, P. (Per), Nevanlinna, H. (Heli), Pooley, K.A. (Karen), Morrison, J. (Jonathan), Richesson, D.A. (Douglas), Bojesen, S.E. (Stig), Nordestgaard, B.G. (Børge), Axelsson, C.K. (Christen), Arias Pérez, J.I. (José Ignacio), Milne, R.L. (Roger), Ribas, G. (Gloria), González-Neira, A. (Anna), Benítez, J. (Javier), Zamora, P. (Pilar), Brauch, H. (Hiltrud), Justenhoven, C. (Christina), Hamann, U. (Ute), Ko, Y-D. (Yon-Dschun), Bruening, T. (Thomas), Haas, S. (Susanne), Dörk, T. (Thilo), Schürmann, P. (Peter), Hillemanns, P. (Peter), Bogdanova, N.V. (Natalia), Bremer, M. (Michael), Karstens, J.H. (Johann), Fagerholm, R. (Rainer), Aaltonen, K. (Kirsimari), Aittomäki, K. (Kristiina), Smitten, K. (Karl) von, Blomqvist, C. (Carl), Mannermaa, A. (Arto), Uusitupa, M. (Matti), Eskelinen, M. (Matti), Tengström, M. (Maria), Kosma, V-M. (Veli-Matti), Kataja, V. (Vesa), Chenevix-Trench, G. (Georgia), Spurdle, A.B. (Amanda), Beesley, J. (Jonathan), Chen, X. (Xiaoqing), Devilee, P. (Peter), Asperen, C.J. (Christi) van, Jacobi, C.E. (Catharina), Tollenaar, R.A.E.M. (Rob), Huijts, P. (Petra), Klijn, J.G.M. (Jan), Chang-Claude, J. (Jenny), Kropp, S. (Silke), Slanger, T. (Tracy), Flesch-Janys, D. (Dieter), Mutschelknauss, E. (Elke), Salazar, R. (Ramona), Wang-Gohrke, S. (Shan), Couch, F.J. (Fergus), Goode, E.L. (Ellen), Olson, J.E. (Janet), Vachon, C. (Celine), Fredericksen, Z. (Zachary), Giles, G.G. (Graham), Baglietto, L. (Laura), Severi, G. (Gianluca), Hopper, J.L. (John), English, D.R. (Dallas), Southey, M.C. (Melissa), Haiman, C.A. (Christopher), Henderson, B.E. (Brian), Kolonel, L.N. (Laurence), Le Marchand, L. (Loic), Stram, D.O. (Daniel), Hunter, D. (David), Hankinson, S.E. (Susan), Cox, A. (Angela), Tamimi, R. (Rulla), Kraft, P. (Peter), Sherman, M.E. (Mark), Chanock, S.J. (Stephen), Lissowska, J. (Jolanta), Brinton, L.A. (Louise), Peplonska, B. (Beata), Hooning, M.J. (Maartje), Meijers-Heijboer, E.J. (Hanne), Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Uitterlinden, A.G. (André), Liu, J. (Jianjun), Low, Y.L., Yuqing, L. (Li), Humphreys, M.K. (Manjeet), Czene, K. (Kamila), Balasubramanian, S. (Sabapathy), Cross, S.S. (Simon), Reed, M.W.R. (Malcolm), Blows, F. (Fiona), Driver, K. (Kristy), Dunning, A.M. (Alison), Tyrer, J.P. (Jonathan), Ponder, B.A.J. (Bruce), Sangrajrang, S. (Suleeporn), Brennan, P. (Paul), McKay, J.D. (James), Odefrey, F. (Fabrice), Gabrieau, V. (Valerie), Sigurdson, A.J. (Alice), Doody, M. (Michele), Struewing, J.P. (Jeffrey), Alexander, B.H. (Bruce), Easton, D.F. (Douglas), and Pharoah, P.D.P. (Paul)

Abstract

A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10-13). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10-5, 10-8, 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10-4, respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the eti

Published
2008
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23. Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the Ovarian Cancer Association Consortium pooled analysis

Author

Pearce, C.L., Wu, A.H., Gayther, S.A., Bale, A.E., Beck, P.A., Beesley, J., Chanock, S., Cramer, D.W., DiCioccio, R., Edwards, R., Fredericksen, Z.S., Garcia-Closas, M., Goode, E.L., Green, A.C., Hartmann, L.C., Kjaer, S.K., Lissowska, J., McGuire, V., Modugno, F., Moysich, K., Ness, R.B., Ramus, S.J., Risch, H.A., Sellers, T.A., Song, H., Stram, D.O., Terry, K.L., Webb, P.M., Whiteman, D.C., Whittemore, A.S., Zheng, W., Pharoah, P.D., Chenevix-Trench, G., Pike, M.C., Schildkraut, J., Berchuck, A., Høgdall, Estrid Vilma Solyom, Pearce, C.L., Wu, A.H., Gayther, S.A., Bale, A.E., Beck, P.A., Beesley, J., Chanock, S., Cramer, D.W., DiCioccio, R., Edwards, R., Fredericksen, Z.S., Garcia-Closas, M., Goode, E.L., Green, A.C., Hartmann, L.C., Kjaer, S.K., Lissowska, J., McGuire, V., Modugno, F., Moysich, K., Ness, R.B., Ramus, S.J., Risch, H.A., Sellers, T.A., Song, H., Stram, D.O., Terry, K.L., Webb, P.M., Whiteman, D.C., Whittemore, A.S., Zheng, W., Pharoah, P.D., Chenevix-Trench, G., Pike, M.C., Schildkraut, J., Berchuck, A., and Høgdall, Estrid Vilma Solyom

Abstract

There is evidence that progesterone plays a role in the aetiology of invasive epithelial ovarian cancer. Therefore, genes involved in pathways that regulate progesterone may be candidates for susceptibility to this disease. Previous studies have suggested that genetic variants in the progesterone receptor gene (PGR) may be associated with ovarian cancer risk, although results have been inconsistent. We have established an international consortium to pool resources and data from many ovarian cancer case-control studies in an effort to identify variants that influence risk. In this study, three PGR single nucleotide polymorphisms (SNPs), for which previous data have suggested they affect ovarian cancer risk, were examined. These were +331 C/T (rs10895068), PROGINS (rs1042838), and a 3' variant (rs608995). A total of 4788 ovarian cancer cases and 7614 controls from 12 case-control studies were included in this analysis. Unconditional logistic regression was used to model the association between each SNP and ovarian cancer risk and two-sided P-values are reported. Overall, risk of ovarian cancer was not associated with any of the three variants studied. However, in histopathological subtype analyses, we found a statistically significant association between risk of endometrioid ovarian cancer and the PROGINS allele (n=651, OR=1.17, 95% CI=1.01-1.36, P=0.036). We also observed borderline evidence of an association between risk of endometrioid ovarian cancer and the +331C/T variant (n=725 cases; OR=0.80, 95% CI 0.62-1.04, P=0.100). These data suggest that while these three variants in the PGR are not associated with ovarian cancer overall, the PROGINS variant may play a modest role in risk of endometrioid ovarian cancer Udgivelsesdato: 2008/1/29

Published
2008

24. Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics

Author

Garcia-Closas, M., Hall, P., Nevanlinna, H., Pooley, K., Morrison, J., Richesson, D.A., Bojesen, S.E., Axelsson, C.K., Arias, J.I., Milne, R.L., Ribas, G., Gonzalez-Neira, A., Benitez, J., Zamora, P., Brauch, H., Justenhoven, C., Hamann, U., Ko, Y.D., Bruening, T., Haas, S., Dork, T., Schurmann, P., Hillemanns, P., Bogdanova, N., Bremer, M., Karstens, J.H., Fagerholm, R., Aaltonen, K., Aittomaki, K., Smitten, K. Von, Blomqvist, C., Mannermaa, A., Uusitupa, M., Eskelinen, M., Tengstrom, M., Kosma, V.M., Kataja, V., Chenevix-Trench, G., Spurdle, A.B., Beesley, J., Chen, X., Devilee, P., Asperen, C.J. Van, Jacobi, C.E., Tollenaar, R.A.E.M., Huijts, P.E.A., Klijn, J.G.M., Chang-Claude, J., Kropp, S., Slanger, T., Flesch-Janys, D., Mutschelknauss, E., Salazar, R., Wang-Gohrke, S., Couch, F., Goode, E.L., Olson, J.E., Vachon, C., Fredericksen, Z.S., Giles, G.G., Baglietto, L., Severi, G., Hopper, J.L., English, D.R., Southey, M.C., Haiman, C.A., Henderson, B.E., Kolonel, L.N., Marchand, L. Le, Stram, D.O., Hunter, D.J., Hankinson, S.E., Cox, D.G., Tamimi, R., Kraft, P., Sherman, M.E., Chanock, S.J., Lissowska, J., Brinton, L.A., Peplonska, B., Hooning, M.J., Meijers-Heijboer, H., Collee, J.M., Ouweland, A. Van den, Uitterlinden, A.G., Liu, J., Lin, L.Y., Yuqing, L., Humphreys, K., Czene, K., Cox, A., Balasubramanian, S.P., Cross, S.S., Reed, M.W.R., Blows, F., Driver, K., Dunning, A., Tyrer, J., Ponder, B.A.J., Sangrajrang, S., Brennan, P., Mckay, J., Odefrey, F., Gabrieau, V., Sigurdson, A., Doody, M., Struewing, J.P., Alexander, B., Easton, D.F., Pharoah, P.D., Nordestgaard, Børge, Garcia-Closas, M., Hall, P., Nevanlinna, H., Pooley, K., Morrison, J., Richesson, D.A., Bojesen, S.E., Axelsson, C.K., Arias, J.I., Milne, R.L., Ribas, G., Gonzalez-Neira, A., Benitez, J., Zamora, P., Brauch, H., Justenhoven, C., Hamann, U., Ko, Y.D., Bruening, T., Haas, S., Dork, T., Schurmann, P., Hillemanns, P., Bogdanova, N., Bremer, M., Karstens, J.H., Fagerholm, R., Aaltonen, K., Aittomaki, K., Smitten, K. Von, Blomqvist, C., Mannermaa, A., Uusitupa, M., Eskelinen, M., Tengstrom, M., Kosma, V.M., Kataja, V., Chenevix-Trench, G., Spurdle, A.B., Beesley, J., Chen, X., Devilee, P., Asperen, C.J. Van, Jacobi, C.E., Tollenaar, R.A.E.M., Huijts, P.E.A., Klijn, J.G.M., Chang-Claude, J., Kropp, S., Slanger, T., Flesch-Janys, D., Mutschelknauss, E., Salazar, R., Wang-Gohrke, S., Couch, F., Goode, E.L., Olson, J.E., Vachon, C., Fredericksen, Z.S., Giles, G.G., Baglietto, L., Severi, G., Hopper, J.L., English, D.R., Southey, M.C., Haiman, C.A., Henderson, B.E., Kolonel, L.N., Marchand, L. Le, Stram, D.O., Hunter, D.J., Hankinson, S.E., Cox, D.G., Tamimi, R., Kraft, P., Sherman, M.E., Chanock, S.J., Lissowska, J., Brinton, L.A., Peplonska, B., Hooning, M.J., Meijers-Heijboer, H., Collee, J.M., Ouweland, A. Van den, Uitterlinden, A.G., Liu, J., Lin, L.Y., Yuqing, L., Humphreys, K., Czene, K., Cox, A., Balasubramanian, S.P., Cross, S.S., Reed, M.W.R., Blows, F., Driver, K., Dunning, A., Tyrer, J., Ponder, B.A.J., Sangrajrang, S., Brennan, P., Mckay, J., Odefrey, F., Gabrieau, V., Sigurdson, A., Doody, M., Struewing, J.P., Alexander, B., Easton, D.F., Pharoah, P.D., and Nordestgaard, Børge

Abstract

A three-stage genome-wide association study recently identified single nucleotide polymorphisms ( SNPs) in five loci ( fibroblast growth receptor 2 ( FGFR2), trinucleotide repeat containing 9 ( TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte- specific protein 1 ( LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER- positive ( per- allele OR ( 95%CI) = 1.31 (1.27-1.36)) than ER- negative (1.08 (1.03- 1.14)) disease ( P for heterogeneity = 10-(13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER- positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs ( rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER- negative disease, the strongest association being for rs3803662 in TNRC9 ( 1.14 ( 1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis ( per- allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER- positive and ER- negative disease are biologically d

Published
2008

25. Haplotype analysis of the HSD17B1 gene and risk of breast cancer: a comprehensive approach to multicenter analyses of prospective cohort studies.

Author

Feigelson, H.S., Cox, D.G., Cann, H.M., Wacholder, S., Kaaks, R., Henderson, B.E., Albanes, D., Altshuler, D., Berglund, G., Berrino, F., Bingham, S, Buring, J.E., Burtt, N.P., Calle, E.E., Chanock, S.J., Clavel-Chapelon, F., Colditz, G., Diver, W.R., Freedman, M.L., Haiman, C.A., Hankinson, S.E., Hayes, R.B., Hirschhorn, J.N., Hunter, D., Kolonel, L.N., Kraft, P., LeMarchand, L., Linseisen, J., Modi, W., Navarro, C., Peeters, P.H.M., Pike, M.C., Riboli, E., Setiawan, V.W., Stram, D.O., Thomas, G., Thun, M.J., Tjonneland, A., Trichopoulos, D., Feigelson, H.S., Cox, D.G., Cann, H.M., Wacholder, S., Kaaks, R., Henderson, B.E., Albanes, D., Altshuler, D., Berglund, G., Berrino, F., Bingham, S, Buring, J.E., Burtt, N.P., Calle, E.E., Chanock, S.J., Clavel-Chapelon, F., Colditz, G., Diver, W.R., Freedman, M.L., Haiman, C.A., Hankinson, S.E., Hayes, R.B., Hirschhorn, J.N., Hunter, D., Kolonel, L.N., Kraft, P., LeMarchand, L., Linseisen, J., Modi, W., Navarro, C., Peeters, P.H.M., Pike, M.C., Riboli, E., Setiawan, V.W., Stram, D.O., Thomas, G., Thun, M.J., Tjonneland, A., and Trichopoulos, D.

Published
2006

26. Haplotype analysis of the HSD17B1 gene and risk of breast cancer: a comprehensive approach to multicenter analyses of prospective cohort studies.

Author

JC onderzoeksprogramma Kanker, Epidemiology & Health Economics, Feigelson, H.S., Cox, D.G., Cann, H.M., Wacholder, S., Kaaks, R., Henderson, B.E., Albanes, D., Altshuler, D., Berglund, G., Berrino, F., Bingham, S, Buring, J.E., Burtt, N.P., Calle, E.E., Chanock, S.J., Clavel-Chapelon, F., Colditz, G., Diver, W.R., Freedman, M.L., Haiman, C.A., Hankinson, S.E., Hayes, R.B., Hirschhorn, J.N., Hunter, D., Kolonel, L.N., Kraft, P., LeMarchand, L., Linseisen, J., Modi, W., Navarro, C., Peeters, P.H.M., Pike, M.C., Riboli, E., Setiawan, V.W., Stram, D.O., Thomas, G., Thun, M.J., Tjonneland, A., Trichopoulos, D., JC onderzoeksprogramma Kanker, Epidemiology & Health Economics, Feigelson, H.S., Cox, D.G., Cann, H.M., Wacholder, S., Kaaks, R., Henderson, B.E., Albanes, D., Altshuler, D., Berglund, G., Berrino, F., Bingham, S, Buring, J.E., Burtt, N.P., Calle, E.E., Chanock, S.J., Clavel-Chapelon, F., Colditz, G., Diver, W.R., Freedman, M.L., Haiman, C.A., Hankinson, S.E., Hayes, R.B., Hirschhorn, J.N., Hunter, D., Kolonel, L.N., Kraft, P., LeMarchand, L., Linseisen, J., Modi, W., Navarro, C., Peeters, P.H.M., Pike, M.C., Riboli, E., Setiawan, V.W., Stram, D.O., Thomas, G., Thun, M.J., Tjonneland, A., and Trichopoulos, D.

Published
2006

29. Loss of heterozygosity for chromosome 14q in neuroblastoma

Author

Thompson, P.M., primary, Seifried, B.A., additional, Kyemba, S.K., additional, Jensen, S.J., additional, Guo, C., additional, Maris, J.M., additional, Brodeur, G.M., additional, Stram, D.O., additional, Seeger, R.C., additional, Gerbing, R., additional, Matthay, K.K., additional, Matise, T.C., additional, and White, P.S., additional

Published
2001
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33. Bayesian Spatial Modeling of Haplotype Associations

Author

Thomas, D.C., Stram, D.O., Conti, D., Molitor, J., and Marjoram, P.

Abstract

AbstractWe review methods for relating the risk of disease to a collection of single nucleotide polymorphisms (SNPs) within a small region. Association studies using case-control designs with unrelated individuals could be used either to test for a direct effect of a candidate gene and characterize the responsible variant(s), or to fine map an unknown gene by exploiting the pattern of linkage disequilibrium (LD). We consider a flexible class of logistic penetrance models based on haplotypes and compare them with an alternative formulation based on unphased multilocus genotypes. The likelihood for haplotype-based models requires summation over all possible haplotype assignments consistent with the observed genotype data, and can be fitted using either Expectation-Maximization (E-M) or Markov chain Monte Carlo (MCMC) methods. Subtleties involving ascertainment correction for case-control studies are discussed. There has been great interest in methods for LD mapping based on the coalescent or ancestral recombination graphs as well as methods based on haplotype sharing, both of which we review briefly. Because of their computational complexity, we propose some alternative empirical modeling approaches using techniques borrowed from the Bayesian spatial statistics literature. Here, space is interpreted in terms of a distance metric describing the similarity of any pair of haplotypes to each other, and hence their presumed common ancestry. Specifically, we discuss the conditional autoregressive model and two spatial clustering models: Potts and Voronoi. We conclude with a discussion of the implications of these methods for modeling cryptic relatedness, haplotype blocks, and haplotype tagging SNPs, and suggest a Bayesian framework for the HapMap project.Copyright © 2003 S. Karger AG, Basel

Published
2003

34. Modeling and E-M Estimation of Haplotype-Specific Relative Risks from Genotype Data for a Case-Control Study of Unrelated Individuals

Author

Stram, D.O., Pearce, C. Leigh, Bretsky, P., Freedman, M., Hirschhorn, J.N., Altshuler, D., Kolonel, L.N., Henderson, B.E., and Thomas, D.C.

Abstract

AbstractThe US National Cancer Institute has recently sponsored the formation of a Cohort Consortium (http://2002.cancer.gov/scpgenes.htm) to facilitate the pooling of data on very large numbers of people, concerning the effects of genes and environment on cancer incidence. One likely goal of these efforts will be generate a large population-based case-control series for which a number of candidate genes will be investigated using SNP haplotype as well as genotype analysis. The goal of this paper is to outline the issues involved in choosing a method of estimating haplotype-specific risk estimates for such data that is technically appropriate and yet attractive to epidemiologists who are already comfortable with odds ratios and logistic regression. Our interest is to develop and evaluate extensions of methods, based on haplotype imputation, that have been recently described (Schaid et al., Am J Hum Genet, 2002, and Zaykin et al., Hum Hered, 2002) as providing score tests of the null hypothesis of no effect of SNP haplotypes upon risk, which may be used for more complex tasks, such as providing confidence intervals, and tests of equivalence of haplotype-specific risks in two or more separate populations. In order to do so we (1) develop a cohort approach towards odds ratio analysis by expanding the E-M algorithm to provide maximum likelihood estimates of haplotype-specific odds ratios as well as genotype frequencies; (2) show how to correct the cohort approach, to give essentially unbiased estimates for population-based or nested case-control studies by incorporating the probability of selection as a case or control into the likelihood, based on a simplified model of case and control selection, and (3) finally, in an example data set (CYP17 and breast cancer, from the Multiethnic Cohort Study) we compare likelihood-based confidence interval estimates from the two methods with each other, and with the use of the single-imputation approach of Zaykin et al. applied under both null and alternative hypotheses. We conclude that so long as haplotypes are well predicted by SNP genotypes (we use the R2h criteria of Stram et al. [1]) the differences between the three methods are very small and in particular that the single imputation method may be expected to work extremely well.Copyright © 2003 S. Karger AG, Basel

Published
2003

35. Viral load in heterosexual transmission of human immunodeficiency virus type 1 by blood transfusion recipients

Author

Operskalski, E.A., Stram, D.O., Busch, M.P., Huang, W., Harris, M., Dietrich, S.L., Schiff, E.R., Donegan, E., and Mosley, J.W.

Subjects
HIV infection, Blood transfusion -- Complications
Abstract

Transmission (HIV) Operskalski, E.A.; Stram, D.O.; Busch, M.P.; Huang, W.; Harris, M.; Dietrich, S.L.; Schiff, E.R.; Donegan, E.; Mosley, J.W. "Role of Viral Load in Heterosexual Transmission of Human Immunodeficiency [...]

Published
1997

36. Factors influencing human immunodeficiency virus type 1 transmission by blood transfusion

Author

Busch, M.P., Operskalski, E.A., Mosley, J.W., Lee, T.H., Henrard, D., Herman, S., Sachs, D.H., Harris, M., Huang, W., and Stram, D.O.

Subjects
HIV infection, Blood transfusion -- Complications
Abstract

According to the authors' abstract of an article published in Journal of Infectious Diseases, "One hundred thirty-two recipients of blood components that retrospectively tested positive for antibody to human immunodeficiency [...]

Published
1996

37. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

Author

Hidemi Ito, Stephen K. Van Den Eeden, Abdisamad M. Ibrahim, Ching C. Lau, Preetha Rajaraman, Gloria M. Petersen, Judith Hoffman-Bolton, Colin P.N. Dinney, Chang Hyun Kang, Melinda C. Aldrich, Mark P. Purdue, Xiao-Ou Shu, William J. Blot, Sanjay Shete, Alpa V. Patel, Charles Kooperberg, Paolo Vineis, David Van Den Berg, Chao A. Hsiung, Anthony J. Swerdlow, Qing Lan, Wu Chou Su, Afshan Siddiq, Ulrike Peters, Katia Scotlandi, Sara H. Olson, Kendra Schwartz, Kelly L. Bolton, Chancellor Hohensee, Josep Lloreta, Kevin B. Jacobs, Debra T. Silverman, Rudolf Kaaks, Wei Zheng, Steven Gallinger, Junwen Wang, Angela Carta, Massimo Serra, Petra H.M. Peeters, Victoria L. Stevens, Yasushi Yatabe, Geraldine Cancel-Tassin, Joshua N. Sampson, Young Tae Kim, Graham A. Colditz, Pan-Chyr Yang, Baosen Zhou, Fredrick R. Schumacher, Nicolas Wentzensen, Evelyn Tay, Claudia Maria Hattinger, Chen Wu, Pilar Amiano, Mattias Johansson, Maxwell P. Lee, Christian P. Kratz, Michael B. Cook, Mingfeng Zhang, Kay-Tee Khaw, Jian-Min Yuan, Anne Zeleniuch-Jacquotte, Jinping Jia, Roberto Tirabosco, Jing Ma, Neil E. Caporaso, Christopher A. Haiman, Bu Tian Ji, Adrienne M. Flanagan, Neyssa Marina, Eric J. Jacobs, Sophia S. Wang, Chong-Jen Yu, Edward Giovannucci, Margaret Wrensch, Robert L. Grubb, Bin Zhu, Daniel O. Stram, Manolis Kogevinas, Margaret R. Karagas, Mazda Jenab, Alison M. Mondul, Jun Xu, Preethi S. Raj, Anders Ahlbom, Christine D. Berg, Shelley Niwa, Kala Visvanathan, Loic Le Marchand, Jorge R. Toro, Robert N. Hoover, Heather Spencer Feigelson, Michelle Brotzman, Laurence N. Kolonel, Krista A. Zanetti, Chengfeng Wang, Mary Ann Butler, Ann Truelove, Irene L. Andrulis, Hongbing Shen, H. Dean Hosgood, Ming Shyan Huang, Gee-Chen Chang, Jianjun Liu, John K. Wiencke, Stephanie J. Weinstein, Beatrice Melin, Kouya Shiraishi, Zhihua Yin, Lee E. Moore, Börje Ljungberg, Jolanta Lissowska, Elizabeth M. Gillanders, M. T. Landi, Cari M. Kitahara, Maria Feychting, Kuan-Yu Chen, Matthias Simon, Brian M. Wolpin, Hemang Parikh, Hannah P. Yang, Graham G. Giles, Alison Johnson, Demetrius Albanes, Carlos González, Brian E. Henderson, Xifeng Wu, Harvey A. Risch, Amy Hutchinson, Christopher Hautman, Constance Chen, Zhibin Hu, Donghui Li, Elio Riboli, Julie E. Buring, Curtis C. Harris, Xu Che, Núria Malats, Roger Henriksson, Rosario Tumino, Joanne S. Colt, Alfredo Carrato, Paolo Boffetta, Maria Pik Wong, Hideo Tanaka, Federico Canzian, Alan D. L. Sihoe, Chien-Jen Chen, Kenneth Muir, Chen Ying, Qincheng He, Melissa C. Southey, Marc Sanson, Victoria K. Cortessis, Sharon A. Savage, Wei Hu, Yao Tettey, Daniela S. Gerhard, Sofia Pavanello, Guangwen Cao, H. Barton Grossman, Michael Goggins, Hideo Kunitoh, Peter D. Inskip, Seth P. Lerner, Peter Kraft, David Thomas, Peng Guan, Chung Hsing Chen, I. Shou Chang, Christoffer Johansen, Roberta McKean-Cowdin, Lee J. Helman, Yuh Min Chen, Ana Patiño-García, Pär Stattin, Xiaoping Miao, Tangchun Wu, Jay S. Wunder, Ann W. Hsing, Yu-Tang Gao, Brooke L. Fridley, Tania Carreón, Charles C. Chung, Nan Hu, Yoo Jin Jung, Richard B. Biritwum, Eric J. Duell, Philip R. Taylor, Satu Männistö, Kai Yu, Meredith Yeager, Xia Pu, Vittorio Krogh, Anand P. Chokkalingam, Susan M. Gapstur, W. Ryan Diver, Yuanqing Ye, Keitaro Matsuo, Cecilia Arici, You-Lin Qiao, Alan R. Schned, Dominique S. Michaud, Joanne W. Elena, Christopher Kim, Dongxin Lin, Yun-Chul Hong, Daru Lu, Reina García-Closas, Jonine D. Figueroa, Linda M. Liao, Yi-Long Wu, Heiner Boeing, Mark Lathrop, Göran Hallmans, Elizabeth A. Holly, Carol Giffen, Andrew A. Adjei, Consol Serra, Anne Tjønneland, Joseph F. Fraumeni, Alisa M. Goldstein, Ruth C. Travis, Rebecca Troisi, Dalsu Baris, Nalan Gokgoz, Olivier Cussenot, Xiang Deng, Yeul Hong Kim, Malin Sund, Sonja I. Berndt, E. David Crawford, Edward D. Yeboah, Sook Whan Sung, Françoise Clavel-Chapelon, Woon-Puay Koh, Nilgun Kurucu, Richard B. Hayes, Ashish M. Kamat, Beata Peplonska, Laurie Burdette, Ze Zhang Tang, Alan A. Arslan, Malcolm C. Pike, Sabina Sierri, J. Michael Gaziano, Lorna H. McNeil, Katherine A. McGlynn, Ulla Vogel, Logan G. Spector, H. Bas Bueno-de-Mesquita, Stephen J. Chanock, Jae Yong Park, Jennifer Prescott, Fernando Lecanda, Margaret A. Tucker, Ti Ding, Christian C. Abnet, Jenny Chang-Claude, Dimitrios Trichopoulos, Wei-Yen Lim, Wen Tan, Nick Orr, Jin Hee Kim, Stefano Porru, Chand Khanna, Robert R. McWilliams, Zhaoming Wang, Jeong Seon Ryu, David V. Conti, Alison P. Klein, Adonina Tardón, Robert J. Klein, Rebecca J. Rodabough, Mark H. Greene, Aruna Kamineni, Jie Lin, Rachael Z. Stolzenberg-Solomon, Patricia Hartge, Susan E. Hankinson, Young-Chul Kim, In Sam Kim, Luis Sierrasesúmaga, Roel Vermeulen, Paige M. Bracci, Mariana C. Stern, Louise A. Brinton, Myron D. Gross, Yong-Bing Xiang, Chih Yi Chen, G. A. Gerald Andriole, Paul S. Meltzer, Ying-Huang Tsai, Faith G. Davis, Ulrika Andersson, Paul Brennan, Sara Lindström, Chaoyu Wang, Giuseppe Mastrangelo, Laufey T. Amundadottir, Immaculata De Vivo, Bryan A. Bassig, Elisabete Weiderpass, Takashi Kohno, Nilanjan Chatterjee, Margaret R. Spitz, Pier Alberto Bertazzi, William Wheeler, David J. Hunter, Wei Tang, Qiuyin Cai, Naomi E. Allen, Molly Schwenn, Emily White, Min Shen, Adeline Seow, Laura E. Beane Freeman, James E. Mensah, Howard D. Sesso, Anna Luisa Di Stefano, Amanda Black, Manuela Gago-Dominguez, Christine B. Ambrosone, Avima M. Ruder, Martha S. Linet, Meir J. Stampfer, Robert C. Kurtz, Donald A. Barkauskas, Lisa W. Chu, Montserrat Garcia-Closas, Jason W. Hoskins, Melissa A. Austin, Kyoung Mu Lee, Jianxin Shi, Charles S. Fuchs, Nathaniel Rothman, Richard Gorlick, Piero Picci, Gianluca Severi, Ann G. Schwartz, Jian Gu, Christopher I. Amos, Marie-Christine Boutron-Ruault, Salvatore Panico, Alicja Wolk, Sara S. Strom, Lisa Mirabello, Jin-Hu Fan, Chin-Fu Hsiao, Neal D. Freedman, Geoffrey S. Tobias, Julie M. Gastier-Foster, Wang, Z, Zhu, B, Zhang, M, Parikh, H, Jia, J, Chung, Cc, Sampson, Jn, Hoskins, Jw, Hutchinson, A, Burdette, L, Ibrahim, A, Hautman, C, Raj, P, Abnet, Cc, Adjei, Aa, Ahlbom, A, Albanes, D, Allen, Ne, Ambrosone, Cb, Aldrich, M, Amiano, P, Amos, C, Andersson, U, Andriole G., Jr, Andrulis, Il, Arici, C, Arslan, Aa, Austin, Ma, Baris, D, Barkauskas, Da, Bassig, Ba, Beane Freeman, Le, Berg, Cd, Berndt, Si, Bertazzi, Pa, Biritwum, Rb, Black, A, Blot, W, Boeing, H, Boffetta, P, Bolton, K, Boutron Ruault, Mc, Bracci, Pm, Brennan, P, Brinton, La, Brotzman, M, Bueno de Mesquita, Hb, Buring, Je, Butler, Ma, Cai, Q, Cancel Tassin, G, Canzian, F, Cao, G, Caporaso, Ne, Carrato, A, Carreon, T, Carta, A, Chang, Gc, Chang, I, Chang Claude, J, Che, X, Chen, Cj, Chen, Cy, Chen, Ch, Chen, C, Chen, Ky, Chen, Ym, Chokkalingam, Ap, Chu, Lw, Clavel Chapelon, F, Colditz, Ga, Colt, J, Conti, D, Cook, Mb, Cortessis, Vk, Crawford, Ed, Cussenot, O, Davis, Fg, De Vivo, I, Deng, X, Ding, T, Dinney, Cp, Di Stefano, Al, Diver, Wr, Duell, Ej, Elena, Jw, Fan, Jh, Feigelson, H, Feychting, M, Figueroa, Jd, Flanagan, Am, Fraumeni JF, Jr, Freedman, Nd, Fridley, Bl, Fuchs, C, Gago Dominguez, M, Gallinger, S, Gao, Yt, Gapstur, Sm, Garcia Closas, M, Garcia Closas, R, Gastier Foster, Jm, Gaziano, Jm, Gerhard, D, Giffen, Ca, Giles, Gg, Gillanders, Em, Giovannucci, El, Goggins, M, Gokgoz, N, Goldstein, Am, Gonzalez, C, Gorlick, R, Greene, Mh, Gross, M, Grossman, Hb, Grubb R., 3rd, Gu, J, Guan, P, Haiman, Ca, Hallmans, G, Hankinson, Se, Harris, Cc, Hartge, P, Hattinger, C, Hayes, Rb, He, Q, Helman, L, Henderson, Be, Henriksson, R, Hoffman Bolton, J, Hohensee, C, Holly, Ea, Hong, Yc, Hoover, Rn, Hosgood HD, 3rd, Hsiao, Cf, Hsing, Aw, Hsiung, Ca, Hu, N, Hu, W, Hu, Z, Huang, M, Hunter, Dj, Inskip, Pd, Ito, H, Jacobs, Ej, Jacobs, Kb, Jenab, M, Ji, Bt, Johansen, C, Johansson, M, Johnson, A, Kaaks, R, Kamat, Am, Kamineni, A, Karagas, M, Khanna, C, Khaw, Kt, Kim, C, Kim, I, Kim, Yh, Kim, Yc, Kim, Yt, Kang, Ch, Jung, Yj, Kitahara, Cm, Klein, Ap, Klein, R, Kogevinas, M, Koh, Wp, Kohno, T, Kolonel, Ln, Kooperberg, C, Kratz, Cp, Krogh, V, Kunitoh, H, Kurtz, Rc, Kurucu, N, Lan, Q, Lathrop, M, Lau, Cc, Lecanda, F, Lee, Km, Lee, Mp, Le Marchand, L, Lerner, Sp, Li, D, Liao, Lm, Lim, Wy, Lin, D, Lin, J, Lindstrom, S, Linet, M, Lissowska, J, Liu, J, Ljungberg, B, Lloreta, J, Lu, D, Ma, J, Malats, N, Mannisto, S, Marina, N, Mastrangelo, G, Matsuo, K, Mcglynn, Ka, McKean Cowdin, R, Mcneill, Lh, Mcwilliams, Rr, Melin, B, Meltzer, P, Mensah, Je, Miao, X, Michaud, D, Mondul, Am, Moore, Le, Muir, K, Niwa, S, Olson, Sh, Orr, N, Panico, Salvatore, Park, Jy, Patel, Av, Patino Garcia, A, Pavanello, S, Peeters, Ph, Peplonska, B, Peters, U, Petersen, Gm, Picci, P, Pike, Mc, Porru, S, Prescott, J, Pu, X, Purdue, Mp, Qiao, Yl, Rajaraman, P, Riboli, E, Risch, Ha, Rodabough, Rj, Rothman, N, Ruder, Am, Ryu, J, Sanson, M, Schned, A, Schumacher, Fr, Schwartz, Ag, Schwartz, Kl, Schwenn, M, Scotlandi, K, Seow, A, Serra, C, Serra, M, Sesso, Hd, Severi, G, Shen, H, Shen, M, Shete, S, Shiraishi, K, Shu, Xo, Siddiq, A, Sierrasesumaga, L, Sierri, S, Loon Sihoe, Ad, Silverman, Dt, Simon, M, Southey, Mc, Spector, L, Spitz, M, Stampfer, M, Stattin, P, Stern, Mc, Stevens, Vl, Stolzenberg Solomon, Rz, Stram, Do, Strom, S, Su, Wc, Sund, M, Sung, Sw, Swerdlow, A, Tan, W, Tanaka, H, Tang, W, Tang, Zz, Tardon, A, Tay, E, Taylor, Pr, Tettey, Y, Thomas, Dm, Tirabosco, R, Tjonneland, A, Tobias, G, Toro, Jr, Travis, Rc, Trichopoulos, D, Troisi, R, Truelove, A, Tsai, Yh, Tucker, Ma, Tumino, R, Van Den Berg, D, Van Den Eeden, Sk, Vermeulen, R, Vineis, P, Visvanathan, K, Vogel, U, Wang, C, Wang, J, Wang, S, Weiderpass, E, Weinstein, Sj, Wentzensen, N, Wheeler, W, White, E, Wiencke, Jk, Wolk, A, Wolpin, Bm, Wong, Mp, Wrensch, M, Wu, C, Wu, T, Wu, X, Wu, Yl, Wunder, J, Xiang, Yb, Xu, J, Yang, Hp, Yang, Pc, Yatabe, Y, Ye, Y, Yeboah, Ed, Yin, Z, Ying, C, Yu, Cj, Yu, K, Yuan, Jm, Zanetti, Ka, Zeleniuch Jacquotte, A, Zheng, W, Zhou, B, Mirabello, L, Savage, Sa, Kraft, P, Chanock, Sj, Yeager, M, Landi, Mt, Shi, J, Chatterjee, N, Amundadottir, Lt, Wang, Z., Zhu, B., Zhang, M., Parikh, H., Jia, J., Chung, C.C., Sampson, J.N., Hoskins, J.W., Hutchinson, A., Burdette, L., Ibrahim, A., Hautman, C., Raj, P.S., Abnet, C.C., Adjei, A.A., Ahlbom, A., Albanes, D., Allen, N.E., Ambrosone, C.B., Aldrich, M., Amiano, P., Amos, C., Andersson, U., Gerald Andriole, G.A., Jr., Andrulis, I.L., Arici, C., Arslan, A.A., Austin, M.A., Baris, D., Barkauskas, D.A., Bassig, B.A., Freeman, L.E.B., Berg, C.D., Berndt, S.I., Bertazzi, P.A., Biritwum, R.B., Black, A., Blot, W., Boeing, H., Boffetta, P., Bolton, K., Boutron-Ruault, M.-C., Bracci, P.M., Brennan, P., Brinton, L.A., Brotzman, M., Bueno-de-Mesquita, H.B., Buring, J.E., Butler, M.A., Cai, Q., Cancel-Tassin, G., Canzian, F., Cao, G., Caporaso, N.E., Carrato, A., Carreon, T., Carta, A., Chang, G.-C., Chang, I.-S., Chang-Claude, J., Che, X., Chen, C.-J., Chen, C.-Y., Chen, C.-H., Chen, C., Chen, K.-Y., Chen, Y.-M., Chokkalingam, A.P., Chu, L.W., Clavel-Chapelon, F., Colditz, G.A., Colt, J.S., Conti, D., Cook, M.B., Cortessis, V.K., Crawford, E.D., Cussenot, O., Davis, F.G., De Vivo, I., Deng, X., Ding, T., Dinney, C.P., Di Stefano, A.L., Diver, W.R., Duell, E.J., Elena, J.W., Fan, J.-H., Feigelson, H.S., Feychting, M., Figueroa, J.D., Flanagan, A.M., Fraumeni, J.F., Jr., Freedman, N.D., Fridley, B.L., Fuchs, C.S., Gago-Dominguez, M., Gallinger, S., Gao, Y.-T., Gapstur, S.M., Garcia-Closas, M., Garcia-Closas, R., Gastier-Foster, J.M., Gaziano, J.M., Gerhard, D.S., Giffen, C.A., Giles, G.G., Gillanders, E.M., Giovannucci, E.L., Goggins, M., Gokgoz, N., Goldstein, A.M., Gonzalez, C., Gorlick, R., Greene, M.H., Gross, M., Grossman, H.B., Grubb, R., III and Gu, J., Guan, P., Haiman, C.A., Hallmans, G., Hankinson, S.E., Harris, C.C., Hartge, P., Hattinger, C., Hayes, R.B., He, Q., Helman, L., Henderson, B.E., Henriksson, R., Hoffman-Bolton, J., Hohensee, C., Holly, E.A., Hong, Y.-C., Hoover, R.N., Dean Hosgood, H., Hsiao, C.-F., Hsing, A.W., Hsiung, C.A., Hu, N., Hu, W., Hu, Z., Huang, M.-S., Hunter, D.J., Inskip, P.D., Ito, H., Jacobs, E.J., Jacobs, K.B., Jenab, M., Ji, B.-T., Johansen, C., Johansson, M., Johnson, A., Kaaks, R., Kamat, A.M., Kamineni, A., Karagas, M., Khanna, C., Khaw, K.-T., Kim, C., Kim, I.-S., Kim, J.H., Kim, Y.H., Kim, Y.-C., Kim, Y.T., Kang, C.H., Jung, Y.J., Kitahara, C.M., Klein, A.P., Klein, R., Kogevinas, M., Koh, W.-P., Kohno, T., Kolonel, L.N., Kooperberg, C., Kratz, C.P., Krogh, V., Kunitoh, H., Kurtz, R.C., Kurucu, N., Lan, Q., Lathrop, M., Lau, C.C., Lecanda, F., Lee, K.-M., Lee, M.P., Marchand, L.L., Lerner, S.P., Li, D., Liao, L.M., Lim, W.-Y., Lin, D., Lin, J., Lindstrom, S., Linet, M.S., Lissowska, J., Liu, J., Ljungberg, B., Lloreta, J., Lu, D., Ma, J., Malats, N., Mannisto, S., Marina, N., Mastrangelo, G., Matsuo, K., McGlynn, K.A., McKean-Cowdin, R., McNeil, L.H., McWilliams, R.R., Melin, B.S., Meltzer, P.S., Mensah, J.E., Miao, X., Michaud, D.S., Mondul, A.M., Moore, L.E., Muir, K., Niwa, S., Olson, S.H., Orr, N., Panico, S., Park, J.Y., Patel, A.V., Patino-Garcia, A., Pavanello, S., Peeters, P.H.M., Peplonska, B., Peters, U., Petersen, G.M., Picci, P., Pike, M.C., Porru, S., Prescott, J., Pu, X., Purdue, M.P., Qiao, Y.-L., Rajaraman, P., Riboli, E., Risch, H.A., Rodabough, R.J., Rothman, N., Ruder, A.M., Ryu, J.-S., Sanson, M., Schned, A., Schumacher, F.R., Schwartz, A.G., Schwartz, K.L., Schwenn, M., Scotlandi, K., Seow, A., Serra, C., Serra, M., Sesso, H.D., Severi, G., Shen, H., Shen, M., Shete, S., Shiraishi, K., Shu, X.-O., Siddiq, A., Sierrasesumaga, L., Sierri, S., Sihoe, A.D.L., Silverman, D.T., Simon, M., Southey, M.C., Spector, L., Spitz, M., Stampfer, M., Stattin, P., Stern, M.C., Stevens, V.L., Stolzenberg-Solomon, R.Z., Stram, D.O., Strom, S.S., Su, W.-C., Sund, M., Sung, S.W., Swerdlow, A., Tan, W., Tanaka, H., Tang, W., Tang, Z.-Z., Tardon, A., Tay, E., Taylor, P.R., Tettey, Y., Thomas, D.M., Tirabosco, R., Tjonneland, A., Tobias, G.S., Toro, J.R., Travis, R.C., Trichopoulos, D., Troisi, R., Truelove, A., Tsai, Y.-H., Tucker, M.A., Tumino, R., Van Den Berg, D., Van Den Eeden, S.K., Vermeulen, R., Vineis, P., Visvanathan, K., Vogel, U., Wang, C., Wang, J., Wang, S.S., Weiderpass, E., Weinstein, S.J., Wentzensen, N., Wheeler, W., White, E., Wiencke, J.K., Wolk, A., Wolpin, B.M., Wong, M.P., Wrensch, M., Wu, C., Wu, T., Wu, X., Wu, Y.-L., Wunder, J.S., Xiang, Y.-B., Xu, J., Yang, H.P., Yang, P.-C., Yatabe, Y., Ye, Y., Yeboah, E.D., Yin, Z., Ying, C., Yu, C.-J., Yu, K., Yuan, J.-M., Zanetti, K.A., Zeleniuch-Jacquotte, A., Zheng, W., Zhou, B., Mirabello, L., Savage, S.A., Kraft, P., Chanock, S.J., Yeager, M., Landi, M.T., Shi, J., Chatterjee, N., and Amundadottir, L.T.

Subjects
Male, SINGLE-NUCLEOTIDE POLYMORPHISM, Genome-wide association study, Epigenesis, Genetic, Gene Frequency, Molecular Biology, Genetics, Genetics (clinical), Neoplasms, Odds Ratio, Genome-wide association studies (GWAS), Telomerase, DNA METHYLATION Author Information, Association Studies Articles, General Medicine, PANCREATIC-CANCER, PROSTATE-CANCER, Neoplasm Proteins, POSTMENOPAUSAL BREAST-CANCER, TERT PROMOTER MUTATIONS, Gene Expression Regulation, Neoplastic, 2 SUSCEPTIBILITY LOCI, DNA methylation, Chromosomes, Human, Pair 5, Female, Risk, Locus (genetics), Single-nucleotide polymorphism, TERT and CLPTM1L gene, Biology, Polymorphism, Single Nucleotide, LUNG-CANCER, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Allele, Gene, Allele frequency, Alleles, Genetic association, chromosome 5p15.33, Computational Biology, Membrane Proteins, DNA Methylation, Genetic Loci, TELOMERE LENGTH, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 x 10(-39); Region 3: rs2853677, P = 3.30 x 10(-36) and PConditional = 2.36 x 10(-8); Region 4: rs2736098, P = 3.87 x 10(-12) and PConditional = 5.19 x 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 x 10(-6); and Region 6: rs10069690, P = 7.49 x 10(-15) and PConditional = 5.35 x 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 x 10(-18) and PConditional = 7.06 x 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

Published
2014

38. Gene-environment interactions in cancer epidemiology: A national cancer institute think tank report

Author

Hutter, C. M., Mechanic, L. E., Chatterjee, N., Kraft, P., Gillanders, E. M., Abnet, C. C., Amos, C., Balshaw, D., Bickeböller, H., Bierut, L. J., Boffetta, P., Bondy, M., Chanock, S., Chen, H. -S., Cox, N., Vivo, I. D., Divi, R., Dupuis, J., Ellison, G., Fallin, M. D., Gauderman, W. J., Gillanders, E., Haiman, C., Hutter, C., Simonds, N. I., Iversen, E., Khoury, M. J., Marchand, L. L., McAllister, K., Mechanic, L., Peters, U., Prentice, R., Rebbeck, T., Reedy, J., Rothman, N., Schully, S., Seminara, D., Shaughnessy, D., Shete, S., Spiegelman, D., Stram, D. O., BALDWIN, THOMAS DONALD, Wang, M., WANG, WENPING, WEINBERG, CAREN HELENE, Winn, D. M., Witte, J. S., Hutter, C.M., Mechanic, L.E., Chatterjee, N., Kraft, P., Gillanders, E.M., Abnet, C.C., Amos, C., Balshaw, D., Bickeböller, H., Bierut, L.J., Boffetta, P., Bondy, M., Chanock, S., Chen, H.-S., Cox, N., Vivo, I.D., Divi, R., Dupuis, J., Ellison, G., Fallin, M.D., Gauderman, W.J., Gillanders, E., Haiman, C., Hutter, C., Simonds, N.I., Iversen, E., Khoury, M.J., Marchand, L.L., McAllister, K., Mechanic, L., Peters, U., Prentice, R., Rebbeck, T., Reedy, J., Rothman, N., Schully, S., Seminara, D., Shaughnessy, D., Shete, S., Spiegelman, D., Stram, D.O., Thomas, D., Wang, M., Wang, W., Weinberg, C., Winn, D.M., and Witte, J.S.

Subjects
Gene-environment interactions, complex phenotypes, genetic epidemiology
Abstract

Cancer risk is determined by a complex interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified hundreds of common (minor allele frequency [MAF] > 0.05) and less common (0.01 < MAF < 0.05) genetic variants associated with cancer. The marginal effects of most of these variants have been small (odds ratios: 1.1-1.4). There remain unanswered questions on how best to incorporate the joint effects of genes and environment, including gene-environment (G × E) interactions, into epidemiologic studies of cancer. To help address these questions, and to better inform research priorities and allocation of resources, the National Cancer Institute sponsored a "Gene-Environment Think Tank" on January 10-11, 2012. The objective of the Think Tank was to facilitate discussions on (1) the state of the science, (2) the goals of G × E interaction studies in cancer epidemiology, and (3) opportunities for developing novel study designs and analysis tools. This report summarizes the Think Tank discussion, with a focus on contemporary approaches to the analysis of G × E interactions. Selecting the appropriate methods requires first identifying the relevant scientific question and rationale, with an important distinction made between analyses aiming to characterize the joint effects of putative or established genetic and environmental factors and analyses aiming to discover novel risk factors or novel interaction effects. Other discussion items include measurement error, statistical power, significance, and replication. Additional designs, exposure assessments, and analytical approaches need to be considered as we move from the current small number of success stories to a fuller understanding of the interplay of genetic and environmental factors. © 2013 WILEY PERIODICALS, INC.

Published
2013

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