73 results on '"Koppova, K"'
Search Results
2. Case–control study in basal cell carcinoma of the skin: single nucleotide polymorphisms in three interleukin promoters pre-analysed in pooled DNA
- Author
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Wilkening, S., Hemminki, K., Rudnai, P., Gurzau, E., Koppova, K., Kumar, R., and Försti, A.
- Published
- 2006
3. Genome-wide association study identifies multiple risk loci for renal cell carcinoma
- Author
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Scelo, G, Purdue, MP, Brown, KM, Johansson, M, Wang, Z, Eckel-Passow, JE, Ye, Y, Hoffman, JN, Choi, J, Foll, M, Gaborieau, V, Machiela, MJ, Colli, LM, Li, P, Sampson, JN, Abedi-Ardekani, B, Besse, C, Blanche, H, Boland, A, Burdette, L, Charbrier, A, Durand, G, Le Calvez-Kelm, F, Prokhortchouk, E, Robinot, N, Skyrabin, KG, Wozniak, MB, Yeager, M, Basta-Jovanovich, G, Dzamic, Z, Foretova, L, Holcatova, I, Janout, V, Mates, D, Mukeriya, A, Rascu, S, Zaridze, D, Bencko, V, Cybulski, C, Fabianova, E, Jinga, V, Lissowska, J, Lubinski, J, Navratilova, M, Rudnai, P, Szeszenia-Dabrowska, N, Benhamou, S, Cancel-Tassin, G, Cussenot, O, Baglietto, L, Boeing, H, Khaw, K-T, Weiderpass, E, Ljungberg, B, Sitaram, RT, Bruinsma, F, Jordan, SJ, Severi, G, Winship, I, Hveem, K, Vatten, LJ, Fletcher, T, Koppova, K, Larsson, SC, Wolk, A, Banks, RE, Selby, PJ, Easton, DF, Pharoah, P, Andreotti, G, Beane Freeman, LE, Koutros, S, Albanes, D, Mannisto, S, Weinstein, S, Clark, PE, Edwards, TL, Lipworth, L, Gapstur, SM, Stevens, VL, Carol, H, Freedman, ML, Pomerantz, MM, Cho, E, Kraft, P, Preston, MA, Wilson, KM, Gaziano, JM, Sesso, HD, Black, A, Freedman, ND, Huang, WY, Anema, JG, Kahnoski, RJ, Lane, BR, Noyes, SL, Petillo, D, Teh, BT, Peters, U, White, E, Anderson, GL, Johnson, L, Luo, J, Buring, J, Lee, I-M, Chow, W-H, Moore, LE, Wood, C, Eisen, T, Henrion, M, Larkin, J, Barman, P, Leibovich, BC, Choueiri, TK, Lathrop, GM, Rothman, N, Deleuze, J-F, McKay, JD, Parker, AS, Wu, X, Houlston, RS, Brennan, P, and Chanock, SJ
- Abstract
Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10−10), 3p22.1 (rs67311347, P=2.5 × 10−8), 3q26.2 (rs10936602, P=8.8 × 10−9), 8p21.3 (rs2241261, P=5.8 × 10−9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10−8), 11q22.3 (rs74911261, P=2.1 × 10−10) and 14q24.2 (rs4903064, P=2.2 × 10−24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.
- Published
- 2017
4. Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP
- Author
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Cheng, T. H. T., Gorman, M., Martin, L., Barclay, E., Casey, G., Newcomb, P. A., Conti, D. V., Schumacher, F. R., Gallinger, S., Lindor, N. M., Hopper, J., Jenkins, M., Hunter, D. J., Kraft, P., Jacobs, K. B., Cox, D. G., Yeager, M., Hankinson, S. E., Wacholder, S., Wang, Z., Welch, R., Hutchinson, A., Wang, J., Yu, K., Chatterjee, N., Orr, N., Willett, W. C., Colditz, G. A., Ziegler, R. G., Berg, C. D., Buys, S. S., McCarty, C. A., Feigelson, H. S., Calle, E. E., Thun, M. J., Hayes, R. B., Tucker, M., Gerhard, D. S., Fraumeni, J. F., Jr., Hoover, R. N., Thomas, G., Chanock, S. J., Ciampa, J., Gonzalez-Bosquet, J., Berndt, S., Amundadottir, L., Diver, W. R., Albanes, D., Virtamo, J., Weinstein, S. J., Cancel-Tassin, G., Cussenot, O., Valeri, A., Andriole, G. L., Crawford, E. D., Haiman, C. A., Henderson, B., Kolonel, L., March, L. L., Siddiq, A., Riboli, E., Key, T. J., Kaaks, R., Isaacs, W., Isaacs, S., Wiley, K. E., Gronberg, H., Wiklund, F., Stattin, P., Xu, J., Zheng, S. L., Sun, J., Vatten, L. J., Hveem, K., Kumle, M., Purdue, M. P., Johansson, M., Zelenika, D., Toro, J. R., Scelo, G., Moore, L. E., Prokhortchouk, E., Wu, X., Kiemeney, L. A., Gaborieau, V., Chow, W. -H., Zaridze, D., Matveev, V., Lubinski, J., Trubicka, J., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Bucur, A., Bencko, V., Foretova, L., Janout, V., Boffetta, P., Colt, J. S., Davis, F. G., Schwartz, K. L., Banks, R. E., Selby, P. J., Harnden, P., Hsing, A. W., Grubb, R. L., III, Boeing, H., Vineis, P., Clavel-Chapelon, F., Palli, D., Tumino, R., Krogh, V., Panico, S., Duell, E. J., Quirós, J. R., Sanchez, M. -J., Navarro, C., Ardanaz, E., Dorronsoro, M., Khaw, K. -T., Allen, N. E., Bueno-de-Mesquita, H. B., Peeters, P. H. M., Trichopoulos, D., Linseisen, J., Ljungberg, B., Overvad, K., Tjønnel, Romieu, I., Mukeria, A., Shangina, O., Stevens, V. L., Gapstur, S. M., Pharoah, P. D., Easton, D. F., Njølstad, I., Tell, G. S., Stoltenberg, C., Kumar, R., Koppova, K., Benhamou, S., Oosterwijk, E., Vermeulen, S. H., Aben, K. K. H., Van Der Marel, S. L., Ye, Y., Wood, C. G., Pu, X., Mazur, A. M., Boulygina, E. S., Chekanov, N. N., Foglio, M., Lechner, D., Gut, I., Heath, S., Blanche, H., Skryabin, K. G., McKay, J. D., Rothman, N., Lathrop, M., Brennan, P., Saunders, B., Thomas, H., Clark, S., Tomlinson, I., and Cheng, T.H.T. and Gorman, M. and Martin, L. and Barclay, E. and Casey, G. and Newcomb, P.A. and Conti, D.V. and Schumacher, F.R. and Gallinger, S. and Lindor, N.M. and Hopper, J. and Jenkins, M. and Hunter, D.J. and Kraft, P. and Jacobs, K.B. and Cox, D.G. and Yeager, M. and Hankinson, S.E. and Wacholder, S. and Wang, Z. and Welch, R. and Hutchinson, A. and Wang, J. and Yu, K. and Chatterjee, N. and Orr, N. and Willett, W.C. and Colditz, G.A. and Ziegler, R.G. and Berg, C.D. and Buys, S.S. and McCarty, C.A. and Feigelson, H.S. and Calle, E.E. and Thun, M.J. and Hayes, R.B. and Tucker, M. and Gerhard, D.S. and Fraumeni, J.F., Jr. and Hoover, R.N. and Thomas, G. and Chanock, S.J. and Ciampa, J. and Gonzalez-Bosquet, J. and Berndt, S. and Amundadottir, L. and Diver, W.R. and Albanes, D. and Virtamo, J. and Weinstein, S.J. and Cancel-Tassin, G. and Cussenot, O. and Valeri, A. and Andriole, G.L. and Crawford, E.D. and Haiman, C.A. and Henderson, B. and Kolonel, L. and Marchand, L.L. and Siddiq, A. and Riboli, E. and Key, T.J. and Kaaks, R. and Isaacs, W. and Isaacs, S. and Wiley, K.E. and Gronberg, H. and Wiklund, F. and Stattin, P. and Xu, J. and Zheng, S.L. and Sun, J. and Vatten, L.J. and Hveem, K. and Kumle, M. and Purdue, M.P. and Johansson, M. and Zelenika, D. and Toro, J.R. and Scelo, G. and Moore, L.E. and Prokhortchouk, E. and Wu, X. and Kiemeney, L.A. and Gaborieau, V. and Chow, W.-H. and Zaridze, D. and Matveev, V. and Lubinski, J. and Trubicka, J. and Szeszenia-Dabrowska, N. and Lissowska, J. and Rudnai, P. and Fabianova, E. and Bucur, A. and Bencko, V. and Foretova, L. and Janout, V. and Boffetta, P. and Colt, J.S. and Davis, F.G. and Schwartz, K.L. and Banks, R.E. and Selby, P.J. and Harnden, P. and Hsing, A.W. and Grubb, R.L., III and Boeing, H. and Vineis, P. and Clavel-Chapelon, F. and Palli, D. and Tumino, R. and Krogh, V. and Panico, S. and Duell, E.J. and Quirós, J.R. and Sanchez, M.-J. and Navarro, C. and Ardanaz, E. and Dorronsoro, M. and Khaw, K.-T. and Allen, N.E. and Bueno-de-Mesquita, H.B. and Peeters, P.H.M. and Trichopoulos, D. and Linseisen, J. and Ljungberg, B. and Overvad, K. and Tjønneland, A. and Romieu, I. and Mukeria, A. and Shangina, O. and Stevens, V.L. and Gapstur, S.M. and Pharoah, P.D. and Easton, D.F. and Njølstad, I. and Tell, G.S. and Stoltenberg, C. and Kumar, R. and Koppova, K. and Benhamou, S. and Oosterwijk, E. and Vermeulen, S.H. and Aben, K.K.H. and Van Der Marel, S.L. and Ye, Y. and Wood, C.G. and Pu, X. and Mazur, A.M. and Boulygina, E.S. and Chekanov, N.N. and Foglio, M. and Lechner, D. and Gut, I. and Heath, S. and Blanche, H. and Skryabin, K.G. and McKay, J.D. and Rothman, N. and Lathrop, M. and Brennan, P. and Saunders, B. and Thomas, H. and Clark, S. and Tomlinson, I.
- Subjects
Male ,pathogenesi ,genetic association ,phenotype ,Adenomatous Polyposis Coli Protein ,colorectal cancer ,Colorectal Neoplasm ,cancer risk ,gene frequency ,Polymorphism, Single Nucleotide ,Article ,DNA glycosyltransferase, adult ,DNA glycosylase MutY ,colon polyposi ,single nucleotide polymorphism ,genetic variability ,middle aged ,controlled study ,Genetic Predisposition to Disease ,human ,DNA Glycosylase ,Germ-Line Mutation ,Aged ,colorectal adenoma ,Allele ,modifier gene ,Genes, Modifier ,disease predisposition ,APC protein, human ,major clinical study ,digestive system diseases ,human tissue ,APC protein ,female ,priority journal ,Adenomatous Polyposis Coli ,germline mutation ,familial colon polyposi ,adenoma ,single nucleotide polymorphism, Adenoma ,genetic ,genetic predisposition - Abstract
The presence of multiple (5-100) colorectal adenomas suggests an inherited predisposition, but the genetic aetiology of this phenotype is undetermined if patients test negative for Mendelian polyposis syndromes such as familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). We investigated whether 18 common colorectal cancer (CRC) predisposition single-nucleotide polymorphisms (SNPs) could help to explain some cases with multiple adenomas who phenocopied FAP or MAP, but had no pathogenic APC or MUTYH variant. No multiple adenoma case had an outlying number of CRC SNP risk alleles, but multiple adenoma patients did have a significantly higher number of risk alleles than population controls (P = 5.7 × 10-7). The association was stronger in those with ≥ 10 adenomas. The CRC SNPs accounted for 4.3% of the variation in multiple adenoma risk, with three SNPs (rs6983267, rs10795668, rs3802842) explaining 3.0% of the variation. In FAP patients, the CRC risk score did not differ significantly from the controls, as we expected given the overwhelming effect of pathogenic germline APC variants on the phenotype of these cases. More unexpectedly, we found no evidence that the CRC SNPs act as modifier genes for the number of colorectal adenomas in FAP patients. In conclusion, common colorectal tumour risk alleles contribute to the development of multiple adenomas in patients without pathogenic germline APC or MUTYH variants. This phenotype may have 'polygenic' or monogenic origins. The risk of CRC in relatives of multiple adenoma cases is probably much lower for cases with polygenic disease, and this should be taken into account when counselling such patients. © 2015 Macmillan Publishers Limited All rights reserved.
- Published
- 2015
5. Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer (vol 41, pg 991, 2009)
- Author
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Wu, X, Ye, Y, Kiemeney, L, Sulem, P, Rafnar, T, Matullo, G, Seminara, D, Yoshida, T, Saeki, N, Andrew, A, Dinney, C, Czerniak, B, Zhang, Z, Kiltie, A, Bishop, D, Vineis, P, Porru, S, Buntinx, F, Kellen, E, Zeegers, M, Kumar, R, Rudnai, P, Gurzau, E, Koppova, K, and Mayordomo, J
- Published
- 2016
6. Genome-wide association study of renal cell carcinoma identifiestwo susceptibility loci on 2p21 and 11q13.3
- Author
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Purdue MP, Johansson M, Zelenika D, Toro JR, Scelo G, Moore LE, Prokhortchouk E, Wu X, Kiemeney LA, Gaborieau V, Jacobs KB, Chow WH, Zaridze D, Matveev V, Lubinski J, Trubicka J, Szeszenia Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Bucur A, Bencko V, Foretova L, Janout V, Boffetta P, Colt JS, Davis FG, Schwartz KL, Banks RE, Selby PJ, Harnden P, Berg CD, Hsing AW, Grubb RL 3rd, Boeing H, Vineis P, Clavel Chapelon F, Palli D, Tumino R, Krogh V, Duell EJ, Quirós JR, Sanchez MJ, Navarro C, Ardanaz E, Dorronsoro M, Khaw KT, Allen NE, Bueno de Mesquita HB, Peeters PH, Trichopoulos D, Linseisen J, Ljungberg B, Overvad K, Tjønneland A, Romieu I, Riboli E, Mukeria A, Shangina O, Stevens VL, Thun MJ, Diver WR, Gapstur SM, Pharoah PD, Easton DF, Albanes D, Weinstein SJ, Virtamo J, Vatten L, Hveem K, Njølstad I, Tell GS, Stoltenberg C, Kumar R, Koppova K, Cussenot O, Benhamou S, Oosterwijk E, Vermeulen SH, Aben KK, van der Marel SL, Ye Y, Wood CG, Pu X, Mazur AM, Boulygina ES, Chekanov NN, Foglio M, Lechner D, Gut I, Heath S, Blanche H, Hutchinson A, Thomas G, Wang Z, Yeager M, Fraumeni JF Jr, Skryabin KG, McKay JD, Rothman N, Chanock SJ, Lathrop M, Brennan P., PANICO, SALVATORE, Purdue, Mp, Johansson, M, Zelenika, D, Toro, Jr, Scelo, G, Moore, Le, Prokhortchouk, E, Wu, X, Kiemeney, La, Gaborieau, V, Jacobs, Kb, Chow, Wh, Zaridze, D, Matveev, V, Lubinski, J, Trubicka, J, Szeszenia Dabrowska, N, Lissowska, J, Rudnai, P, Fabianova, E, Bucur, A, Bencko, V, Foretova, L, Janout, V, Boffetta, P, Colt, J, Davis, Fg, Schwartz, Kl, Banks, Re, Selby, Pj, Harnden, P, Berg, Cd, Hsing, Aw, Grubb RL, 3rd, Boeing, H, Vineis, P, Clavel Chapelon, F, Palli, D, Tumino, R, Krogh, V, Panico, Salvatore, Duell, Ej, Quirós, Jr, Sanchez, Mj, Navarro, C, Ardanaz, E, Dorronsoro, M, Khaw, Kt, Allen, Ne, Bueno de Mesquita, Hb, Peeters, Ph, Trichopoulos, D, Linseisen, J, Ljungberg, B, Overvad, K, Tjønneland, A, Romieu, I, Riboli, E, Mukeria, A, Shangina, O, Stevens, Vl, Thun, Mj, Diver, Wr, Gapstur, Sm, Pharoah, Pd, Easton, Df, Albanes, D, Weinstein, Sj, Virtamo, J, Vatten, L, Hveem, K, Njølstad, I, Tell, G, Stoltenberg, C, Kumar, R, Koppova, K, Cussenot, O, Benhamou, S, Oosterwijk, E, Vermeulen, Sh, Aben, Kk, van der Marel, Sl, Ye, Y, Wood, Cg, Pu, X, Mazur, Am, Boulygina, E, Chekanov, Nn, Foglio, M, Lechner, D, Gut, I, Heath, S, Blanche, H, Hutchinson, A, Thomas, G, Wang, Z, Yeager, M, Fraumeni JF, Jr, Skryabin, Kg, Mckay, Jd, Rothman, N, Chanock, Sj, Lathrop, M, and Brennan, P.
- Published
- 2011
7. A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer
- Author
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Kiemeney, La, Sulem, P, Besenbacher, S, Vermeulen, Sh, Sigurdsson, A, Thorleifsson, G, Stacey, Sn, Gudmundsson, J, Zanon, C, Kostic, J, Bjarnason, H, Palsson, St, Skarpheoinsson, Ob, Gudjonsson, Sa, Witjes, Ja, Grotenhuis, Aj, Vehaegh, Gw, Bishop, Dt, CHUNG SAK, S, Choudhury, A, Elliott, F, Barrett, Jh, Hurst, Cd, DE VERDIER PK, Rudnai, P, Gurzau, E, Koppova, K, Vineis, P, Polidoro, S, Guarrera, S, Sacerdote, C, Campagna, Marcello, Placidi, Donatella, Arici, Cecilia, Zeegers, Mp, Kellen, E, SAEZ GUTIERREZ, B, SANZ VELEZ JI, SANCHEZ ZALABARDO, M, Valdivia, G, GARCIA PRATS MD, Hengstler, Jg, Blaszkewicz, M, Dietrich, H, Ophoff, Ra, VA DEN BERG LH, Aleiusdottir, K, Kristjansson, K, Geirsson, G, Nikulasson, S, Petursdottir, V, Kong, A, Thorgeirsson, T, Mungan, Na, Lindblom, A, VAN ES MA, Porru, Stefano, Buntinx, F, Golka, K, Mayordomo, Ji, Kumar, R, Matullo, G, Steineck, G, Kiltie, Ae, Aben, Kkh, Jonsson, E, Thorsteinsdottir, U, Knowles, Ma, Rafnar, T, and Stefansson, K.
- Published
- 2010
8. Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer (vol 41, pg 991, 2009)
- Author
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Wu, X, Ye, Y, Kiemeney, LA, Sulem, P, Rafnar, T, Matullo, G, Seminara, D, Yoshida, T, Saeki, N, Andrew, AS, Dinney, CP, Czerniak, B, Zhang, Z-F, Kiltie, AE, Bishop, DT, Vineis, P, Porru, S, Buntinx, F, Kellen, E, Zeegers, MP, Kumar, R, Rudnai, P, Gurzau, E, Koppova, K, Mayordomo, JI, Sanchez, M, Saez, B, Lindblom, A, de Verdier, P, Steineck, G, Mills, GB, Schned, A, Chang, S-C, Lin, J, Chang, DW, Hale, KS, Majewski, T, Grossman, HB, Thorlacius, S, Thorsteinsdottir, U, Aben, KKH, Witjes, JA, Stefansson, K, Amos, CI, Karagas, MR, Gu, J, Guarrera, S, and Polidoro, S
- Published
- 2009
9. Erratum: Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer (Nature Genetics) (2009) 41 (991-995))
- Author
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Wu, X, Ye, Y, Kiemeney, LA, Sulem, P, Rafnar, T, Matullo, G, Seminara, D, Yoshida, T, Saeki, N, Andrew, AS, Dinney, CP, Czerniak, B, Zhang, Z-F, Kiltie, AE, Bishop, DT, Vineis, P, Porru, S, Buntinx, F, Kellen, E, Zeegers, MP, Kumar, R, Rudnai, P, Gurzau, E, Koppova, K, Mayordomo, JI, Sanchez, M, Saez, B, Lindblom, A, De Verdier, P, Steineck, G, Mills, GB, Schned, A, Chang, S-C, Lin, J, Chang, DW, Hale, KS, Majewski, T, Grossman, HB, Thorlacius, S, Thorsteinsdottir, U, Aben, KKH, Witjes, JA, Stefansson, K, Amos, CI, Karagas, MR, and Gu, J
- Published
- 2009
10. Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer
- Author
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Wu, X, Ye, Y, Kiemeney, La, Sulem, P, Rafnar, T, Matullo, G, Seminara, D, Yoshida, T, Saeki, N, Andrew, As, Dinney, Cp, Czerniak, B, Zhang, Z, Kiltie, Ae, Bishop, Dt, Vineis, P, Porru, Stefano, Buntinx, F, Kellen, E, Zeegers, Mp, Kumar, R, Rudnai, P, Gurzau, E, Koppova, K, Mayordomo, Ji, Sanchez, M, Saez, B, Lindblom, A, DE VERDIER, P, Steinek, G, Mills, Gb, Schned, A, Chang, Sc, Lin, J, Chang, Dw, Hale, Ks, Majewski, T, Grossman, Hb, Thorlacius, S, Thorsterindottir, U, Aben, Kkh, Witjes, Ja, Stefansson, K, Amos, Ci, Karagas, Mr, and Gu, J.
- Published
- 2009
11. Polymorphisms in DNA repair genes, smoking, and bladder cancer risk: findings from the International Consortium of Bladder Cancer
- Author
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Stern, Mc, Lin, J, Figueroa, Jd, Kelsey, Kt, Kiltie, Ae, Yuan, J. M., Matullo, G, Fletcher, T, Benhamou, S, Taylor, Ja, Placidi, Donatella, Zhang, Zf, Steineck, G, Rothman, N, Kogevinas, M, Silverman, D, Malatas, N, Chanock, S, Wu, X, KARAGAS MR ANDREW AS, Nelson, Hh, Bishop, Dt, Sak, Sc, Choudhury, A, Barrett, Jh, Elliot, F, Corral, R, Joshi, Ad, GAGO DOMINGUEZ, M, Cortessis, Vk, Xiang, Yb, Vineis, P, Sacerdote, C, Guarrera, S, Polidoro, S, Allione, A, Gurzau, E, Koppova, K, Kumar, R, Rudnai, P, Porru, Stefano, Carta, Angela, Campagna, Marcello, Arici, Cecilia, Park, Sl, and GARCIA CLOSAS, M.
- Published
- 2009
12. Long-Term Arsenic Exposure and Cancer Risk-Sensitivity to Choice of Indicators Based on Recent and Lifetime Arsenic Intake
- Author
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Fletcher, T, primary, Leonardi, G, additional, Hough, R, additional, Goessler, W, additional, Gurzau, E, additional, Koppova, K, additional, Rudnai, P, additional, Clemens, F, additional, Kumar, R, additional, and Vahter, M, additional
- Published
- 2006
- Full Text
- View/download PDF
13. CONSISTENCY AND HETEROGENEITY IN PM10 AND NO2 EFFECTS ON CHILDRENʼS RESPIRATORY SYMPTOMS
- Author
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Fletcher, T, primary, Pattenden, S, additional, Antova, T, additional, Braun-Fahrländer, Ch, additional, Koppova, K, additional, Forastiere, F, additional, Furman, V, additional, Gibson, H, additional, Heinrich, J, additional, Hoek, G, additional, Houthuijs, D, additional, Boris, Katsnelson, additional, Manfred, Neuberger, additional, Peter, Rudnai, additional, Hana, Slachtova, additional, and Renata, Zlotkowska, additional
- Published
- 2005
- Full Text
- View/download PDF
14. ARSENIC AND CANCER IN CENTRAL EUROPE
- Author
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Fletcher, T, primary, Leonardi, G, additional, Clemens, F, additional, Gurzau, E, additional, Koppova, K, additional, Rudnai, P, additional, Goessler, W, additional, Kumar, R, additional, and Vahter, M, additional
- Published
- 2005
- Full Text
- View/download PDF
15. A germline variant in the TP53 polyadenylation signal confers cancer susceptibility
- Author
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Rafnar, T., Tjø, nneland, A., Grasa, P., Mates, D., Jinga, V., Hansen, T., Sigurgeirsson, B., Nagore, E., Hemminki, K., Badescu, D., Panadero, A., Steinthorsdottir, V., Jø, rgensen, T., Rudnai, P., Mayordomo, Ji, Stacey, Sn, Helfand, Bt, Peters, Wh, Garcí, a-prats, Md, Lachance, Dh, Jenkins, Rb, Agnarsson, Ba, Gurzau, E., Sulem, P., Banasik, K., Masson, G., Thorisdottir, K., Constantinescu, V., Corredera, C., Rossum, Mm, Overvad, K., Requena, C., Ragnarsson, R., Kristjansdottir, S., Jonsson, T., Planelles, D., Fuertes, F., Badea, P., Mates, In, Johannsson, Ot, Jinga, M., Rice, T., Constantin, A., Wrensch, M., Sigurdsson, H., Spronsen, Dj, Hamdy, Fc, Kumar, R., Oort, Im, Johannsdottir, H., Tryggvadottir, L., Rivera, F., Stefansson, T., Dinu, DE, Keku, To, Moller, Ph, Kosel, Ml, Csiki, Ie, Gudjonsson, Sa, Benediktsdottir, Kr, Decker, Pa, Sandler, Rs, Aben, Kk, Pedersen, O., Wiencke, J., Soriano, V., Sanambrosio, E., Navarrete, S., Garcia, A., Jonsson, E., Barkardottir, Rb, Stefansson, K., Neal, DE, Gudbjartsson, Df, Juan, A., Donovan, Jl, Codreanu, O., Lindblom, A., Fuentelsaz, V., Gudmundsson, J., Witte, Dr, Kiemeney, La, Xiao, Y., Kong, A., Jonasdottir, A., Olafsson, Jh, Cremers, Rg, Nexø, Einarsson, Gv, Hansen, Hm, Helgadottir, Ht, Catalona, Wj, Magnusson, Ot, O Neill, Bp, Thorleifsson, G., Sigurdsson, F., Thorsteinsdottir, U., Valdimarsson, T., Vogel, U., Jonasson, Jg, Schalken, Ja, Sigurdsson, A., and Koppova, K.
16. Dual-color real-time telomeric repeat amplification protocol
- Author
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Jiri Fajkus, Koppova, K., and Kunicka, Z.
17. Smoking and metabolism phenotype interact with inorganic arsenic in causing bladder cancer
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Fletcher, T., Leonardi, G. S., Vahter, M., Goessler, W., Eugen Gurzau, Hemminki, K., Hough, R., Koppova, K., Kumar, R., Leonardi, G., and Rudnai, P.
18. Intake of inorganic arsenic from food in hungary, Romania and Slovakia
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Leonardi, G. S., Gnagnarella, P., Fletcher, T., Walter Goessler, Gurzau, E., Hemminki, K., Hough, R., Koppova, K., Kumar, R., Leonardi, G., Rudnai, P., and Vahter, M.
19. CONSISTENCY AND HETEROGENEITY IN PM10AND NO2EFFECTS ON CHILDREN'S RESPIRATORY SYMPTOMS
- Author
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Fletcher, T, Pattenden, S, Antova, T, Braun-Fahrländer, Ch, Koppova, K, Forastiere, F, Furman, V, Gibson, H, Heinrich, J, Hoek, G, Houthuijs, D, Boris, Katsnelson, Manfred, Neuberger, Peter, Rudnai, Hana, Slachtova, and Renata, Zlotkowska
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- 2005
20. Lifetime Exposure to Arsenic in Residential Drinking Water in Central Europe.
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Fletcher, T, Leonardi, G, Hough, R, Goessler, W, Gurzau, E, Koppova, K, Kumar, R, Rudnai, P, and Vahter, M
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- 2008
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21. Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3
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Jorge R. Toro, Vladimir Janout, Zhaoming Wang, Françoise Clavel-Chapelon, Petra H.M. Peeters, Paul Brennan, Camilla Stoltenberg, Hélène Blanché, Diana Zelenika, Vsevolod Matveev, Naomi E. Allen, Rosario Tumino, Vladimir Bencko, H. Bas Bueno-de-Mesquita, Lee E. Moore, María José Sánchez, Mark P. Purdue, Stephen J. Chanock, Kim Overvad, Kvetoslava Koppova, Joanne S. Colt, Eleonora Fabianova, Yuanqing Ye, Grethe S. Tell, Simon Heath, José Ramón Quirós, Egbert Oosterwijk, Amy Hutchinson, Jan Lubinski, Kristian Hveem, Peter Rudnai, Alexandru Bucur, Elio Riboli, James McKay, Ivo Gut, Paolo Vineis, Rosamonde E. Banks, Douglas F. Easton, Jarmo Virtamo, Wong-Ho Chow, Neonila Szeszenia-Dabrowska, Isabelle Romieu, Mark Lathrop, Demetrius Albanes, Kevin B. Jacobs, Sita H. Vermeulen, Egor Prokhortchouk, Carmen Navarro, Ann W. Hsing, Doris Lechner, M. Dorronsoro, Kendra Schwartz, Konstantin G. Skryabin, Mattias Johansson, Eric J. Duell, Valerie Gaborieau, W. Ryan Diver, Susan M. Gapstur, Börje Ljungberg, Dimitrios Trichopoulos, Paul D.P. Pharoah, Gilles Thomas, Victoria L. Stevens, Paolo Boffetta, Vittorio Krogh, David Zaridze, Lambertus A. Kiemeney, Joseph F. Fraumeni, Eugenia S. Boulygina, Kay-Tee Khaw, Olivier Cussenot, Heiner Boeing, Nathaniel Rothman, Michael J. Thun, Saskia S. L. van der Marel, Anush Mukeria, Alexander M. Mazur, Salvatore Panico, Peter Selby, Ghislaine Scelo, Faith G. Davis, Simone Benhamou, Joanna Trubicka, Christine D. Berg, Anne Tjønneland, Eva Ardanaz, Jolanta Lissowska, Katja K.H. Aben, Xifeng Wu, Rajesh Kumar, Jakob Linseisen, Nikolai N. Chekanov, Domenico Palli, Stephanie J. Weinstein, Inger Njølstad, Mario Foglio, Lars J. Vatten, Meredith Yeager, Xia Pu, Robert L. Grubb, Oxana Shangina, Christopher G. Wood, Patricia Harnden, Lenka Foretova, Purdue, M.P., Johansson, M., Zelenika, D., Toro, J.R., Scelo, G., Moore, L.E., Prokhortchouk, E., Wu, X., Kiemeney, L.A., Gaborieau, V., Jacobs, K.B., Chow, W.-H., Zaridze, D., Matveev, V., Lubinski, J., Trubicka, J., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Bucur, A., Bencko, V., Foretova, L., Janout, V., Boffetta, P., Colt, J.S., Davis, F.G., Schwartz, K.L., Banks, R.E., Selby, P.J., Harnden, P., Berg, C.D., Hsing, A.W., Grubb, R.L., Boeing, H., Vineis, P., Clavel-Chapelon, F., Palli, D., Tumino, R., Krogh, V., Panico, S., Duell, E.J., Quiós, J.R., Sanchez, M.-J., Navarro, C., Ardanaz, E., Dorronsoro, M., Khaw, K.-T., Allen, N.E., Bueno-De-Mesquita, H.B., Peeters, P.H.M., Trichopoulos, D., Linseisen, J., Ljungberg, B., Overvad, K., Tjønneland, A., Romieu, I., Riboli, E., Mukeria, A., Shangina, O., Stevens, V.L., Thun, M.J., Diver, W.R., Gapstur, S.M., Pharoah, P.D., Easton, D.F., Albanes, D., Weinstein, S.J., Virtamo, J., Vatten, L., Hveem, K., Njølstad, I., Tell, G.S., Stoltenberg, C., Kumar, R., Koppova, K., Cussenot, O., Benhamou, S., Oosterwijk, E., Vermeulen, S.H., Aben, K.K.H., Van Der Marel, S.L., Ye, Y., Wood, C.G., Pu, X., Mazur, A.M., Boulygina, E.S., Chekanov, N.N., Foglio, M., Lechner, D., Gut, I., Heath, S., Blanche, H., Hutchinson, A., Thomas, G., Wang, Z., Yeager, M., Fraumeni Jr., J.F., Skryabin, K.G., McKay, J.D., Rothman, N., Chanock, S.J., Lathrop, M., and Brennan, P.
- Subjects
Genetics and epigenetic pathways of disease [NCMLS 6] ,Single-nucleotide polymorphism ,Locus (genetics) ,Genome-wide association study ,Biology ,carcinoma ,association study ,Genome ,Polymorphism, Single Nucleotide ,susceptibility ,Article ,Càncer de ronyó ,Genomic disorders and inherited multi-system disorders [IGMD 3] ,Molecular epidemiology [NCEBP 1] ,03 medical and health sciences ,0302 clinical medicine ,Gene mapping ,Risk Factors ,Genetics ,Humans ,Genetic Predisposition to Disease ,Genome-wide ,Gene ,Carcinoma, Renal Cell ,030304 developmental biology ,11q13.3 ,Molecular epidemiology Aetiology, screening and detection [NCEBP 1] ,0303 health sciences ,Genome, Human ,Chromosomes, Human, Pair 11 ,Kidney cancer ,Genomics ,2p21 ,SCARB1 ,Kidney Neoplasms ,3. Good health ,Genòmica ,030220 oncology & carcinogenesis ,Case-Control Studies ,Chromosomes, Human, Pair 2 ,loci ,Human genome ,renal ,Genome-Wide Association Study - Abstract
Contains fulltext : 97937.pdf (Publisher’s version ) (Closed access) We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r(2) = 0.99 in controls), rs11894252 (P = 1.8 x 10) and rs7579899 (P = 2.3 x 10), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 x 10(1)). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 x 10). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.
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- 2011
22. A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci
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Rajesh Kumar, Gerald L. Andriole, Robert L. Grubb, Monica McGrath, Amanda Black, Manuela Gago-Dominguez, Margaret A. Knowles, Francisco X. Real, Nilanjan Chatterjee, Thorunn Rafnar, Kevin B. Jacobs, Silvia Polidoro, Debra T. Silverman, Sita H. Vermeulen, Manuel Sanchez, Núria Malats, Salvatore Panico, Amy Hutchinson, William Wheeler, Carmen Navarro, Montserrat Garcia-Closas, Carlotta Sacerdote, Gabriel Valdivia, Yi-Ping Fu, Kari Stefansson, Michelle A.T. Hildebrandt, Alessandra Allione, Katja K.H. Aben, Alison Johnson, W. Ryan Diver, Laurie Burdett, Sophia C.E. Bolick, David J. Hunter, Jarmo Virtamo, Jack A. Taylor, Ludmila Prokunina-Olsson, José I Sanz-Velez, Mark P. Purdue, Fulvio Ricceri, Elio Riboli, Maria Teresa Landi, Susan M. Gapstur, Søren Besenbacher, Joseph F. Fraumeni, Olivier Cussenot, J. Alfred Witjes, Victoria K. Cortessis, Paul Brennan, Tony Fletcher, David Van Den Berg, Börje Ljungberg, Lambertus A. Kiemeney, Dalsu Baris, Mark Teo, Zongli Xu, Geraldine Cancel-Tassin, Holger Dietrich, Zhaoming Wang, Maria D. Garcia-Prats, Françoise Clavel-Chapelon, Adonina Tardón, Paolo Vineis, Peter Rudnai, Margaret R. Karagas, Naomi E. Allen, H. Bas Bueno-de-Mesquita, Molly Schwenn, Jose I. Mayordomo, Ashley C. Godfrey, Manolis Kogevinas, Silvia Selinski, Stephen J. Chanock, Jonine D. Figueroa, Alan R. Schned, Stefano Porru, Mariana C. Stern, Demetrius Albanes, Simonetta Guarrera, Patrick Sulem, Immaculata De Vivo, Hushan Yang, Robert N. Hoover, Kvetoslava Koppova, Michael J. Thun, Malcolm C. Pike, Giuseppe Matullo, D T Bishop, Neil E. Caporaso, Klaus Golka, Eugen Gurzau, Colin P.N. Dinney, Josep Lloreta, Nathaniel Rothman, Eric J. Jacobs, Simone Benhamou, Alfredo Carrato, Federico Canzian, Xifeng Wu, Consol Serra, Anne Tjønneland, Jian-Min Yuan, Meredith Yeager, Reina García-Closas, Stephanie J. Weinstein, Jan G. Hengstler, Dimitrios Trichopoulos, Remco R. R. Makkinje, Anne E. Kiltie, Bogdan Czerniak, Meng Chen, Rothman, N, Garcia Closas, M, Chatterjee, N, Malats, N, Wu, X, Figueroa, Jd, Real, Fx, Van Den Berg, D, Matullo, G, Baris, D, Thun, M, Kiemeney, La, Vineis, P, De Vivo, I, Albanes, D, Purdue, Mp, Rafnar, T, Hildebrandt, Ma, Kiltie, Ae, Cussenot, O, Golka, K, Kumar, R, Taylor, Ja, Mayordomo, Ji, Jacobs, Kb, Kogevinas, M, Hutchinson, A, Wang, Z, Fu, Yp, Prokunina Olsson, L, Burdett, L, Yeager, M, Wheeler, W, Tardón, A, Serra, C, Carrato, A, García Closas, R, Lloreta, J, Johnson, A, Schwenn, M, Karagas, Mr, Schned, A, Andriole G., Jr, Grubb R., 3rd, Black, A, Jacobs, Ej, Diver, Wr, Gapstur, Sm, Weinstein, Sj, Virtamo, J, Cortessis, Vk, Gago Dominguez, M, Pike, Mc, Stern, Mc, Yuan, Jm, Hunter, Dj, Mcgrath, M, Dinney, Cp, Czerniak, B, Chen, M, Yang, H, Vermeulen, Sh, Aben, Kk, Witjes, Ja, Makkinje, Rr, Sulem, P, Besenbacher, S, Stefansson, K, Riboli, E, Brennan, P, Panico, Salvatore, Navarro, C, Allen, Ne, Bueno de Mesquita, Hb, Trichopoulos, D, Caporaso, Nicola, Landi, Mt, Canzian, F, Ljungberg, B, Tjonneland, A, Clavel Chapelon, F, Bishop, Dt, Teo, Mt, Knowles, Ma, Guarrera, S, Polidoro, S, Ricceri, F, Sacerdote, C, Allione, A, Cancel Tassin, G, Selinski, S, Hengstler, Jg, Dietrich, H, Fletcher, T, Rudnai, P, Gurzau, E, Koppova, K, Bolick, Sc, Godfrey, A, Xu, Z, Sanz Velez, Ji, D., García Prats M, Sanchez, M, Valdivia, G, Porru, S, Benhamou, S, Hoover, Rn, Fraumeni JF, Jr, Silverman, Dt, and Chanock, Sj
- Subjects
Male ,Arylamine N-Acetyltransferase ,Chromosomes, Human, Pair 22 ,Genome-wide association study ,Aetiology, screening and detection [ONCOL 5] ,medicine.disease_cause ,Genome-wide association studies ,Risk Factors ,genome-wide association ,bladder cancer ,Psychology ,Genetics ,Sex Characteristics ,Incidence ,Bladder cancer ,Smoking ,Chromosome Mapping ,Single Nucleotide ,Tag SNP ,Europe ,Chromosomes, Human, Pair 2 ,Pair 2 ,Female ,Human ,Locus (genetics) ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Risk Assessment ,Chromosomes ,Article ,Molecular epidemiology [NCEBP 1] ,Translational research [ONCOL 3] ,medicine ,Humans ,Family ,Genetic Predisposition to Disease ,Polymorphism ,Pair 18 ,Pair 22 ,Genome-Wide Association Study ,Neoplasm Staging ,Spain ,United States ,Urinary Bladder Neoplasms ,Cancer ,Chromosome ,medicine.disease ,Evaluation of complex medical interventions [NCEBP 2] ,Carcinogenesis ,Chromosomes, Human, Pair 18 - Abstract
We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.
- Published
- 2010
23. Application of fed-batch strategy to fully eliminate the negative effect of lignocellulose-derived inhibitors in ABE fermentation.
- Author
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Branska B, Koppova K, Husakova M, and Patakova P
- Abstract
Background: Inhibitors that are released from lignocellulose biomass during its treatment represent one of the major bottlenecks hindering its massive utilization in the biotechnological production of chemicals. This study demonstrates that negative effect of inhibitors can be mitigated by proper feeding strategy. Both, crude undetoxified lignocellulose hydrolysate and complex medium supplemented with corresponding inhibitors were tested in acetone-butanol-ethanol (ABE) fermentation using Clostridium beijerinckii NRRL B-598 as the producer strain., Results: First, it was found that the sensitivity of C. beijerinckii to inhibitors varied with different growth stages, being the most significant during the early acidogenic phase and less pronounced during late acidogenesis and early solventogenesis. Thus, a fed-batch regime with three feeding schemes was tested for toxic hydrolysate (no growth in batch mode was observed). The best results were obtained when the feeding of an otherwise toxic hydrolysate was initiated close to the metabolic switch, resulting in stable and high ABE production. Complete utilization of glucose, and up to 88% of xylose, were obtained. The most abundant inhibitors present in the alkaline wheat straw hydrolysate were ferulic and coumaric acids; both phenolic acids were efficiently detoxified by the intrinsic metabolic activity of clostridia during the early stages of cultivation as well as during the feeding period, thus preventing their accumulation. Finally, the best feeding strategy was verified using a TYA culture medium supplemented with both inhibitors, resulting in 500% increase in butanol titer over control batch cultivation in which inhibitors were added prior to inoculation., Conclusion: Properly timed sequential feeding effectively prevented acid-crash and enabled utilization of otherwise toxic substrate. This study unequivocally demonstrates that an appropriate biotechnological process control strategy can fully eliminate the negative effects of lignocellulose-derived inhibitors., (© 2024. The Author(s).)
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- 2024
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24. Sex specific associations in genome wide association analysis of renal cell carcinoma.
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Laskar RS, Muller DC, Li P, Machiela MJ, Ye Y, Gaborieau V, Foll M, Hofmann JN, Colli L, Sampson JN, Wang Z, Bacq-Daian D, Boland A, Abedi-Ardekani B, Durand G, Le Calvez-Kelm F, Robinot N, Blanche H, Prokhortchouk E, Skryabin KG, Burdett L, Yeager M, Radojevic-Skodric S, Savic S, Foretova L, Holcatova I, Janout V, Mates D, Rascu S, Mukeria A, Zaridze D, Bencko V, Cybulski C, Fabianova E, Jinga V, Lissowska J, Lubinski J, Navratilova M, Rudnai P, Świątkowska B, Benhamou S, Cancel-Tassin G, Cussenot O, Trichopoulou A, Riboli E, Overvad K, Panico S, Ljungberg B, Sitaram RT, Giles GG, Milne RL, Severi G, Bruinsma F, Fletcher T, Koppova K, Larsson SC, Wolk A, Banks RE, Selby PJ, Easton DF, Pharoah P, Andreotti G, Beane Freeman LE, Koutros S, Albanes D, Männistö S, Weinstein S, Clark PE, Edwards TL, Lipworth L, Carol H, Freedman ML, Pomerantz MM, Cho E, Kraft P, Preston MA, Wilson KM, Michael Gaziano J, Sesso HD, Black A, Freedman ND, Huang WY, Anema JG, Kahnoski RJ, Lane BR, Noyes SL, Petillo D, Teh BT, Peters U, White E, Anderson GL, Johnson L, Luo J, Chow WH, Moore LE, Choueiri TK, Wood C, Johansson M, McKay JD, Brown KM, Rothman N, Lathrop MG, Deleuze JF, Wu X, Brennan P, Chanock SJ, Purdue MP, and Scelo G
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- Computational Biology, Female, Humans, Male, Odds Ratio, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Factors, Carcinoma, Renal Cell epidemiology, Carcinoma, Renal Cell genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Kidney Neoplasms epidemiology, Kidney Neoplasms genetics
- Abstract
Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (OR
male ) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale ) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.- Published
- 2019
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25. Telomere length, arsenic exposure and risk of basal cell carcinoma of skin.
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Srinivas N, Rachakonda S, Hielscher T, Calderazzo S, Rudnai P, Gurzau E, Koppova K, Fletcher T, and Kumar R
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- Aged, Case-Control Studies, Female, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Arsenic toxicity, Carcinoma, Basal Cell chemically induced, Carcinoma, Basal Cell genetics, Environmental Exposure, Genetic Predisposition to Disease, Skin Neoplasms chemically induced, Skin Neoplasms genetics, Telomere drug effects
- Abstract
Telomere length per se a heritable trait has been reported to be associated with different diseases including cancers. In this study, based on arsenic-exposed 528 cases with basal cell carcinoma (BCC) of skin and 533 healthy controls, we investigated effect of telomere length, measured by real-time PCR, on the disease risk. We observed a statistically significant association between decreased telomere length and increased BCC risk [odds ratio (OR) = 5.92, 95% confidence interval (CI) = 3.92 to 9.01, P < 0.0001]. Due to confounder effect of arsenic exposure, in a two-sample Mendelian randomization (MR), telomere length associated single-nucleotide polymorphisms as instrument variables violated valid assumptions; however, one-sample MR adjusted for arsenic exposure indicated an increased risk of BCC with short telomeres. The interaction between arsenic exposure and telomere length on BCC risk was statistically significant (P = 0.02). Within each tertile based on arsenic exposure, the individuals with shorter telomeres were at an increased risk of BCC, with highest risk being in the highest exposed group (OR = 16.13, 95% CI = 6.71 to 40.00, P < 0.0001), followed by those in medium exposure group and low exposure group. The combined effect of highest arsenic exposure and shortest telomeres on BCC risk (OR = 10.56, 95% CI = 5.14 to 21.70) showed a statistically significant departure from additivity (interaction contrast ratio 6.56, P = 0.03). Our results show that in the presence of arsenic exposure, decreased telomere length predisposes individuals to increased risk of BCC, with the effect being synergistic in individuals with highest arsenic exposure and shortest telomeres., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2019
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26. Corrigendum re "Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma" [Eur Urol 2017;72:747-54].
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Machiela MJ, Hofmann JN, Carreras-Torres R, Brown KM, Johansson M, Wang Z, Foll M, Li P, Rothman N, Savage SA, Gaborieau V, McKay JD, Ye Y, Henrion M, Bruinsma F, Jordan S, Severi G, Hveem K, Vatten LJ, Fletcher T, Koppova K, Larsson SC, Wolk A, Banks RE, Selby PJ, Easton DF, Pharoah P, Andreotti G, Freeman LEB, Koutros S, Albanes D, Mannisto S, Weinstein S, Clark PE, Edwards TE, Lipworth L, Gapstur SM, Stevens VL, Carol H, Freedman ML, Pomerantz MM, Cho E, Kraft P, Preston MA, Wilson KM, Gaziano JM, Sesso HS, Black A, Freedman ND, Huang WY, Anema JG, Kahnoski RJ, Lane BR, Noyes SL, Petillo D, Colli LM, Sampson JN, Besse C, Blanche H, Boland A, Burdette L, Prokhortchouk E, Skryabin KG, Yeager M, Mijuskovic M, Ognjanovic M, Foretova L, Holcatova I, Janout V, Mates D, Mukeriya A, Rascu S, Zaridze D, Bencko V, Cybulski C, Fabianova E, Jinga V, Lissowska J, Lubinski J, Navratilova M, Rudnai P, Szeszenia-Dabrowska N, Benhamou S, Cancel-Tassin G, Cussenot O, Bueno-de-Mesquita HBA, Canzian F, Duell EJ, Ljungberg B, Sitaram RT, Peters U, White E, Anderson GL, Johnson L, Luo J, Buring J, Lee IM, Chow WH, Moore LE, Wood C, Eisen T, Larkin J, Choueiri TK, Lathrop GM, Teh BT, Deleuze JF, Wu X, Houlston RS, Brennan P, Chanock SJ, Scelo G, and Purdue MP
- Published
- 2018
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27. Platinum, palladium, rhodium, molybdenum and strontium in blood of urban women in nine countries.
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Rentschler G, Rodushkin I, Cerna M, Chen C, Harari F, Harari R, Horvat M, Hruba F, Kasparova L, Koppova K, Krskova A, Krsnik M, Laamech J, Li YF, Löfmark L, Lundh T, Lundström NG, Lyoussi B, Mazej D, Osredkar J, Pawlas K, Pawlas N, Prokopowicz A, Skerfving S, Snoj Tratnik J, Spevackova V, Spiric Z, Sundkvist A, Strömberg U, Vadla D, Wranova K, Zizi S, and Bergdahl IA
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- Cities, Female, Humans, Middle Aged, Molybdenum blood, Palladium blood, Platinum blood, Rhodium blood, Strontium blood, Environmental Monitoring, Metals, Heavy blood
- Abstract
Background: There is little reliable information on human exposure to the metals platinum (Pt), palladium (Pd) and rhodium (Rh), despite their use in enormous quantities in catalytic converters for automobile exhaust systems., Objectives: To evaluate blood concentrations of Pt (B-Pt), Pd (B-Pd) and Rh (B-Rh) in women from six European and three non-European countries, and to identify potentially influential factors. In addition, molybdenum (Mo) and strontium (Sr) were analysed., Methods: Blood from 248 women aged 47-61 was analysed by high resolution inductively coupled plasma mass spectrometry under strict quality control., Results: The medians were: B-Pt 0.8 (range <0.6-5.2), B-Pd <5 (<5-9.3), B-Rh <0.4 (<0.4-3.6)ng/L and B-Mo 2.0 (0.2-16) and B-Sr 16.6 (3.5-49) μg/L. Two women with highly elevated B-Pt (242 and 60ng/L), previously cancer treated with cis-platinum, were not included in the data analysis. All elements varied geographically (2-3 times) (B-Pd P=0.05; all other elements P<0.001); variations within each area were generally 5-10 times. Traffic was not associated with increased concentrations., Conclusions: General population blood concentrations of Pt, Pd and Rh are within or below the single digit ng/L range, much lower than in most previous reports. This is probably due to improved analytical performance, allowing for more reliable information at ultra-trace levels. In general, Mo and Sr agreed with previously reported concentrations. All elements showed geographical and inter-individual variations, but no convincing relationships with self-reported traffic intensity were found. Pt from the antineoplastic drug cis-platinum is retained in the body for years., (Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.)
- Published
- 2018
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28. Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma.
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Machiela MJ, Hofmann JN, Carreras-Torres R, Brown KM, Johansson M, Wang Z, Foll M, Li P, Rothman N, Savage SA, Gaborieau V, McKay JD, Ye Y, Henrion M, Bruinsma F, Jordan S, Severi G, Hveem K, Vatten LJ, Fletcher T, Koppova K, Larsson SC, Wolk A, Banks RE, Selby PJ, Easton DF, Pharoah P, Andreotti G, Freeman LEB, Koutros S, Albanes D, Mannisto S, Weinstein S, Clark PE, Edwards TE, Lipworth L, Gapstur SM, Stevens VL, Carol H, Freedman ML, Pomerantz MM, Cho E, Kraft P, Preston MA, Wilson KM, Gaziano JM, Sesso HS, Black A, Freedman ND, Huang WY, Anema JG, Kahnoski RJ, Lane BR, Noyes SL, Petillo D, Colli LM, Sampson JN, Besse C, Blanche H, Boland A, Burdette L, Prokhortchouk E, Skryabin KG, Yeager M, Mijuskovic M, Ognjanovic M, Foretova L, Holcatova I, Janout V, Mates D, Mukeriya A, Rascu S, Zaridze D, Bencko V, Cybulski C, Fabianova E, Jinga V, Lissowska J, Lubinski J, Navratilova M, Rudnai P, Szeszenia-Dabrowska N, Benhamou S, Cancel-Tassin G, Cussenot O, Bueno-de-Mesquita HB, Canzian F, Duell EJ, Ljungberg B, Sitaram RT, Peters U, White E, Anderson GL, Johnson L, Luo J, Buring J, Lee IM, Chow WH, Moore LE, Wood C, Eisen T, Larkin J, Choueiri TK, Lathrop GM, Teh BT, Deleuze JF, Wu X, Houlston RS, Brennan P, Chanock SJ, Scelo G, and Purdue MP
- Subjects
- Carcinoma, Renal Cell blood, Carcinoma, Renal Cell pathology, Case-Control Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Kidney Neoplasms blood, Kidney Neoplasms pathology, Leukocytes chemistry, Mendelian Randomization Analysis, Odds Ratio, Phenotype, Risk Assessment, Risk Factors, Telomere pathology, Carcinoma, Renal Cell genetics, Kidney Neoplasms genetics, Polymorphism, Single Nucleotide, Telomere genetics, Telomere Homeostasis
- Abstract
Background: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings., Objective: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations., Design, Setting, and Participants: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length., Outcome Measurements and Statistical Analysis: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis., Results and Limitations: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R
2 >0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13)., Conclusions: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk., Patient Summary: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma., (Published by Elsevier B.V.)- Published
- 2017
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29. Genome-wide association study identifies multiple risk loci for renal cell carcinoma.
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Scelo G, Purdue MP, Brown KM, Johansson M, Wang Z, Eckel-Passow JE, Ye Y, Hofmann JN, Choi J, Foll M, Gaborieau V, Machiela MJ, Colli LM, Li P, Sampson JN, Abedi-Ardekani B, Besse C, Blanche H, Boland A, Burdette L, Chabrier A, Durand G, Le Calvez-Kelm F, Prokhortchouk E, Robinot N, Skryabin KG, Wozniak MB, Yeager M, Basta-Jovanovic G, Dzamic Z, Foretova L, Holcatova I, Janout V, Mates D, Mukeriya A, Rascu S, Zaridze D, Bencko V, Cybulski C, Fabianova E, Jinga V, Lissowska J, Lubinski J, Navratilova M, Rudnai P, Szeszenia-Dabrowska N, Benhamou S, Cancel-Tassin G, Cussenot O, Baglietto L, Boeing H, Khaw KT, Weiderpass E, Ljungberg B, Sitaram RT, Bruinsma F, Jordan SJ, Severi G, Winship I, Hveem K, Vatten LJ, Fletcher T, Koppova K, Larsson SC, Wolk A, Banks RE, Selby PJ, Easton DF, Pharoah P, Andreotti G, Freeman LEB, Koutros S, Albanes D, Männistö S, Weinstein S, Clark PE, Edwards TL, Lipworth L, Gapstur SM, Stevens VL, Carol H, Freedman ML, Pomerantz MM, Cho E, Kraft P, Preston MA, Wilson KM, Michael Gaziano J, Sesso HD, Black A, Freedman ND, Huang WY, Anema JG, Kahnoski RJ, Lane BR, Noyes SL, Petillo D, Teh BT, Peters U, White E, Anderson GL, Johnson L, Luo J, Buring J, Lee IM, Chow WH, Moore LE, Wood C, Eisen T, Henrion M, Larkin J, Barman P, Leibovich BC, Choueiri TK, Mark Lathrop G, Rothman N, Deleuze JF, McKay JD, Parker AS, Wu X, Houlston RS, Brennan P, and Chanock SJ
- Subjects
- Adolescent, Adult, Aged, Female, Genetic Loci, Germ-Line Mutation, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, White People genetics, Young Adult, Carcinoma, Renal Cell genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Kidney Neoplasms genetics
- Abstract
Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10
-10 ), 3p22.1 (rs67311347, P=2.5 × 10-8 ), 3q26.2 (rs10936602, P=8.8 × 10-9 ), 8p21.3 (rs2241261, P=5.8 × 10-9 ), 10q24.33-q25.1 (rs11813268, P=3.9 × 10-8 ), 11q22.3 (rs74911261, P=2.1 × 10-10 ) and 14q24.2 (rs4903064, P=2.2 × 10-24 ). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.- Published
- 2017
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30. Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry.
- Author
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Figueroa JD, Middlebrooks CD, Banday AR, Ye Y, Garcia-Closas M, Chatterjee N, Koutros S, Kiemeney LA, Rafnar T, Bishop T, Furberg H, Matullo G, Golka K, Gago-Dominguez M, Taylor JA, Fletcher T, Siddiq A, Cortessis VK, Kooperberg C, Cussenot O, Benhamou S, Prescott J, Porru S, Dinney CP, Malats N, Baris D, Purdue MP, Jacobs EJ, Albanes D, Wang Z, Chung CC, Vermeulen SH, Aben KK, Galesloot TE, Thorleifsson G, Sulem P, Stefansson K, Kiltie AE, Harland M, Teo M, Offit K, Vijai J, Bajorin D, Kopp R, Fiorito G, Guarrera S, Sacerdote C, Selinski S, Hengstler JG, Gerullis H, Ovsiannikov D, Blaszkewicz M, Castelao JE, Calaza M, Martinez ME, Cordeiro P, Xu Z, Panduri V, Kumar R, Gurzau E, Koppova K, Bueno-De-Mesquita HB, Ljungberg B, Clavel-Chapelon F, Weiderpass E, Krogh V, Dorronsoro M, Travis RC, Tjønneland A, Brennan P, Chang-Claude J, Riboli E, Conti D, Stern MC, Pike MC, Van Den Berg D, Yuan JM, Hohensee C, Jeppson RP, Cancel-Tassin G, Roupret M, Comperat E, Turman C, De Vivo I, Giovannucci E, Hunter DJ, Kraft P, Lindstrom S, Carta A, Pavanello S, Arici C, Mastrangelo G, Kamat AM, Zhang L, Gong Y, Pu X, Hutchinson A, Burdett L, Wheeler WA, Karagas MR, Johnson A, Schned A, Monawar Hosain GM, Schwenn M, Kogevinas M, Tardón A, Serra C, Carrato A, García-Closas R, Lloreta J, Andriole G Jr, Grubb R 3rd, Black A, Diver WR, Gapstur SM, Weinstein S, Virtamo J, Haiman CA, Landi MT, Caporaso NE, Fraumeni JF Jr, Vineis P, Wu X, Chanock SJ, Silverman DT, Prokunina-Olsson L, and Rothman N
- Subjects
- Biomarkers, Tumor genetics, Case-Control Studies, Female, Genetic Association Studies, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Polymorphism, Single Nucleotide, Risk Factors, Urinary Bladder Neoplasms ethnology, Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 20, Urinary Bladder Neoplasms genetics, White People genetics
- Abstract
Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer., (Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)
- Published
- 2016
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31. New basal cell carcinoma susceptibility loci.
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Stacey SN, Helgason H, Gudjonsson SA, Thorleifsson G, Zink F, Sigurdsson A, Kehr B, Gudmundsson J, Sulem P, Sigurgeirsson B, Benediktsdottir KR, Thorisdottir K, Ragnarsson R, Fuentelsaz V, Corredera C, Gilaberte Y, Grasa M, Planelles D, Sanmartin O, Rudnai P, Gurzau E, Koppova K, Nexø BA, Tjønneland A, Overvad K, Jonasson JG, Tryggvadottir L, Johannsdottir H, Kristinsdottir AM, Stefansson H, Masson G, Magnusson OT, Halldorsson BV, Kong A, Rafnar T, Thorsteinsdottir U, Vogel U, Kumar R, Nagore E, Mayordomo JI, Gudbjartsson DF, Olafsson JH, and Stefansson K
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Child, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Iceland, Male, Membrane Proteins, Middle Aged, N-Myc Proto-Oncogene Protein, White People genetics, Young Adult, Carcinoma, Basal Cell genetics, Caspase 8 genetics, GATA3 Transcription Factor genetics, Homeodomain Proteins genetics, Nuclear Proteins genetics, Oncogene Proteins genetics, Proteins genetics, Skin Neoplasms genetics, Transcription Factors genetics
- Abstract
In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10(-12)), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10(-9)), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10(-12)) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10(-16)). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained.
- Published
- 2015
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32. Genetic variation in arsenic (+3 oxidation state) methyltransferase (AS3MT), arsenic metabolism and risk of basal cell carcinoma in a European population.
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Engström KS, Vahter M, Fletcher T, Leonardi G, Goessler W, Gurzau E, Koppova K, Rudnai P, Kumar R, and Broberg K
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Basal Cell epidemiology, Carcinoma, Basal Cell genetics, Case-Control Studies, Europe epidemiology, Female, Follow-Up Studies, Genotype, Humans, Male, Middle Aged, Polymerase Chain Reaction, Risk Factors, White People, Arsenic adverse effects, Arsenic metabolism, Carcinoma, Basal Cell chemically induced, Haplotypes genetics, Methyltransferases genetics, Polymorphism, Single Nucleotide genetics
- Abstract
Exposure to inorganic arsenic increases the risk of basal cell carcinoma (BCC). Arsenic metabolism is a susceptibility factor for arsenic toxicity, and specific haplotypes in arsenic (+3 oxidation state) methyltransferase (AS3MT) have been associated with increased urinary fractions of the most toxic arsenic metabolite, methylarsonic acid (MMA). The aim of this study is to elucidate the association of AS3MT haplotypes with arsenic metabolism and the risk of BCC. Four AS3MT polymorphisms were genotyped in BCC cases (N = 529) and controls (N = 533) from Eastern Europe with low to moderate arsenic exposure (lifetime average drinking water concentration: 1.3 µg/L, range 0.01-167 µg/L). Urinary metabolites [inorganic arsenic (iAs), MMA, dimethylarsinic acid (DMA)] were analyzed by HPLC-ICPMS. Five AS3MT haplotypes (based on rs3740400 A/C, rs3740393 G/C, rs11191439 T/C and rs1046778 T/C) had frequencies >5%. Individuals with the CCTC haplotype had lower %iAs (P = 0.032) and %MMA (P = 0.020) in urine, and higher %DMA (P = 0.033); individuals with the CGCT haplotype had higher %MMA (P < 0.001) and lower %DMA (P < 0.001). All haplotypes showed increased risk of BCC with increasing arsenic exposure through drinking water (ORs 1.1-1.4, P values from <0.001 to 0.082), except for the CCTC haplotype (OR 1.0, CI 0.9-1.2, P value 0.85). The results suggest that carriage of AS3MT haplotypes associated with less-efficient arsenic methylation, or lack of AS3MT haplotypes associated with a more-efficient arsenic methylation, results in higher risk of arsenic-related BCC. The fact that AS3MT haplotype status modified arsenic metabolism, and in turn the arsenic-related BCC risk, supports a causal relationship between low-level arsenic exposure and BCC., (© 2014 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.)
- Published
- 2015
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33. Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer.
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Rafnar T, Sulem P, Thorleifsson G, Vermeulen SH, Helgason H, Saemundsdottir J, Gudjonsson SA, Sigurdsson A, Stacey SN, Gudmundsson J, Johannsdottir H, Alexiusdottir K, Petursdottir V, Nikulasson S, Geirsson G, Jonsson T, Aben KK, Grotenhuis AJ, Verhaegh GW, Dudek AM, Witjes JA, van der Heijden AG, Vrieling A, Galesloot TE, De Juan A, Panadero A, Rivera F, Hurst C, Bishop DT, Sak SC, Choudhury A, Teo MT, Arici C, Carta A, Toninelli E, de Verdier P, Rudnai P, Gurzau E, Koppova K, van der Keur KA, Lurkin I, Goossens M, Kellen E, Guarrera S, Russo A, Critelli R, Sacerdote C, Vineis P, Krucker C, Zeegers MP, Gerullis H, Ovsiannikov D, Volkert F, Hengstler JG, Selinski S, Magnusson OT, Masson G, Kong A, Gudbjartsson D, Lindblom A, Zwarthoff E, Porru S, Golka K, Buntinx F, Matullo G, Kumar R, Mayordomo JI, Steineck DG, Kiltie AE, Jonsson E, Radvanyi F, Knowles MA, Thorsteinsdottir U, Kiemeney LA, and Stefansson K
- Subjects
- Adult, Aged, Aged, 80 and over, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Jagged-1 Protein, Male, Middle Aged, Polymorphism, Single Nucleotide, Serrate-Jagged Proteins, Calcium-Binding Proteins genetics, Chromosomes, Human, Pair 20 genetics, Intercellular Signaling Peptides and Proteins genetics, Membrane Proteins genetics, Urinary Bladder Neoplasms genetics, White People genetics
- Abstract
Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC cases and 10 456 controls. We tested a dataset containing 34.2 million variants, generated by imputation based on whole-genome sequencing of 2230 Icelanders. Several correlated variants at 20p12, represented by rs62185668, show genome-wide significant association with UBC after combining discovery and replication results (OR = 1.19, P = 1.5 × 10(-11) for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately 300 kb upstream from the JAG1 gene, an important component of the Notch signaling pathways that may be oncogenic or tumor suppressive in several forms of cancer. Our results add to the growing number of UBC risk variants discovered through GWAS., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2014
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34. Polymorphisms in DNA repair genes XRCC1 and XRCC3, occupational exposure to arsenic and sunlight, and the risk of non-melanoma skin cancer in a European case-control study.
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Surdu S, Fitzgerald EF, Bloom MS, Boscoe FP, Carpenter DO, Haase RF, Gurzau E, Rudnai P, Koppova K, Vahter M, Leonardi G, Goessler W, Kumar R, and Fletcher T
- Subjects
- Aged, Case-Control Studies, Europe epidemiology, Female, Humans, Male, Middle Aged, Neoplasms, Radiation-Induced chemically induced, Neoplasms, Radiation-Induced epidemiology, Neoplasms, Radiation-Induced etiology, Skin Neoplasms chemically induced, Skin Neoplasms etiology, Arsenic toxicity, DNA Repair genetics, Occupational Exposure, Polymorphism, Genetic, Skin Neoplasms epidemiology, Sunlight
- Abstract
X-ray repair cross-complementing group 1 (XRCC1) and group 3 (XRCC3) polymorphisms are relatively frequent in Caucasian populations and may have implications in skin cancer modulation. A few studies have evaluated their association with non-melanoma skin cancer (NMSC), but the results are inconsistent. In the current study, we aim to assess the impact of XRCC1 R399Q and XRCC3 T241M polymorphisms on the risk of NMSC associated with sunlight and arsenic exposure. Study participants consist of 618 new cases of NMSC and 527 hospital-based controls frequency matched on age, sex, and county of residence from Hungary, Romania, and Slovakia. Adjusted effects are estimated using multivariable logistic regression. The results indicate an increased risk of squamous cell carcinoma (SCC) for the homozygous variant genotype of XRCC1 R399Q (OR 2.53, 95% CI 1.14-5.65) and a protective effect against basal cell carcinoma (BCC) for the homozygous variant genotype of XRCC3 T241M (OR 0.61, 95% CI 0.41-0.92), compared with the respective homozygous common genotypes. Significant interactions are detected between XRCC3 T241M and sunlight exposure at work, and between XRCC3 T241M and exposure to arsenic in drinking water (p-value for interaction <0.10). In conclusion, the current study demonstrates that polymorphisms in XRCC genes may modify the associations between skin cancer risk and exposure to sunlight or arsenic. Given the high prevalence of genetic polymorphisms modifying the association between exposure to environmental carcinogens and NMSC, these results are of substantial relevance to public health., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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35. Germline sequence variants in TGM3 and RGS22 confer risk of basal cell carcinoma.
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Stacey SN, Sulem P, Gudbjartsson DF, Jonasdottir A, Thorleifsson G, Gudjonsson SA, Masson G, Gudmundsson J, Sigurgeirsson B, Benediktsdottir KR, Thorisdottir K, Ragnarsson R, Fuentelsaz V, Corredera C, Grasa M, Planelles D, Sanmartin O, Rudnai P, Gurzau E, Koppova K, Hemminki K, Nexø BA, Tjønneland A, Overvad K, Johannsdottir H, Helgadottir HT, Thorsteinsdottir U, Kong A, Vogel U, Kumar R, Nagore E, Mayordomo JI, Rafnar T, Olafsson JH, and Stefansson K
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Germ Cells metabolism, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Skin Neoplasms genetics, Young Adult, Antigens, Surface genetics, Carcinoma, Basal Cell genetics, GTP-Binding Protein Regulators genetics, Genetic Variation, Germ-Line Mutation, Transglutaminases genetics
- Abstract
To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide association study of 38.5 million single nucleotide polymorphisms (SNPs) and small indels identified through whole-genome sequencing of 2230 Icelanders. We imputed genotypes for 4208 BCC patients and 109 408 controls using Illumina SNP chip typing data, carried out association tests and replicated the findings in independent population samples. We found new BCC susceptibility loci at TGM3 (rs214782[G], P = 5.5 × 10(-17), OR = 1.29) and RGS22 (rs7006527[C], P = 8.7 × 10(-13), OR = 0.77). TGM3 encodes transglutaminase type 3, which plays a key role in production of the cornified envelope during epidermal differentiation.
- Published
- 2014
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36. Occupational exposure to arsenic and risk of nonmelanoma skin cancer in a multinational European study.
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Surdu S, Fitzgerald EF, Bloom MS, Boscoe FP, Carpenter DO, Haase RF, Gurzau E, Rudnai P, Koppova K, Févotte J, Vahter M, Leonardi G, Goessler W, Kumar R, and Fletcher T
- Subjects
- Adult, Aged, Case-Control Studies, Europe, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Risk Factors, Survival Rate, Arsenic adverse effects, Carcinoma, Basal Cell etiology, Carcinoma, Squamous Cell etiology, Environmental Exposure adverse effects, Occupational Exposure adverse effects, Skin Neoplasms etiology, Sunlight adverse effects
- Abstract
Occupational studies show a high risk of lung cancer related to arsenic exposure by inhalation; however, only a few studies, and with conflicting results, previously examined a potential link between arsenic exposure at work and skin cancer. The aim of this study is to assess airborne arsenic exposures at the workplace and to quantify associations with nonmelanoma skin cancer (NMSC). The study sample consists of 618 incident cases of NMSC and 527 hospital-based controls aged 30-79 years from Hungary, Romania and Slovakia. Exposures were evaluated by local experts using occupational histories. Information on host factors and other exposures was collected and used to adjust the associations of interest using multivariable logistic regression. The lifetime prevalence of exposure to work-related arsenic is 23.9% for cases and 15.5% for controls. No significant association between arsenic exposure in the workplace and NMSC was detected, although an increased adjusted odd ratio was observed for participants with higher cumulative lifetime workplace exposure to arsenic in dust and fumes compared to referents [odds ratios (OR) = 1.94, 95% confidence interval (CI) = 0.76-4.95]. There is evidence for modification of the workplace arsenic-NMSC association by work-related sunlight exposure in women, with a markedly increased adjusted OR in the presence of workplace sunlight exposure (OR = 10.22, 95% CI = 2.48-42.07). Workplace coexposure to arsenic and sunlight may thus pose an increased risk of NMSC., (© 2013 UICC.)
- Published
- 2013
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37. Occupational exposure to ultraviolet radiation and risk of non-melanoma skin cancer in a multinational European study.
- Author
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Surdu S, Fitzgerald EF, Bloom MS, Boscoe FP, Carpenter DO, Haase RF, Gurzau E, Rudnai P, Koppova K, Févotte J, Leonardi G, Vahter M, Goessler W, Kumar R, and Fletcher T
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Basal Cell epidemiology, Carcinoma, Basal Cell etiology, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell etiology, Case-Control Studies, Female, Humans, Hungary epidemiology, Male, Middle Aged, Odds Ratio, Risk, Romania epidemiology, Slovakia epidemiology, Occupational Exposure adverse effects, Skin Neoplasms epidemiology, Skin Neoplasms etiology, Ultraviolet Rays adverse effects
- Abstract
Background: Studies suggest that ambient sunlight plays an important role in the pathogenesis of non-melanoma skin cancers (NMSC). However, there is ongoing controversy regarding the relevance of occupational exposure to natural and artificial ultraviolet radiation (UV) radiation., Objectives: We investigated potential associations between natural and artificial UV radiation exposure at work with NMSC in a case-control study conducted in Hungary, Romania, and Slovakia., Methods: Occupational exposures were classified by expert assessment for 527 controls and 618 NMSC cases (515 basal cell carcinoma, BCC). Covariate information was collected via interview and multiple logistic regression models were used to assess associations between UV exposure and NMSC., Results: Lifetime prevalence of occupational exposure in the participants was 13% for natural UV radiation and 7% for artificial UV radiation. Significant negative associations between occupational exposure to natural UV radiation and NMSC were detected for all who had ever been exposed (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.27-0.80); similar results were detected using a semi-quantitative metric of cumulative exposure. The effects were modified by skin complexion, with significantly decreased risks of BCC among participants with light skin complexion. No associations were observed in relation to occupational artificial UV radiation exposure., Conclusions: The protective effect of occupational exposure to natural UV radiation was unexpected, but limited to light-skinned people, suggesting adequate sun-protection behaviors. Further investigations focusing on variations in the individual genetic susceptibility and potential interactions with environmental and other relevant factors are planned.
- Published
- 2013
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38. Cadmium, mercury and lead in the blood of urban women in Croatia, the Czech Republic, Poland, Slovakia, Slovenia, Sweden, China, Ecuador and Morocco.
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Pawlas N, Strömberg U, Carlberg B, Cerna M, Harari F, Harari R, Horvat M, Hruba F, Koppova K, Krskova A, Krsnik M, Li YF, Löfmark L, Lundh T, Lundström NG, Lyoussi B, Markiewicz-Górka I, Mazej D, Osredkar J, Pawlas K, Rentschler G, Spevackova V, Spiric Z, Sundkvist A, Tratnik JS, Vadla D, Zizi S, Skerfving S, and Bergdahl IA
- Subjects
- Croatia epidemiology, Czech Republic epidemiology, Ecuador epidemiology, Environmental Exposure analysis, Environmental Illness epidemiology, Female, Humans, Incidence, Middle Aged, Morocco epidemiology, Poland epidemiology, Slovakia epidemiology, Slovenia epidemiology, Sweden epidemiology, Cadmium blood, Environmental Illness blood, Lead blood, Mercury blood, Urban Population, Women's Health
- Abstract
Objectives: The aim of the study was to make an international comparison of blood levels of cadmium (B-Cd), lead (B-Pb) and mercury (B-Hg) of women in seven European, and three non-European cities, and to identify determinants., Materials and Methods: About 50 women (age: 46-62) from each city were recruited (totally 480) in 2006-2009. Interview and questionnaire data were obtained. Blood samples were analysed in one laboratory to avoid interlaboratory variation., Results: Between the European cities, the B-Pb and B-Cd results vary little (range of geometric means: 13.5-27.0 μg/l and 0.25-0.65 μg/l, respectively); the variation of B-Hg was larger (0.40-1.38 μg/l). Between the non-European cities the results for B-Pb, B-Cd and B-Hg were 19.2-68.0, 0.39-0.99 and 1.01-2.73 μg/l, respectively. Smoking was a statistically significant determinant for B-Cd, while fish and shellfish intakes contributed to B-Hg and B-Pb, amalgam fillings also contributed to B-Hg., Conclusions: The present results confirm the previous results from children; the exposure to lead and cadmium varies only little between different European cities suggesting that other factors than the living area are more important. The study also confirms the previous findings of higher cadmium and lead levels in some non-European cities. The geographical variation for mercury is significant.
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- 2013
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39. Inorganic arsenic and basal cell carcinoma in areas of Hungary, Romania, and Slovakia: a case-control study.
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Leonardi G, Vahter M, Clemens F, Goessler W, Gurzau E, Hemminki K, Hough R, Koppova K, Kumar R, Rudnai P, Surdu S, and Fletcher T
- Subjects
- Arsenic metabolism, Carcinoma, Basal Cell epidemiology, Case-Control Studies, Environmental Exposure, Hungary epidemiology, Logistic Models, Risk Assessment, Risk Factors, Romania epidemiology, Skin Neoplasms epidemiology, Slovakia epidemiology, Arsenic toxicity, Carcinoma, Basal Cell chemically induced, Skin Neoplasms chemically induced
- Abstract
Background: Inorganic arsenic (iAs) is a potent carcinogen, but there is a lack of information about cancer risk for concentrations < 100 μg/L in drinking water., Objectives: We aimed to quantify skin cancer relative risks in relation to iAs exposure < 100 μg/L and the modifying effects of iAs metabolism., Methods: The Arsenic Health Risk Assessment and Molecular Epidemiology (ASHRAM) study, a case-control study, was conducted in areas of Hungary, Romania, and Slovakia with reported presence of iAs in groundwater. Consecutively diagnosed cases of basal cell carcinoma (BCC) of the skin were histologically confirmed; controls were general surgery, orthopedic, and trauma patients who were frequency matched to cases by age, sex, and area of residence. Exposure indices were constructed based on information on iAs intake over the lifetime of participants. iAs metabolism status was classified based on urinary concentrations of methylarsonic acid (MA) and dimethylarsinic acid (DMA). Associations were estimated by multivariable logistic regression., Results: A total of 529 cases with BCC and 540 controls were recruited for the study. BCC was positively associated with three indices of iAs exposure: peak daily iAs dose rate, cumulative iAs dose, and lifetime average water iAs concentration. The adjusted odds ratio per 10-μg/L increase in average lifetime water iAs concentration was 1.18 (95% confidence interval: 1.08, 1.28). The estimated effect of iAs on cancer was stronger in participants with urinary markers indicating incomplete metabolism of iAs: higher percentage of MA in urine or a lower percentage of DMA., Conclusion: We found a positive association between BCC and exposure to iAs through drinking water with concentrations < 100 μg/L.
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- 2012
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40. A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23.
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Wu X, Scelo G, Purdue MP, Rothman N, Johansson M, Ye Y, Wang Z, Zelenika D, Moore LE, Wood CG, Prokhortchouk E, Gaborieau V, Jacobs KB, Chow WH, Toro JR, Zaridze D, Lin J, Lubinski J, Trubicka J, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Jinga V, Bencko V, Slamova A, Holcatova I, Navratilova M, Janout V, Boffetta P, Colt JS, Davis FG, Schwartz KL, Banks RE, Selby PJ, Harnden P, Berg CD, Hsing AW, Grubb RL 3rd, Boeing H, Vineis P, Clavel-Chapelon F, Palli D, Tumino R, Krogh V, Panico S, Duell EJ, Quirós JR, Sanchez MJ, Navarro C, Ardanaz E, Dorronsoro M, Khaw KT, Allen NE, Bueno-de-Mesquita HB, Peeters PH, Trichopoulos D, Linseisen J, Ljungberg B, Overvad K, Tjønneland A, Romieu I, Riboli E, Stevens VL, Thun MJ, Diver WR, Gapstur SM, Pharoah PD, Easton DF, Albanes D, Virtamo J, Vatten L, Hveem K, Fletcher T, Koppova K, Cussenot O, Cancel-Tassin G, Benhamou S, Hildebrandt MA, Pu X, Foglio M, Lechner D, Hutchinson A, Yeager M, Fraumeni JF Jr, Lathrop M, Skryabin KG, McKay JD, Gu J, Brennan P, and Chanock SJ
- Subjects
- Humans, Carcinoma, Renal Cell genetics, Chromosomes, Human, Pair 12, Genetic Predisposition to Disease, Genome-Wide Association Study, Kidney Neoplasms genetics
- Abstract
Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r(2) = 0.64, D ' = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10(-10) and P = 6.07 × 10(-9), respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR., (© The Author 2011. Published by Oxford University Press. All rights reserved.)
- Published
- 2012
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41. Interaction between functional polymorphic variants in cytokine genes, established risk factors and susceptibility to basal cell carcinoma of skin.
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Rizzato C, Canzian F, Rudnai P, Gurzau E, Stein A, Koppova K, Hemminki K, Kumar R, and Campa D
- Subjects
- Aged, Case-Control Studies, Female, Haplotypes, Humans, Male, Middle Aged, Oxidative Stress, Risk Factors, Carcinoma, Basal Cell genetics, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Skin Neoplasms genetics
- Abstract
Basal cell carcinoma (BCC) of the skin is the most common neoplasm among the Caucasian population of the Western world. Inflammation may result in oxidative stress and contribute to promotion and progression of tumors, including BCC. The role of cytokines, which are inflammatory modulators, in the biology of tumors has been extensively studied and it is well known that they are aberrantly produced by cancer cells, macrophages and other phagocytic cells. Genetic polymorphisms are known in several cytokine genes, which result in altered expression. In the present association study, we investigated the association of 14 functional polymorphisms in 11 cytokines genes with BCC risk in 529 BCC cases and 532 healthy controls. We have also tested the possible interactions between the genetic variants and three known risk factors for BCC: skin complexion, sun effect and skin response to sun exposure. We did not observe any statistically significant association between SNPs and BCC risk. However, we found that, in a subgroup of subjects more prone to skin burns, carriers of at least one copy of the G allele of rs1800629 (TNF) had an increased risk of BCC [odds ratio (OR) = 2.40, 95% confidence interval (CI) 1.38-4.16, P = 0.0005]. Moreover, in subjects less prone to sunburns, we observed that carriers of the C allele of rs1143627 (IL1B) showed a decreased risk (OR = 0.53, 95% CI 0.34-0.82, P = 0.0019). In conclusion, we found that two polymorphisms in inflammatory genes interacting with environmental risk factors could modulate BCC risk.
- Published
- 2011
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42. European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.
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Rafnar T, Vermeulen SH, Sulem P, Thorleifsson G, Aben KK, Witjes JA, Grotenhuis AJ, Verhaegh GW, Hulsbergen-van de Kaa CA, Besenbacher S, Gudbjartsson D, Stacey SN, Gudmundsson J, Johannsdottir H, Bjarnason H, Zanon C, Helgadottir H, Jonasson JG, Tryggvadottir L, Jonsson E, Geirsson G, Nikulasson S, Petursdottir V, Bishop DT, Chung-Sak S, Choudhury A, Elliott F, Barrett JH, Knowles MA, de Verdier PJ, Ryk C, Lindblom A, Rudnai P, Gurzau E, Koppova K, Vineis P, Polidoro S, Guarrera S, Sacerdote C, Panadero A, Sanz-Velez JI, Sanchez M, Valdivia G, Garcia-Prats MD, Hengstler JG, Selinski S, Gerullis H, Ovsiannikov D, Khezri A, Aminsharifi A, Malekzadeh M, van den Berg LH, Ophoff RA, Veldink JH, Zeegers MP, Kellen E, Fostinelli J, Andreoli D, Arici C, Porru S, Buntinx F, Ghaderi A, Golka K, Mayordomo JI, Matullo G, Kumar R, Steineck G, Kiltie AE, Kong A, Thorsteinsdottir U, Stefansson K, and Kiemeney LA
- Subjects
- Adult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 18 genetics, Disease Progression, Female, Genetic Loci genetics, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide genetics, Reproducibility of Results, Risk Factors, Young Adult, Urea Transporters, Genetic Predisposition to Disease, Genome-Wide Association Study, Membrane Transport Proteins genetics, Urinary Bladder Neoplasms genetics, White People genetics
- Abstract
Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.
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- 2011
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43. A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
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Stacey SN, Sulem P, Jonasdottir A, Masson G, Gudmundsson J, Gudbjartsson DF, Magnusson OT, Gudjonsson SA, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Nexø BA, Tjønneland A, Overvad K, Rudnai P, Gurzau E, Koppova K, Hemminki K, Corredera C, Fuentelsaz V, Grasa P, Navarrete S, Fuertes F, García-Prats MD, Sanambrosio E, Panadero A, De Juan A, Garcia A, Rivera F, Planelles D, Soriano V, Requena C, Aben KK, van Rossum MM, Cremers RG, van Oort IM, van Spronsen DJ, Schalken JA, Peters WH, Helfand BT, Donovan JL, Hamdy FC, Badescu D, Codreanu O, Jinga M, Csiki IE, Constantinescu V, Badea P, Mates IN, Dinu DE, Constantin A, Mates D, Kristjansdottir S, Agnarsson BA, Jonsson E, Barkardottir RB, Einarsson GV, Sigurdsson F, Moller PH, Stefansson T, Valdimarsson T, Johannsson OT, Sigurdsson H, Jonsson T, Jonasson JG, Tryggvadottir L, Rice T, Hansen HM, Xiao Y, Lachance DH, O Neill BP, Kosel ML, Decker PA, Thorleifsson G, Johannsdottir H, Helgadottir HT, Sigurdsson A, Steinthorsdottir V, Lindblom A, Sandler RS, Keku TO, Banasik K, Jørgensen T, Witte DR, Hansen T, Pedersen O, Jinga V, Neal DE, Catalona WJ, Wrensch M, Wiencke J, Jenkins RB, Nagore E, Vogel U, Kiemeney LA, Kumar R, Mayordomo JI, Olafsson JH, Kong A, Thorsteinsdottir U, Rafnar T, and Stefansson K
- Subjects
- Humans, Polymorphism, Single Nucleotide, Tumor Suppressor Protein p53 genetics, Genetic Predisposition to Disease, Germ-Line Mutation, Neoplasms genetics, Tumor Suppressor Protein p53 metabolism
- Abstract
To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
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- 2011
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44. POMC and TP53 genetic variability and risk of basal cell carcinoma of skin: Interaction between host and genetic factors.
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Rizzato C, Scherer D, Rudnai P, Gurzau E, Koppova K, Hemminki K, Canzian F, Kumar R, and Campa D
- Subjects
- Aged, Case-Control Studies, Europe, Female, Gene Frequency, Genetic Predisposition to Disease, Haplotypes, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Receptor, Melanocortin, Type 1 genetics, Risk Assessment, Risk Factors, Carcinoma, Basal Cell genetics, Polymorphism, Single Nucleotide, Pro-Opiomelanocortin genetics, Skin Neoplasms genetics, Skin Pigmentation, Tumor Suppressor Protein p53 genetics, Ultraviolet Rays adverse effects
- Abstract
Background: Basal cell carcinoma (BCC) of the skin is the most common neoplasm among the Caucasian population of the western world. Ultraviolet (UV) radiation-induced p53 activation promotes cutaneous pigmentation by increasing transcriptional activity of pro-opiomelanocortin (POMC) in the skin. Induction of POMC/α-melanocyte-stimulating hormone (α-MSH) activates the melanocortin 1 receptor (MC1R), resulting in skin pigmentation. The tumor suppressor p53 is a key player in stress responses that preserve genomic stability, responding to a variety of insults including DNA damage, hypoxia, metabolic stress and oncogene activation. Malfunction of the p53 pathway is an almost universal hallmark of human tumors. Polymorphisms in the gene encoding p53 (TP53) alter its transcriptional activity, which in turn may influence the UV radiation-induced tanning response., Objective: The aim of the present work is to test association between POMC and TP53 genetic variability, the possible interplay with host factors and the risk of basal cell carcinoma of skin., Methods: We covered the variability of the two genes we used 17 tagging polymorphisms in 529 BCC cases and 532 healthy controls. We have also tested the possible interactions between the genetic variants and three known risk factors for BCC: skin complexion, sun effect and skin response to sun exposure., Results: We did not observe any statistically significant association between SNPs in these two genes and BCC risk overall, nor interactions of SNPs with known BCC risk factors. However we found that, in the group of subjects with lower sun exposure, carriers of one copy of the C allele of the TP53 SNP rs12951053 had a decreased risk of BCC (OR=0.28, 95% CI 0.12-0.62, P=0.002)., Conclusions: We have observed that the interplay of an environmental risk factor and one polymorphism in TP53 gene could modulate the risk of BCC., (Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2011
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45. Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3.
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Purdue MP, Johansson M, Zelenika D, Toro JR, Scelo G, Moore LE, Prokhortchouk E, Wu X, Kiemeney LA, Gaborieau V, Jacobs KB, Chow WH, Zaridze D, Matveev V, Lubinski J, Trubicka J, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Bucur A, Bencko V, Foretova L, Janout V, Boffetta P, Colt JS, Davis FG, Schwartz KL, Banks RE, Selby PJ, Harnden P, Berg CD, Hsing AW, Grubb RL 3rd, Boeing H, Vineis P, Clavel-Chapelon F, Palli D, Tumino R, Krogh V, Panico S, Duell EJ, Quirós JR, Sanchez MJ, Navarro C, Ardanaz E, Dorronsoro M, Khaw KT, Allen NE, Bueno-de-Mesquita HB, Peeters PH, Trichopoulos D, Linseisen J, Ljungberg B, Overvad K, Tjønneland A, Romieu I, Riboli E, Mukeria A, Shangina O, Stevens VL, Thun MJ, Diver WR, Gapstur SM, Pharoah PD, Easton DF, Albanes D, Weinstein SJ, Virtamo J, Vatten L, Hveem K, Njølstad I, Tell GS, Stoltenberg C, Kumar R, Koppova K, Cussenot O, Benhamou S, Oosterwijk E, Vermeulen SH, Aben KK, van der Marel SL, Ye Y, Wood CG, Pu X, Mazur AM, Boulygina ES, Chekanov NN, Foglio M, Lechner D, Gut I, Heath S, Blanche H, Hutchinson A, Thomas G, Wang Z, Yeager M, Fraumeni JF Jr, Skryabin KG, McKay JD, Rothman N, Chanock SJ, Lathrop M, and Brennan P
- Subjects
- Case-Control Studies, Genome, Human, Humans, Polymorphism, Single Nucleotide, Risk Factors, Carcinoma, Renal Cell genetics, Chromosomes, Human, Pair 11 genetics, Chromosomes, Human, Pair 2 genetics, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Kidney Neoplasms genetics
- Abstract
We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r² = 0.99 in controls), rs11894252 (P = 1.8 × 10⁻⁸) and rs7579899 (P = 2.3 × 10⁻⁹), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 × 10⁻¹⁴). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 × 10⁻⁸). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.
- Published
- 2011
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46. A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.
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Rothman N, Garcia-Closas M, Chatterjee N, Malats N, Wu X, Figueroa JD, Real FX, Van Den Berg D, Matullo G, Baris D, Thun M, Kiemeney LA, Vineis P, De Vivo I, Albanes D, Purdue MP, Rafnar T, Hildebrandt MA, Kiltie AE, Cussenot O, Golka K, Kumar R, Taylor JA, Mayordomo JI, Jacobs KB, Kogevinas M, Hutchinson A, Wang Z, Fu YP, Prokunina-Olsson L, Burdett L, Yeager M, Wheeler W, Tardón A, Serra C, Carrato A, García-Closas R, Lloreta J, Johnson A, Schwenn M, Karagas MR, Schned A, Andriole G Jr, Grubb R 3rd, Black A, Jacobs EJ, Diver WR, Gapstur SM, Weinstein SJ, Virtamo J, Cortessis VK, Gago-Dominguez M, Pike MC, Stern MC, Yuan JM, Hunter DJ, McGrath M, Dinney CP, Czerniak B, Chen M, Yang H, Vermeulen SH, Aben KK, Witjes JA, Makkinje RR, Sulem P, Besenbacher S, Stefansson K, Riboli E, Brennan P, Panico S, Navarro C, Allen NE, Bueno-de-Mesquita HB, Trichopoulos D, Caporaso N, Landi MT, Canzian F, Ljungberg B, Tjonneland A, Clavel-Chapelon F, Bishop DT, Teo MT, Knowles MA, Guarrera S, Polidoro S, Ricceri F, Sacerdote C, Allione A, Cancel-Tassin G, Selinski S, Hengstler JG, Dietrich H, Fletcher T, Rudnai P, Gurzau E, Koppova K, Bolick SC, Godfrey A, Xu Z, Sanz-Velez JI, D García-Prats M, Sanchez M, Valdivia G, Porru S, Benhamou S, Hoover RN, Fraumeni JF Jr, Silverman DT, and Chanock SJ
- Subjects
- Arylamine N-Acetyltransferase genetics, Arylamine N-Acetyltransferase metabolism, Chromosome Mapping methods, Europe epidemiology, Family, Female, Humans, Incidence, Male, Neoplasm Staging, Risk Assessment, Risk Factors, Sex Characteristics, Smoking adverse effects, Spain epidemiology, United States epidemiology, Urinary Bladder Neoplasms epidemiology, Urinary Bladder Neoplasms pathology, Chromosomes, Human, Pair 18 genetics, Chromosomes, Human, Pair 2 genetics, Chromosomes, Human, Pair 22 genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Urinary Bladder Neoplasms genetics
- Abstract
We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.
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- 2010
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47. Lifetime exposure to arsenic in residential drinking water in Central Europe.
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Hough RL, Fletcher T, Leonardi GS, Goessler W, Gnagnarella P, Clemens F, Gurzau E, Koppova K, Rudnai P, Kumar R, and Vahter M
- Subjects
- Adult, Aged, Arsenic Poisoning complications, Arsenic Poisoning epidemiology, Case-Control Studies, Environmental Exposure adverse effects, Europe, Female, Health Behavior, Humans, Male, Middle Aged, Neoplasms etiology, Socioeconomic Factors, Water Pollutants, Chemical poisoning, Water Pollution, Chemical adverse effects, Arsenic analysis, Environmental Exposure analysis, Water Pollutants, Chemical analysis, Water Pollution, Chemical analysis, Water Supply analysis
- Abstract
Objective: Methods and results are presented for an arsenic exposure assessment integral to an epidemiological case-control study of arsenic and cancer-the European Commission funded ASHRAM (Arsenic Health Risk Assessment and Molecular Epidemiology) study carried out in some counties of Hungary, Romania and Slovakia., Methods: The exposure history of each participant (N = 1,392) was constructed by taking into account how much water they consumed (as water, in drinks and in food), sources of drinking water in their various residences over their lifetime, and the concentrations of arsenic in their various water supplies measured by Hydride Generation-Atomic Absorption Spectrometry (HG-AAS). Concentrations of arsenic in previous water supplies were either derived from contemporary analyses of the same source, or from routine historical data from measurements performed by the authorities in each country. Using this approach, 80% of the recorded lifetime residential history was matched to an arsenic concentration. Seven indices of current, life time, and peak exposure were calculated., Results: The exposure indices were all log-normally distributed and the mean and median lifetime average concentrations were in Hungary 14.7 and 13.3 microg l(-1), Romania 3.8 and 0.7 microg l(-1) and in Slovakia 1.9 and 0.8 microg l(-1), respectively. Overall 25% of the population had average concentrations over 10 microg l(-1) and 8% with exposure over 50 microg l(-1)., Conclusions: Careful assessment of arsenic in drinking water supplies (both current and previous) enabled the majority of study participants' cumulative lifetime of potential exposure to arsenic in residential water to be characterised.
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- 2010
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48. A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.
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Kiemeney LA, Sulem P, Besenbacher S, Vermeulen SH, Sigurdsson A, Thorleifsson G, Gudbjartsson DF, Stacey SN, Gudmundsson J, Zanon C, Kostic J, Masson G, Bjarnason H, Palsson ST, Skarphedinsson OB, Gudjonsson SA, Witjes JA, Grotenhuis AJ, Verhaegh GW, Bishop DT, Sak SC, Choudhury A, Elliott F, Barrett JH, Hurst CD, de Verdier PJ, Ryk C, Rudnai P, Gurzau E, Koppova K, Vineis P, Polidoro S, Guarrera S, Sacerdote C, Campagna M, Placidi D, Arici C, Zeegers MP, Kellen E, Gutierrez BS, Sanz-Velez JI, Sanchez-Zalabardo M, Valdivia G, Garcia-Prats MD, Hengstler JG, Blaszkewicz M, Dietrich H, Ophoff RA, van den Berg LH, Alexiusdottir K, Kristjansson K, Geirsson G, Nikulasson S, Petursdottir V, Kong A, Thorgeirsson T, Mungan NA, Lindblom A, van Es MA, Porru S, Buntinx F, Golka K, Mayordomo JI, Kumar R, Matullo G, Steineck G, Kiltie AE, Aben KK, Jonsson E, Thorsteinsdottir U, Knowles MA, Rafnar T, and Stefansson K
- Subjects
- Alleles, Disease-Free Survival, Europe, Female, Genotype, Humans, Male, Models, Genetic, Mutation, Receptor, Fibroblast Growth Factor, Type 3 genetics, Recurrence, Risk, Smoking, Chromosomes, Human, Pair 4, Genetic Predisposition to Disease, Genetic Variation, Urinary Bladder Neoplasms genetics
- Abstract
Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
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- 2010
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49. Polymorphisms in DNA repair genes, smoking, and bladder cancer risk: findings from the international consortium of bladder cancer.
- Author
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Stern MC, Lin J, Figueroa JD, Kelsey KT, Kiltie AE, Yuan JM, Matullo G, Fletcher T, Benhamou S, Taylor JA, Placidi D, Zhang ZF, Steineck G, Rothman N, Kogevinas M, Silverman D, Malats N, Chanock S, Wu X, Karagas MR, Andrew AS, Nelson HH, Bishop DT, Sak SC, Choudhury A, Barrett JH, Elliot F, Corral R, Joshi AD, Gago-Dominguez M, Cortessis VK, Xiang YB, Gao YT, Vineis P, Sacerdote C, Guarrera S, Polidoro S, Allione A, Gurzau E, Koppova K, Kumar R, Rudnai P, Porru S, Carta A, Campagna M, Arici C, Park SS, and Garcia-Closas M
- Subjects
- DNA-Binding Proteins genetics, Female, Humans, Male, Racial Groups, Risk, Risk Factors, Urinary Bladder Neoplasms epidemiology, Urinary Bladder Neoplasms pathology, Xeroderma Pigmentosum Group D Protein genetics, DNA Repair genetics, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Smoking genetics, Urinary Bladder Neoplasms genetics
- Abstract
Tobacco smoking is the most important and well-established bladder cancer risk factor and a rich source of chemical carcinogens and reactive oxygen species that can induce damage to DNA in urothelial cells. Therefore, common variation in DNA repair genes might modify bladder cancer risk. In this study, we present results from meta-analyses and pooled analyses conducted as part of the International Consortium of Bladder Cancer. We included data on 10 single nucleotide polymorphisms corresponding to seven DNA repair genes from 13 studies. Pooled analyses and meta-analyses included 5,282 cases and 5,954 controls of non-Latino white origin. We found evidence for weak but consistent associations with ERCC2 D312N [rs1799793; per-allele odds ratio (OR), 1.10; 95% confidence interval (95% CI), 1.01-1.19; P = 0.021], NBN E185Q (rs1805794; per-allele OR, 1.09; 95% CI, 1.01-1.18; P = 0.028), and XPC A499V (rs2228000; per-allele OR, 1.10; 95% CI, 1.00-1.21; P = 0.044). The association with NBN E185Q was limited to ever smokers (interaction P = 0.002) and was strongest for the highest levels of smoking dose and smoking duration. Overall, our study provides the strongest evidence to date for a role of common variants in DNA repair genes in bladder carcinogenesis.
- Published
- 2009
- Full Text
- View/download PDF
50. New common variants affecting susceptibility to basal cell carcinoma.
- Author
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Stacey SN, Sulem P, Masson G, Gudjonsson SA, Thorleifsson G, Jakobsdottir M, Sigurdsson A, Gudbjartsson DF, Sigurgeirsson B, Benediktsdottir KR, Thorisdottir K, Ragnarsson R, Scherer D, Hemminki K, Rudnai P, Gurzau E, Koppova K, Botella-Estrada R, Soriano V, Juberias P, Saez B, Gilaberte Y, Fuentelsaz V, Corredera C, Grasa M, Höiom V, Lindblom A, Bonenkamp JJ, van Rossum MM, Aben KK, de Vries E, Santinami M, Di Mauro MG, Maurichi A, Wendt J, Hochleitner P, Pehamberger H, Gudmundsson J, Magnusdottir DN, Gretarsdottir S, Holm H, Steinthorsdottir V, Frigge ML, Blondal T, Saemundsdottir J, Bjarnason H, Kristjansson K, Bjornsdottir G, Okamoto I, Rivoltini L, Rodolfo M, Kiemeney LA, Hansson J, Nagore E, Mayordomo JI, Kumar R, Karagas MR, Nelson HH, Gulcher JR, Rafnar T, Thorsteinsdottir U, Olafsson JH, Kong A, and Stefansson K
- Subjects
- Carcinoma, Basal Cell complications, Carcinoma, Squamous Cell genetics, Chromosomes, Human, Pair 7 genetics, Chromosomes, Human, Pair 9 genetics, Coronary Artery Disease complications, Coronary Artery Disease genetics, Genome-Wide Association Study, Humans, Keratin-5 genetics, Linkage Disequilibrium genetics, Melanoma pathology, Membrane Proteins genetics, Molecular Sequence Data, Neoplasm Proteins genetics, Skin Neoplasms complications, Carcinoma, Basal Cell genetics, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide genetics, Skin Neoplasms genetics
- Abstract
In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 x 10(-9)). A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 x 10(-9)), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 x 10(-10)). The effect of rs157935[T] is dependent on the parental origin of the risk allele. None of these variants were found to be associated with melanoma or fair-pigmentation traits. A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. Finally, we report conclusive evidence that rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects against melanoma.
- Published
- 2009
- Full Text
- View/download PDF
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