Search

Your search keyword '"Hartge P"' showing total 1,028 results
Start Over Author "Hartge P"
1,028 results on '"Hartge P"'

58. Body mass index, effect modifiers, and risk of pancreatic cancer: a pooled study of seven prospective cohorts

Author

Jiao, Li, Berrington de Gonzalez, Amy, Hartge, Patricia, Pfeiffer, Ruth M., Park, Yikyung, Freedman, D. Michal, Gail, Mitchell H., Alavanja, Michael C. R., Albanes, Demetrius, Beane Freeman, Laura E., Chow, Wong-Ho, Huang, Wen-Yi, Hayes, Richard B., Hoppin, Jane A., Ji, Bu-tian, Leitzmann, Michael F., Linet, Martha S., Meinhold, Cari L., Schairer, Catherine, Schatzkin, Arthur, Virtamo, Jarmo, Weinstein, Stephanie J., Zheng, Wei, and Stolzenberg-Solomon, Rachael Z.

Published
2010
Full Text
View/download PDF

67. Smoking modifies pancreatic cancer risk loci on 2q21.3

Author

Mocci, E. Kundu, P. Wheeler, W. Arslan, A.A. Beane-Freeman, L.E. Bracci, P.M. Brennan, P. Canzian, F. Du, M. Gallinger, S. Giles, G.G. Goodman, P.J. Kooperberg, C. Le Marchand, L. Neale, R.E. Shu, X.-O. Visvanathan, K. White, E. Zheng, W. Albanes, D. Andreotti, G. Babic, A. Bamlet, W.R. Berndt, S.I. Blackford, A.L. Bueno-De-Mesquita, B. Buring, J.E. Campa, D. Chanock, S.J. Childs, E.J. Duell, E.J. Fuchs, C.S. Gaziano, J.M. Giovannucci, E.L. Goggins, M.G. Hartge, P. Hassan, M.M. Holly, E.A. Hoover, R.N. Hung, R.J. Kurtz, R.C. Lee, I.-M. Malats, N. Milne, R.L. Ng, K. Oberg, A.L. Panico, S. Peters, U. Porta, M. Rabe, K.G. Riboli, E. Rothman, N. Scelo, G. Sesso, H.D. Silverman, D.T. Stevens, V.L. Strobel, O. Thompson, I.M., Jr. Tjonneland, A. Trichopoulou, A. van Den Eeden, S.K. Wactawski-Wende, J. Wentzensen, N. Wilkens, L.R. Yu, H. Yuan, F. Zeleniuch-Jacquotte, A. Amundadottir, L.T. Li, D. Jacobs, E.J. Petersen, G.M. Wolpin, B.M. Risch, H.A. Kraft, P. Chatterjee, N. Klein, A.P. Stolzenberg-Solomon, R. and Mocci, E. Kundu, P. Wheeler, W. Arslan, A.A. Beane-Freeman, L.E. Bracci, P.M. Brennan, P. Canzian, F. Du, M. Gallinger, S. Giles, G.G. Goodman, P.J. Kooperberg, C. Le Marchand, L. Neale, R.E. Shu, X.-O. Visvanathan, K. White, E. Zheng, W. Albanes, D. Andreotti, G. Babic, A. Bamlet, W.R. Berndt, S.I. Blackford, A.L. Bueno-De-Mesquita, B. Buring, J.E. Campa, D. Chanock, S.J. Childs, E.J. Duell, E.J. Fuchs, C.S. Gaziano, J.M. Giovannucci, E.L. Goggins, M.G. Hartge, P. Hassan, M.M. Holly, E.A. Hoover, R.N. Hung, R.J. Kurtz, R.C. Lee, I.-M. Malats, N. Milne, R.L. Ng, K. Oberg, A.L. Panico, S. Peters, U. Porta, M. Rabe, K.G. Riboli, E. Rothman, N. Scelo, G. Sesso, H.D. Silverman, D.T. Stevens, V.L. Strobel, O. Thompson, I.M., Jr. Tjonneland, A. Trichopoulou, A. van Den Eeden, S.K. Wactawski-Wende, J. Wentzensen, N. Wilkens, L.R. Yu, H. Yuan, F. Zeleniuch-Jacquotte, A. Amundadottir, L.T. Li, D. Jacobs, E.J. Petersen, G.M. Wolpin, B.M. Risch, H.A. Kraft, P. Chatterjee, N. Klein, A.P. Stolzenberg-Solomon, R.

Abstract

Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P < 5 10-8 was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region that included 45 significantly associated SNPs, was rs1818613 [per allele OR in never smokers 0.87, 95% confidence interval (CI), 0.82-0.93; former smokers 1.00, 95% CI, 0.91-1.07; current smokers 1.25, 95% CI 1.12-1.40, Pinteraction ¼ 3.08 10-9). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high linkage disequilibrium with rs1818613 (r2 ¼ 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings. © 2021 American Association for Cancer Research.

Published
2021

68. Genome-wide genediabetes and geneobesity interaction scan in 8,255 cases and 11,900 controls from panscan and PanC4 consortia.

Author

Campa D., Goodman P.J., Kooperberg C., Le Marchand L., Neale R.E., Shu X.-O., Visvanathan K., White E., Zheng W., Albanes D., Andreotti G., Babic A., Bamlet W.R., Berndt S.I., Blackford A., Bueno-De-Mesquita B., Buring J.E., Chanock S.J., Childs E., Duell E.J., Fuchs C., Michael Gaziano J., Goggins M., Hartge P., Hassam M.H., Holly E.A., Hoover R.N., Hung R.J., Kurtz R.C., Lee I.-M., Malats N., Milne R.L., Ng K., Oberg A.L., Orlow I., Peters U., Porta M., Rabe K.G., Rothman N., Scelo G., Sesso H.D., Silverman D.T., Thompson I.M., Tjonneland A., Trichopoulou A., Wactawski-Wende J., Wentzensen N., Wilkens L.R., Yu H., Zeleniuch-Jacquotte A., Amundadottir L.T., Jacobs E.J., Petersen G.M., Wolpin B.M., Risch H.A., Chatterjee N., Klein A.P., Li D., Kraft P., Wei P., Tang H., Jiang L., Stolzenberg-Solomon R.Z., Arslan A.A., Beane Freeman L.E., Bracci P.M., Brennan P., Canzian F., Du M., Gallinger S., Giles G.G., Campa D., Goodman P.J., Kooperberg C., Le Marchand L., Neale R.E., Shu X.-O., Visvanathan K., White E., Zheng W., Albanes D., Andreotti G., Babic A., Bamlet W.R., Berndt S.I., Blackford A., Bueno-De-Mesquita B., Buring J.E., Chanock S.J., Childs E., Duell E.J., Fuchs C., Michael Gaziano J., Goggins M., Hartge P., Hassam M.H., Holly E.A., Hoover R.N., Hung R.J., Kurtz R.C., Lee I.-M., Malats N., Milne R.L., Ng K., Oberg A.L., Orlow I., Peters U., Porta M., Rabe K.G., Rothman N., Scelo G., Sesso H.D., Silverman D.T., Thompson I.M., Tjonneland A., Trichopoulou A., Wactawski-Wende J., Wentzensen N., Wilkens L.R., Yu H., Zeleniuch-Jacquotte A., Amundadottir L.T., Jacobs E.J., Petersen G.M., Wolpin B.M., Risch H.A., Chatterjee N., Klein A.P., Li D., Kraft P., Wei P., Tang H., Jiang L., Stolzenberg-Solomon R.Z., Arslan A.A., Beane Freeman L.E., Bracci P.M., Brennan P., Canzian F., Du M., Gallinger S., and Giles G.G.

Abstract

Background: Obesity and diabetes are major modifiable risk factors for pancreatic cancer. Interactions between genetic variants and diabetes/obesity have not previously been comprehensively investigated in pancreatic cancer at the genome-wide level. Method(s): We conducted a gene-environment interaction (GxE) analysis including 8,255 cases and 11,900 controls from four pancreatic cancer genome-wide association study (GWAS) datasets (Pancreatic Cancer Cohort Consortium I-III and Pancreatic Cancer Case Control Consortium). Obesity (body mass index >=30 kg/m2) and diabetes (duration >=3 years) were the environmental variables of interest. Approximately 870,000 SNPs (minor allele frequency >=0.005, genotyped in at least one dataset) were analyzed. Case-control (CC), case-only (CO), and joint-effect test methods were used for SNP-level GxE analysis. As a complementary approach, gene-based GxE analysis was also performed. Age, sex, study site, and principal components accounting for population substructure were included as covariates. Meta-analysis was applied to combine individual GWAS summary statistics. Result(s): No genome-wide significant interactions (departures from a log-additive odds model) with diabetes or obesity were detected at the SNP level by the CC or CO approaches. The joint-effect test detected numerous genome-wide significant GxE signals in the GWAS main effects top hit regions, but the significance diminished after adjusting for the GWAS top hits. In the gene-based analysis, a significant interaction of diabetes with variants in the FAM63A (family with sequence similarity 63 member A) gene (significance threshold P < 1.25 106) was observed in the meta-analysis (PGxE 1/4 1.2 106, PJoint 1/4 4.2 107). Conclusion(s): This analysis did not find significant GxE interactions at the SNP level but found one significant interaction with diabetes at the gene level. A larger sample size might unveil additional genetic factors via GxE scans. Impact: This study may

Published
2021

69. Smoking modifies pancreatic cancer risk loci on 2q21.3.

Author

Mocci E., Kundu P., Wheeler W., Arslan A.A., Beane-Freeman L.E., Bracci P.M., Brennan P., Canzian F., Du M., Gallinger S., Giles G.G., Goodman P.J., Kooperberg C., Le Marchand L., Neale R.E., Shu X.-O., Visvanathan K., White E., Zheng W., Albanes D., Andreotti G., Babic A., Bamlet W.R., Berndt S.I., Blackford A.L., Bueno-De-Mesquita B., Buring J.E., Campa D., Chanock S.J., Childs E.J., Duell E.J., Fuchs C.S., Gaziano J.M., Giovannucci E.L., Goggins M.G., Hartge P., Hassan M.M., Holly E.A., Hoover R.N., Hung R.J., Kurtz R.C., Lee I.-M., Malats N., Milne R.L., Ng K., Oberg A.L., Panico S., Peters U., Porta M., Rabe K.G., Riboli E., Rothman N., Scelo G., Sesso H.D., Silverman D.T., Stevens V.L., Strobel O., Thompson I.M., Tjonneland A., Trichopoulou A., van Den Eeden S.K., Wactawski-Wende J., Wentzensen N., Wilkens L.R., Yu H., Yuan F., Zeleniuch-Jacquotte A., Amundadottir L.T., Li D., Jacobs E.J., Petersen G.M., Wolpin B.M., Risch H.A., Kraft P., Chatterjee N., Klein A.P., Stolzenberg-Solomon R., Mocci E., Kundu P., Wheeler W., Arslan A.A., Beane-Freeman L.E., Bracci P.M., Brennan P., Canzian F., Du M., Gallinger S., Giles G.G., Goodman P.J., Kooperberg C., Le Marchand L., Neale R.E., Shu X.-O., Visvanathan K., White E., Zheng W., Albanes D., Andreotti G., Babic A., Bamlet W.R., Berndt S.I., Blackford A.L., Bueno-De-Mesquita B., Buring J.E., Campa D., Chanock S.J., Childs E.J., Duell E.J., Fuchs C.S., Gaziano J.M., Giovannucci E.L., Goggins M.G., Hartge P., Hassan M.M., Holly E.A., Hoover R.N., Hung R.J., Kurtz R.C., Lee I.-M., Malats N., Milne R.L., Ng K., Oberg A.L., Panico S., Peters U., Porta M., Rabe K.G., Riboli E., Rothman N., Scelo G., Sesso H.D., Silverman D.T., Stevens V.L., Strobel O., Thompson I.M., Tjonneland A., Trichopoulou A., van Den Eeden S.K., Wactawski-Wende J., Wentzensen N., Wilkens L.R., Yu H., Yuan F., Zeleniuch-Jacquotte A., Amundadottir L.T., Li D., Jacobs E.J., Petersen G.M., Wolpin B.M., Risch H.A., Kraft P., Chatterjee N., Klein A.P., and Stolzenberg-Solomon R.

Abstract

Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P < 5 10-8 was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region that included 45 significantly associated SNPs, was rs1818613 [per allele OR in never smokers 0.87, 95% confidence interval (CI), 0.82-0.93; former smokers 1.00, 95% CI, 0.91-1.07; current smokers 1.25, 95% CI 1.12-1.40, Pinteraction 1/4 3.08 10-9). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high linkage disequilibrium with rs1818613 (r2 1/4 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings.Copyright © 2021 American Association for Cancer Research.

Published
2021

70. Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a pathway analysis of genome-wide association studies.

Author

Julian-Serrano S., Yuan F., Wheeler W., Benyamin B., Machiela M.J., Arslan A.A., Beane-Freeman L.E., Bracci P.M., Duell E.J., Du M., Gallinger S., Giles G.G., Goodman P.J., Kooperberg C., Marchand L.L., Neale R.E., Shu X.-O., Van Den Eeden S.K., Visvanathan K., Zheng W., Albanes D., Andreotti G., Ardanaz E., Babic A., Berndt S.I., Brais L.K., Brennan P., Bueno-de-Mesquita B., Buring J.E., Chanock S.J., Childs E.J., Chung C.C., Fabianova E., Foretova L., Fuchs C.S., Gaziano J.M., Gentiluomo M., Giovannucci E.L., Goggins M.G., Hackert T., Hartge P., Hassan M.M., Holcatova I., Holly E.A., Hung R.I., Janout V., Kurtz R.C., Lee I.-M., Malats N., McKean D., Milne R.L., Newton C.C., Oberg A.L., Perdomo S., Peters U., Porta M., Rothman N., Schulze M.B., Sesso H.D., Silverman D.T., Thompson I.M., Wactawski-Wende J., Weiderpass E., Wenstzensen N., White E., Wilkens L.R., Yu H., Zeleniuch-Jacquotte A., Zhong J., Kraft P., Li D., Campbell P.T., Petersen G.M., Wolpin B.M., Risch H.A., Amundadottir L.T., Klein A.P., Yu K., Stolzenberg-Solomon R.Z., Julian-Serrano S., Yuan F., Wheeler W., Benyamin B., Machiela M.J., Arslan A.A., Beane-Freeman L.E., Bracci P.M., Duell E.J., Du M., Gallinger S., Giles G.G., Goodman P.J., Kooperberg C., Marchand L.L., Neale R.E., Shu X.-O., Van Den Eeden S.K., Visvanathan K., Zheng W., Albanes D., Andreotti G., Ardanaz E., Babic A., Berndt S.I., Brais L.K., Brennan P., Bueno-de-Mesquita B., Buring J.E., Chanock S.J., Childs E.J., Chung C.C., Fabianova E., Foretova L., Fuchs C.S., Gaziano J.M., Gentiluomo M., Giovannucci E.L., Goggins M.G., Hackert T., Hartge P., Hassan M.M., Holcatova I., Holly E.A., Hung R.I., Janout V., Kurtz R.C., Lee I.-M., Malats N., McKean D., Milne R.L., Newton C.C., Oberg A.L., Perdomo S., Peters U., Porta M., Rothman N., Schulze M.B., Sesso H.D., Silverman D.T., Thompson I.M., Wactawski-Wende J., Weiderpass E., Wenstzensen N., White E., Wilkens L.R., Yu H., Zeleniuch-Jacquotte A., Zhong J., Kraft P., Li D., Campbell P.T., Petersen G.M., Wolpin B.M., Risch H.A., Amundadottir L.T., Klein A.P., Yu K., and Stolzenberg-Solomon R.Z.

Abstract

BACKGROUND: Epidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis. OBJECTIVE(S): The objective of this study was to determine whether common genetic variation in the hepcidin-regulating iron metabolism pathway is associated with PDAC. METHOD(S): We conducted a pathway analysis of the hepcidin-regulating genes using single nucleotide polymorphism (SNP) summary statistics generated from 4 genome-wide association studies in 2 large consortium studies using the summary data-based adaptive rank truncated product method. Our population consisted of 9253 PDAC cases and 12,525 controls of European descent. Our analysis included 11 hepcidin-regulating genes [bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 6 (BMP6), ferritin heavy chain 1 (FTH1), ferritin light chain (FTL), hepcidin (HAMP), homeostatic iron regulator (HFE), hemojuvelin (HJV), nuclear factor erythroid 2-related factor 2 (NRF2), ferroportin 1 (SLC40A1), transferrin receptor 1 (TFR1), and transferrin receptor 2 (TFR2)] and their surrounding genomic regions (+/-20 kb) for a total of 412 SNPs. RESULT(S): The hepcidin-regulating gene pathway was significantly associated with PDAC (P = 0.002), with the HJV, TFR2, TFR1, BMP6, and HAMP genes contributing the most to the association. CONCLUSION(S): Our results support that genetic susceptibility related to the hepcidin-regulating gene pathway is associated with PDAC risk and suggest a potential role of iron metabolism in pancreatic carcinogenesis. Further studies are needed to evaluate effect modification by intake of iron-rich foods on this association.Copyright Published by Oxford University Press on behalf of the American Society for Nutrition 2021.

Published
2021

71. Genome-wide association study data reveal genetic susceptibility to chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma risk.

Author

Wang X., Yuan F., Hung R.J., Walsh N., Zhang H., Platz E.A., Wheeler W., Song L., Arslan A.A., Beane Freeman L.E., Bracci P., Canzian F., Du M., Wilkens L.R., Yu H., Zeleniuch-Jacquotte A., Shi J., Duell E.J., Amundadottir L.T., Li D., Petersen G.M., Wolpin B.M., Risch H.A., Yu K., Klein A.P., Stolzenberg-Solomon R., Gallinger S., Giles G.G., Goodman P.J., Kooperberg C., Le Marchand L., Neale R.E., Rosendahl J., Scelo G., Shu X.-O., Visvanathan K., White E., Zheng W., Albanes D., Amiano P., Andreotti G., Babic A., Bamlet W.R., Berndt S.I., Brennan P., Bueno-De-Mesquita B., Buring J.E., Campbell P.T., Chanock S.J., Fuchs C.S., Michael Gaziano J., Goggins M.G., Hackert T., Hartge P., Hassan M.M., Holly E.A., Hoover R.N., Katzke V., Kirsten H., Kurtz R.C., Lee I.-M., Malats N., Milne R.L., Murphy N., Ng K., Oberg A.L., Porta M., Rabe K.G., Real F.X., Rothman N., Sesso H.D., Silverman D.T., Thompson I.M., Wactawski-Wende J., Wentzensen N., Wang X., Yuan F., Hung R.J., Walsh N., Zhang H., Platz E.A., Wheeler W., Song L., Arslan A.A., Beane Freeman L.E., Bracci P., Canzian F., Du M., Wilkens L.R., Yu H., Zeleniuch-Jacquotte A., Shi J., Duell E.J., Amundadottir L.T., Li D., Petersen G.M., Wolpin B.M., Risch H.A., Yu K., Klein A.P., Stolzenberg-Solomon R., Gallinger S., Giles G.G., Goodman P.J., Kooperberg C., Le Marchand L., Neale R.E., Rosendahl J., Scelo G., Shu X.-O., Visvanathan K., White E., Zheng W., Albanes D., Amiano P., Andreotti G., Babic A., Bamlet W.R., Berndt S.I., Brennan P., Bueno-De-Mesquita B., Buring J.E., Campbell P.T., Chanock S.J., Fuchs C.S., Michael Gaziano J., Goggins M.G., Hackert T., Hartge P., Hassan M.M., Holly E.A., Hoover R.N., Katzke V., Kirsten H., Kurtz R.C., Lee I.-M., Malats N., Milne R.L., Murphy N., Ng K., Oberg A.L., Porta M., Rabe K.G., Real F.X., Rothman N., Sesso H.D., Silverman D.T., Thompson I.M., Wactawski-Wende J., and Wentzensen N.

Abstract

Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (+500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 x 10-6, respectively). After excluding the 20 PDAC susceptibility regions (+500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P 1/4 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P 1/4 0.22) and primary sclerosing cholangitis (P 1/4 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC.Copyright © 2020 American Association for Cancer Research.

Published
2021

72. A transcriptome-wide association study identifies novel candidate susceptibility genes for pancreatic cancer.

Author

Hasan M., Zhang T., Xiao W., Albanes D., Andreotti G., Arslan A.A., Babic A., Bamlet W.R., Beane-Freeman L., Berndt S., Borgida A., Bracci P.M., Brais L., Brennan P., Bueno-De-Mesquita B., Buring J., Canzian F., Childs E.J., Cotterchio M., Du M., Duell E.J., Fuchs C., Gallinger S., Michael Gaziano J., Giles G.G., Giovannucci E., Goggins M., Goodman G.E., Goodman P.J., Haiman C., Hartge P., Helzlsouer K.J., Holly E.A., Klein E.A., Kogevinas M., Kurtz R.J., LeMarchand L., Malats N., Mannisto S., Milne R., Neale R.E., Ng K., Obazee O., Oberg A.L., Orlow I., Patel A.V., Peters U., Porta M., Rothman N., Scelo G., Sesso H.D., Severi G., Sieri S., Silverman D., Sund M., Tjonneland A., Thornquist M.D., Tobias G.S., Trichopoulou A., van Den Eeden S.K., Visvanathan K., Wactawski-Wende J., Wentzensen N., White E., Yu H., Yuan C., Zeleniuch-Jacquotte A., Hoover R., Brown K., Kooperberg C., Risch H.A., Jacobs E.J., Li D., Yu K., Shu X.-O., Chanock S.J., Wolpin B.M., Stolzenberg-Solomon R.Z., Chatterjee N., Klein A.P., Smith J.P., Kraft P., Shi J., Petersen G.M., Zheng W., Amundadottir L.T., Zhong J., Jermusyk A., Wu L., Hoskins J.W., Collins I., Mocci E., Zhang M., Song L., Chung C.C., Hasan M., Zhang T., Xiao W., Albanes D., Andreotti G., Arslan A.A., Babic A., Bamlet W.R., Beane-Freeman L., Berndt S., Borgida A., Bracci P.M., Brais L., Brennan P., Bueno-De-Mesquita B., Buring J., Canzian F., Childs E.J., Cotterchio M., Du M., Duell E.J., Fuchs C., Gallinger S., Michael Gaziano J., Giles G.G., Giovannucci E., Goggins M., Goodman G.E., Goodman P.J., Haiman C., Hartge P., Helzlsouer K.J., Holly E.A., Klein E.A., Kogevinas M., Kurtz R.J., LeMarchand L., Malats N., Mannisto S., Milne R., Neale R.E., Ng K., Obazee O., Oberg A.L., Orlow I., Patel A.V., Peters U., Porta M., Rothman N., Scelo G., Sesso H.D., Severi G., Sieri S., Silverman D., Sund M., Tjonneland A., Thornquist M.D., Tobias G.S., Trichopoulou A., van Den Eeden S.K., Visvanathan K., Wactawski-Wende J., Wentzensen N., White E., Yu H., Yuan C., Zeleniuch-Jacquotte A., Hoover R., Brown K., Kooperberg C., Risch H.A., Jacobs E.J., Li D., Yu K., Shu X.-O., Chanock S.J., Wolpin B.M., Stolzenberg-Solomon R.Z., Chatterjee N., Klein A.P., Smith J.P., Kraft P., Shi J., Petersen G.M., Zheng W., Amundadottir L.T., Zhong J., Jermusyk A., Wu L., Hoskins J.W., Collins I., Mocci E., Zhang M., Song L., and Chung C.C.

Abstract

Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Method(s): To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples). Result(s): We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate <.05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22:RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusion(s): By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.Copyright © 2020 Oxford University Press. All rights reserved.

Published
2021

73. Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3

Author

Mocci, E, Kundu, P, Wheeler, W, Arslan, AA, Beane-Freeman, LE, Bracci, PM, Brennan, P, Canzian, F, Du, M, Gallinger, S, Giles, GG, Goodman, PJ, Kooperberg, C, Le Marchand, L, Neale, RE, Shu, X-O, Visvanathan, K, White, E, Zheng, W, Albanes, D, Andreotti, G, Babic, A, Bamlet, WR, Berndt, S, Blackford, AL, Bueno-de-Mesquita, B, Buring, JE, Campa, D, Chanock, SJ, Childs, EJ, Duell, EJ, Fuchs, CS, Gaziano, JM, Giovannucci, EL, Goggins, MG, Hartge, P, Hassan, MM, Holly, EA, Hoover, RN, Hung, RJ, Kurtz, RC, Lee, I-M, Malats, N, Milne, RL, Ng, K, Oberg, AL, Panico, S, Peters, U, Porta, M, Rabe, KG, Riboli, E, Rothman, N, Scelo, G, Sesso, HD, Silverman, DT, Stevens, VL, Strobel, O, Thompson, IM, Tjonneland, A, Trichopoulou, A, Van den Eeden, SK, Wactawski-Wende, J, Wentzensen, N, Wilkens, LR, Yu, H, Yuan, F, Zeleniuch-Jacquotte, A, Amundadottir, LT, Li, D, Jacobs, EJ, Petersen, GM, Wolpin, BM, Risch, HA, Kraft, P, Chatterjee, N, Klein, AP, Stolzenberg-Solomon, R, Mocci, E, Kundu, P, Wheeler, W, Arslan, AA, Beane-Freeman, LE, Bracci, PM, Brennan, P, Canzian, F, Du, M, Gallinger, S, Giles, GG, Goodman, PJ, Kooperberg, C, Le Marchand, L, Neale, RE, Shu, X-O, Visvanathan, K, White, E, Zheng, W, Albanes, D, Andreotti, G, Babic, A, Bamlet, WR, Berndt, S, Blackford, AL, Bueno-de-Mesquita, B, Buring, JE, Campa, D, Chanock, SJ, Childs, EJ, Duell, EJ, Fuchs, CS, Gaziano, JM, Giovannucci, EL, Goggins, MG, Hartge, P, Hassan, MM, Holly, EA, Hoover, RN, Hung, RJ, Kurtz, RC, Lee, I-M, Malats, N, Milne, RL, Ng, K, Oberg, AL, Panico, S, Peters, U, Porta, M, Rabe, KG, Riboli, E, Rothman, N, Scelo, G, Sesso, HD, Silverman, DT, Stevens, VL, Strobel, O, Thompson, IM, Tjonneland, A, Trichopoulou, A, Van den Eeden, SK, Wactawski-Wende, J, Wentzensen, N, Wilkens, LR, Yu, H, Yuan, F, Zeleniuch-Jacquotte, A, Amundadottir, LT, Li, D, Jacobs, EJ, Petersen, GM, Wolpin, BM, Risch, HA, Kraft, P, Chatterjee, N, Klein, AP, and Stolzenberg-Solomon, R

Abstract

Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P < 5 × 10-8 was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region that included 45 significantly associated SNPs, was rs1818613 [per allele OR in never smokers 0.87, 95% confidence interval (CI), 0.82-0.93; former smokers 1.00, 95% CI, 0.91-1.07; current smokers 1.25, 95% CI 1.12-1.40, P interaction = 3.08 × 10-9). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high linkage disequilibrium with rs1818613 (r 2 = 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings. SIGNIFICANCE: This large genome-wide interaction study identifies a susceptibility locus on 2q21.3 that significantly modified PDAC risk by smoking status, providing insight into smoking-associated PDAC, with implications for prevention.

Published
2021

74. Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a pathway analysis of genome-wide association studies

Author

Julian-Serrano, S, Yuan, F, Wheeler, W, Benyamin, B, Machiela, MJ, Arslan, AA, Beane-Freeman, LE, Bracci, PM, Duell, EJ, Du, M, Gallinger, S, Giles, GG, Goodman, PJ, Kooperberg, C, Le Marchand, L, Neale, RE, Shu, X-O, Van den Eeden, SK, Visvanathan, K, Zheng, W, Albanes, D, Andreotti, G, Ardanaz, E, Babic, A, Berndt, S, Brais, LK, Brennan, P, Bueno-de-Mesquita, B, Buring, JE, Chanock, SJ, Childs, EJ, Chung, CC, Fabianova, E, Foretova, L, Fuchs, CS, Gaziano, JM, Gentiluomo, M, Giovannucci, EL, Goggins, MG, Hackert, T, Hartge, P, Hassan, MM, Holcatova, I, Holly, EA, Hung, R, Janout, V, Kurtz, RC, Lee, I-M, Malats, N, McKean, D, Milne, RL, Newton, CC, Oberg, AL, Perdomo, S, Peters, U, Porta, M, Rothman, N, Schulze, MB, Sesso, HD, Silverman, DT, Thompson, IM, Wactawski-Wende, J, Weiderpass, E, Wenstzensen, N, White, E, Wilkens, LR, Yu, H, Zeleniuch-Jacquotte, A, Zhong, J, Kraft, P, Li, D, Campbell, PT, Petersen, GM, Wolpin, BM, Risch, HA, Amundadottir, LT, Klein, AP, Yu, K, Stolzenberg-Solomon, RZ, Julian-Serrano, S, Yuan, F, Wheeler, W, Benyamin, B, Machiela, MJ, Arslan, AA, Beane-Freeman, LE, Bracci, PM, Duell, EJ, Du, M, Gallinger, S, Giles, GG, Goodman, PJ, Kooperberg, C, Le Marchand, L, Neale, RE, Shu, X-O, Van den Eeden, SK, Visvanathan, K, Zheng, W, Albanes, D, Andreotti, G, Ardanaz, E, Babic, A, Berndt, S, Brais, LK, Brennan, P, Bueno-de-Mesquita, B, Buring, JE, Chanock, SJ, Childs, EJ, Chung, CC, Fabianova, E, Foretova, L, Fuchs, CS, Gaziano, JM, Gentiluomo, M, Giovannucci, EL, Goggins, MG, Hackert, T, Hartge, P, Hassan, MM, Holcatova, I, Holly, EA, Hung, R, Janout, V, Kurtz, RC, Lee, I-M, Malats, N, McKean, D, Milne, RL, Newton, CC, Oberg, AL, Perdomo, S, Peters, U, Porta, M, Rothman, N, Schulze, MB, Sesso, HD, Silverman, DT, Thompson, IM, Wactawski-Wende, J, Weiderpass, E, Wenstzensen, N, White, E, Wilkens, LR, Yu, H, Zeleniuch-Jacquotte, A, Zhong, J, Kraft, P, Li, D, Campbell, PT, Petersen, GM, Wolpin, BM, Risch, HA, Amundadottir, LT, Klein, AP, Yu, K, and Stolzenberg-Solomon, RZ

Abstract

BACKGROUND: Epidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis. OBJECTIVES: The objective of this study was to determine whether common genetic variation in the hepcidin-regulating iron metabolism pathway is associated with PDAC. METHODS: We conducted a pathway analysis of the hepcidin-regulating genes using single nucleotide polymorphism (SNP) summary statistics generated from 4 genome-wide association studies in 2 large consortium studies using the summary data-based adaptive rank truncated product method. Our population consisted of 9253 PDAC cases and 12,525 controls of European descent. Our analysis included 11 hepcidin-regulating genes [bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 6 (BMP6), ferritin heavy chain 1 (FTH1), ferritin light chain (FTL), hepcidin (HAMP), homeostatic iron regulator (HFE), hemojuvelin (HJV), nuclear factor erythroid 2-related factor 2 (NRF2), ferroportin 1 (SLC40A1), transferrin receptor 1 (TFR1), and transferrin receptor 2 (TFR2)] and their surrounding genomic regions (±20 kb) for a total of 412 SNPs. RESULTS: The hepcidin-regulating gene pathway was significantly associated with PDAC (P = 0.002), with the HJV, TFR2, TFR1, BMP6, and HAMP genes contributing the most to the association. CONCLUSIONS: Our results support that genetic susceptibility related to the hepcidin-regulating gene pathway is associated with PDAC risk and suggest a potential role of iron metabolism in pancreatic carcinogenesis. Further studies are needed to evaluate effect modification by intake of iron-rich foods on this association.

Published
2021

77. A Pooled Analysis of Bladder Cancer Case–Control Studies Evaluating Smoking in Men and Women

Author

Puente, Diana, Hartge, Patricia, Greiser, Eberhard, Cantor, Kenneth P., King, Will D., González, Carlos A., Cordier, Sylvaine, Vineis, Paolo, Lynge, Elsebeth, Chang-Claude, Jenny, Porru, Stefano, Tzonou, Anastasia, Jöckel, Karl-Heinz, Serra, Consol, Hours, Martine, Lynch, Charles F., Ranft, Ulrich, Wahrendorf, Jürgen, Silverman, Debra, Fernandez, Francisco, Boffetta, Paolo, and Kogevinas, Manolis

Published
2006
Full Text
View/download PDF

82. Genome-wide gene⇓diabetes and gene⇓obesity interaction scan in 8,255 cases and 11,900 controls from panscan and PanC4 consortia

Author

Tang, H. Jiang, L. Stolzenberg-Solomon, R.Z. Arslan, A.A. Beane Freeman, L.E. Bracci, P.M. Brennan, P. Canzian, F. Du, M. Gallinger, S. Giles, G.G. Goodman, P.J. Kooperberg, C. Le Marchand, L. Neale, R.E. Shu, X.-O. Visvanathan, K. White, E. Zheng, W. Albanes, D. Andreotti, G. Babic, A. Bamlet, W.R. Berndt, S.I. Blackford, A. Bueno-De-Mesquita, B. Buring, J.E. Campa, D. Chanock, S.J. Childs, E. Duell, E.J. Fuchs, C. Michael Gaziano, J. Goggins, M. Hartge, P. Hassam, M.H. Holly, E.A. Hoover, R.N. Hung, R.J. Kurtz, R.C. Lee, I.-M. Malats, N. Milne, R.L. Ng, K. Oberg, A.L. Orlow, I. Peters, U. Porta, M. Rabe, K.G. Rothman, N. Scelo, G. Sesso, H.D. Silverman, D.T. Thompson, I.M. Tjønneland, A. Trichopoulou, A. Wactawski-Wende, J. Wentzensen, N. Wilkens, L.R. Yu, H. Zeleniuch-Jacquotte, A. Amundadottir, L.T. Jacobs, E.J. Petersen, G.M. Wolpin, B.M. Risch, H.A. Chatterjee, N. Klein, A.P. Li, D. Kraft, P. Wei, P.

Abstract

Background: Obesity and diabetes are major modifiable risk factors for pancreatic cancer. Interactions between genetic variants and diabetes/obesity have not previously been comprehensively investigated in pancreatic cancer at the genome-wide level. Methods: We conducted a gene–environment interaction (GxE) analysis including 8,255 cases and 11,900 controls from four pancreatic cancer genome-wide association study (GWAS) datasets (Pancreatic Cancer Cohort Consortium I–III and Pancreatic Cancer Case Control Consortium). Obesity (body mass index ≥30 kg/m2) and diabetes (duration ≥3 years) were the environmental variables of interest. Approximately 870,000 SNPs (minor allele frequency ≥0.005, genotyped in at least one dataset) were analyzed. Case–control (CC), case-only (CO), and joint-effect test methods were used for SNP-level GxE analysis. As a complementary approach, gene-based GxE analysis was also performed. Age, sex, study site, and principal components accounting for population substructure were included as covariates. Meta-analysis was applied to combine individual GWAS summary statistics. Results: No genome-wide significant interactions (departures from a log-additive odds model) with diabetes or obesity were detected at the SNP level by the CC or CO approaches. The joint-effect test detected numerous genome-wide significant GxE signals in the GWAS main effects top hit regions, but the significance diminished after adjusting for the GWAS top hits. In the gene-based analysis, a significant interaction of diabetes with variants in the FAM63A (family with sequence similarity 63 member A) gene (significance threshold P < 1.25 106) was observed in the meta-analysis (PGxE ¼ 1.2 106, PJoint ¼ 4.2 107). Conclusions: This analysis did not find significant GxE interactions at the SNP level but found one significant interaction with diabetes at the gene level. A larger sample size might unveil additional genetic factors via GxE scans. Impact: This study may contribute to discovering the mechanism of diabetes-associated pancreatic cancer. © 2020 American Association for Cancer Research.

Published
2020

84. Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project.

Author

Shadyab A.H., Weiderpass E., Wolk A., Yang H.-I., Zheng W., McGlynn K.A., Campbell P.T., Koshiol J., Jackson S.S., Adami H.-O., Andreotti G., Beane-Freeman L.E., de Gonzalez A.B., Buring J.E., Fraser G.E., Freedman N.D., Gapstur S.M., Gierach G., Giles G.G., Grodstein F., Hartge P., Jenab M., Kirsh V., Knutsen S.F., Lan Q., Larsson S.C., Lee I.-M., Lee M.-H., Liao L.M., Milne R.L., Monroe K.R., Neuhouser M.L., O'Brien K.M., Petrick J.L., Purdue M.P., Rohan T.E., Sandin S., Sandler D.P., Sawada N., Simon T.G., Sinha R., Stolzenberg-Solomon R., Tsugane S., Shadyab A.H., Weiderpass E., Wolk A., Yang H.-I., Zheng W., McGlynn K.A., Campbell P.T., Koshiol J., Jackson S.S., Adami H.-O., Andreotti G., Beane-Freeman L.E., de Gonzalez A.B., Buring J.E., Fraser G.E., Freedman N.D., Gapstur S.M., Gierach G., Giles G.G., Grodstein F., Hartge P., Jenab M., Kirsh V., Knutsen S.F., Lan Q., Larsson S.C., Lee I.-M., Lee M.-H., Liao L.M., Milne R.L., Monroe K.R., Neuhouser M.L., O'Brien K.M., Petrick J.L., Purdue M.P., Rohan T.E., Sandin S., Sandler D.P., Sawada N., Simon T.G., Sinha R., Stolzenberg-Solomon R., and Tsugane S.

Abstract

Background & Aims: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. Method(s): We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. Result(s): During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR >=5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only. Conclusion(s): We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. Lay summary: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic b

Published
2020

85. The risk of ovarian cancer increases with an increase in the lifetime number of ovulatory cycles: An analysis from the Ovarian Cancer Cohort Consortium (OC3).

Author

Rohan T.E., Sandler D.P., Schairer C., Schouten L.J., Setiawan V.W., Swerdlow A.J., Travis R.C., Trichopoulou A., Van Den Brandt P.A., Visvanathan K., Wilkens L.R., Wolk A., Zeleniuch-Jacquotte A., Wentzensen N., Trabert B., Tworoger S.S., O'Brien K.M., Townsend M.K., Fortner R.T., Iversen E.S., Hartge P., White E., Amiano P., Arslan A.A., Bernstein L., Brinton L.A., Buring J.E., Dossus L., Fraser G.E., Gaudet M.M., Giles G.G., Gram I.T., Harris H.R., Bolton J.H., Idahl A., Jones M.E., Kaaks R., Kirsh V.A., Knutsen S.F., Kvaskoff M., Lacey J.V., Lee I.-M., Milne R.L., Onland-Moret N.C., Overvad K., Patel A.V., Peters U., Poynter J.N., Riboli E., Robien K., Rohan T.E., Sandler D.P., Schairer C., Schouten L.J., Setiawan V.W., Swerdlow A.J., Travis R.C., Trichopoulou A., Van Den Brandt P.A., Visvanathan K., Wilkens L.R., Wolk A., Zeleniuch-Jacquotte A., Wentzensen N., Trabert B., Tworoger S.S., O'Brien K.M., Townsend M.K., Fortner R.T., Iversen E.S., Hartge P., White E., Amiano P., Arslan A.A., Bernstein L., Brinton L.A., Buring J.E., Dossus L., Fraser G.E., Gaudet M.M., Giles G.G., Gram I.T., Harris H.R., Bolton J.H., Idahl A., Jones M.E., Kaaks R., Kirsh V.A., Knutsen S.F., Kvaskoff M., Lacey J.V., Lee I.-M., Milne R.L., Onland-Moret N.C., Overvad K., Patel A.V., Peters U., Poynter J.N., Riboli E., and Robien K.

Abstract

Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than womenin the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60-2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10-1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04-1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09-1.17)], endometrioid [1.20 (1.10-1.32)], and clear cell [1.37 (1.18-1.58)], but not mucinous [0.99 (0.88-1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies. Significance: Although ovarian cancer is rare, risk of most ovarian cancers doubles as the number of lifetime ovulatory cycles increases from approx

Published
2020

86. Genome-Wide Gene-Diabetes and Gene-Obesity Interaction Scan in 8,255 Cases and 11,900 Controls from PanScan and PanC4 Consortia

Author

Tang, H, Jiang, L, Stolzenberg-Solomon, RZ, Arslan, AA, Freeman, LEB, Bracci, PM, Brennan, P, Canzian, F, Du, M, Gallinger, S, Giles, GG, Goodman, PJ, Kooperberg, C, Le Marchand, L, Neale, RE, Shu, X-O, Visvanathan, K, White, E, Zheng, W, Albanes, D, Andreotti, G, Babic, A, Bamlet, WR, Berndt, S, Blackford, A, Bueno-de-Mesquita, B, Buring, JE, Campa, D, Chanock, SJ, Childs, E, Duell, EJ, Fuchs, C, Gaziano, JM, Goggins, M, Hartge, P, Hassam, MH, Holly, EA, Hoover, RN, Hung, RJ, Kurtz, RC, Lee, I-M, Malats, N, Milne, RL, Ng, K, Oberg, AL, Orlow, I, Peters, U, Porta, M, Rabe, KG, Rothman, N, Scelo, G, Sesso, HD, Silverman, DT, Thompson, IM, Tjonneland, A, Trichopoulou, A, Wactawski-Wende, J, Wentzensen, N, Wilkens, LR, Yu, H, Zeleniuch-Jacquotte, A, Amundadottir, LT, Jacobs, EJ, Petersen, GM, Wolpin, BM, Risch, HA, Chatterjee, N, Klein, AP, Li, D, Kraft, P, Wei, P, Tang, H, Jiang, L, Stolzenberg-Solomon, RZ, Arslan, AA, Freeman, LEB, Bracci, PM, Brennan, P, Canzian, F, Du, M, Gallinger, S, Giles, GG, Goodman, PJ, Kooperberg, C, Le Marchand, L, Neale, RE, Shu, X-O, Visvanathan, K, White, E, Zheng, W, Albanes, D, Andreotti, G, Babic, A, Bamlet, WR, Berndt, S, Blackford, A, Bueno-de-Mesquita, B, Buring, JE, Campa, D, Chanock, SJ, Childs, E, Duell, EJ, Fuchs, C, Gaziano, JM, Goggins, M, Hartge, P, Hassam, MH, Holly, EA, Hoover, RN, Hung, RJ, Kurtz, RC, Lee, I-M, Malats, N, Milne, RL, Ng, K, Oberg, AL, Orlow, I, Peters, U, Porta, M, Rabe, KG, Rothman, N, Scelo, G, Sesso, HD, Silverman, DT, Thompson, IM, Tjonneland, A, Trichopoulou, A, Wactawski-Wende, J, Wentzensen, N, Wilkens, LR, Yu, H, Zeleniuch-Jacquotte, A, Amundadottir, LT, Jacobs, EJ, Petersen, GM, Wolpin, BM, Risch, HA, Chatterjee, N, Klein, AP, Li, D, Kraft, P, and Wei, P

Abstract

BACKGROUND: Obesity and diabetes are major modifiable risk factors for pancreatic cancer. Interactions between genetic variants and diabetes/obesity have not previously been comprehensively investigated in pancreatic cancer at the genome-wide level. METHODS: We conducted a gene-environment interaction (GxE) analysis including 8,255 cases and 11,900 controls from four pancreatic cancer genome-wide association study (GWAS) datasets (Pancreatic Cancer Cohort Consortium I-III and Pancreatic Cancer Case Control Consortium). Obesity (body mass index ≥30 kg/m2) and diabetes (duration ≥3 years) were the environmental variables of interest. Approximately 870,000 SNPs (minor allele frequency ≥0.005, genotyped in at least one dataset) were analyzed. Case-control (CC), case-only (CO), and joint-effect test methods were used for SNP-level GxE analysis. As a complementary approach, gene-based GxE analysis was also performed. Age, sex, study site, and principal components accounting for population substructure were included as covariates. Meta-analysis was applied to combine individual GWAS summary statistics. RESULTS: No genome-wide significant interactions (departures from a log-additive odds model) with diabetes or obesity were detected at the SNP level by the CC or CO approaches. The joint-effect test detected numerous genome-wide significant GxE signals in the GWAS main effects top hit regions, but the significance diminished after adjusting for the GWAS top hits. In the gene-based analysis, a significant interaction of diabetes with variants in the FAM63A (family with sequence similarity 63 member A) gene (significance threshold P < 1.25 × 10-6) was observed in the meta-analysis (P GxE = 1.2 ×10-6, P Joint = 4.2 ×10-7). CONCLUSIONS: This analysis did not find significant GxE interactions at the SNP level but found one significant interaction with diabetes at the gene level. A larger sample size might unveil additional genetic factors via GxE scans. IMPACT: This study may con

Published
2020

87. The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3)

Author

Trabert, B, Tworoger, SS, O'Brien, KM, Townsend, MK, Fortner, RT, Iversen, ES, Hartge, P, White, E, Amiano, P, Arslan, AA, Bernstein, L, Brinton, LA, Buring, JE, Dossus, L, Fraser, GE, Gaudet, MM, Giles, GG, Gram, IT, Harris, HR, Bolton, JH, Idahl, A, Jones, ME, Kaaks, R, Kirsh, VA, Knutsen, SF, Kvaskoff, M, Lacey, J, Lee, I-M, Milne, RL, Onland-Moret, NC, Overvad, K, Patel, A, Peters, U, Poynter, JN, Riboli, E, Robien, K, Rohan, TE, Sandler, DP, Schairer, C, Schouten, LJ, Setiawan, VW, Swerdlow, AJ, Travis, RC, Trichopoulou, A, van den Brandt, PA, Visvanathan, K, Wilkens, LR, Wolk, A, Zeleniuch-Jacquotte, A, Wentzensen, N, Trabert, B, Tworoger, SS, O'Brien, KM, Townsend, MK, Fortner, RT, Iversen, ES, Hartge, P, White, E, Amiano, P, Arslan, AA, Bernstein, L, Brinton, LA, Buring, JE, Dossus, L, Fraser, GE, Gaudet, MM, Giles, GG, Gram, IT, Harris, HR, Bolton, JH, Idahl, A, Jones, ME, Kaaks, R, Kirsh, VA, Knutsen, SF, Kvaskoff, M, Lacey, J, Lee, I-M, Milne, RL, Onland-Moret, NC, Overvad, K, Patel, A, Peters, U, Poynter, JN, Riboli, E, Robien, K, Rohan, TE, Sandler, DP, Schairer, C, Schouten, LJ, Setiawan, VW, Swerdlow, AJ, Travis, RC, Trichopoulou, A, van den Brandt, PA, Visvanathan, K, Wilkens, LR, Wolk, A, Zeleniuch-Jacquotte, A, and Wentzensen, N

Abstract

Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60-2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10-1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04-1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09-1.17)], endometrioid [1.20 (1.10-1.32)], and clear cell [1.37 (1.18-1.58)], but not mucinous [0.99 (0.88-1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies. SIGNIFICANCE: Although ovarian cancer is rare, risk of most ovarian cancers doubles as the number of lifetime ovulatory cycles increases from appro

Published
2020

88. Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk

Author

Yuan, F, Hung, RJ, Walsh, N, Zhang, H, Platz, EA, Wheeler, W, Song, L, Arslan, AA, Freeman, LEB, Bracci, P, Canzian, F, Du, M, Gallinger, S, Giles, GG, Goodman, PJ, Kooperberg, C, Le Marchand, L, Neale, RE, Rosendahl, J, Scelo, G, Shu, X-O, Visvanathan, K, White, E, Zheng, W, Albanes, D, Amiano, P, Andreotti, G, Babic, A, Bamlet, WR, Berndt, SI, Brennan, P, Bueno-de-Mesquita, B, Buring, JE, Campbell, PT, Chanock, SJ, Fuchs, CS, Gaziano, JM, Goggins, MG, Hackert, T, Hartge, P, Hassan, MM, Holly, EA, Hoover, RN, Katzke, V, Kirsten, H, Kurtz, RC, Lee, I-M, Malats, N, Milne, RL, Murphy, N, Ng, K, Oberg, AL, Porta, M, Rabe, KG, Real, FX, Rothman, N, Sesso, HD, Silverman, DT, Thompson, IM, Wactawski-Wende, J, Wang, X, Wentzensen, N, Wilkens, LR, Yu, H, Zeleniuch-Jacquotte, A, Shi, J, Duell, EJ, Amundadottir, LT, Li, D, Petersen, GM, Wolpin, BM, Risch, HA, Yu, K, Klein, AP, Stolzenberg-Solomon, R, Yuan, F, Hung, RJ, Walsh, N, Zhang, H, Platz, EA, Wheeler, W, Song, L, Arslan, AA, Freeman, LEB, Bracci, P, Canzian, F, Du, M, Gallinger, S, Giles, GG, Goodman, PJ, Kooperberg, C, Le Marchand, L, Neale, RE, Rosendahl, J, Scelo, G, Shu, X-O, Visvanathan, K, White, E, Zheng, W, Albanes, D, Amiano, P, Andreotti, G, Babic, A, Bamlet, WR, Berndt, SI, Brennan, P, Bueno-de-Mesquita, B, Buring, JE, Campbell, PT, Chanock, SJ, Fuchs, CS, Gaziano, JM, Goggins, MG, Hackert, T, Hartge, P, Hassan, MM, Holly, EA, Hoover, RN, Katzke, V, Kirsten, H, Kurtz, RC, Lee, I-M, Malats, N, Milne, RL, Murphy, N, Ng, K, Oberg, AL, Porta, M, Rabe, KG, Real, FX, Rothman, N, Sesso, HD, Silverman, DT, Thompson, IM, Wactawski-Wende, J, Wang, X, Wentzensen, N, Wilkens, LR, Yu, H, Zeleniuch-Jacquotte, A, Shi, J, Duell, EJ, Amundadottir, LT, Li, D, Petersen, GM, Wolpin, BM, Risch, HA, Yu, K, Klein, AP, and Stolzenberg-Solomon, R

Abstract

Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10-6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. SIGNIFICANCE: The joint effects of common variants in genomic regions containing susceptibility loci for infla

Published
2020

94. Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium

Author

Fortner, RT, Poole, EM, Wentzensen, NA, Trabert, B, White, E, Arslan, AA, Patel, A, Setiawan, VW, Visvanathan, K, Weiderpass, E, Adami, H-O, Black, A, Bernstein, L, Brinton, LA, Buring, J, Clendenen, T, Fournier, A, Fraser, G, Gapstur, SM, Gaudet, MM, Giles, GG, Gram, IT, Hartge, P, Hoffman-Bolton, J, Idahl, A, Kaaks, R, Kirsh, VA, Knutsen, S, Koh, W-P, Lacey, JV, Lee, I-M, Lundin, E, Merritt, MA, Milne, RL, Onland-Moret, NC, Peters, U, Poynter, JN, Rinaldi, S, Robien, K, Rohan, T, Sanchez, M-J, Schairer, C, Schouten, LJ, Tjonneland, A, Townsend, MK, Travis, RC, Trichopoulou, A, van den Brandt, PA, Vineis, P, Wilkens, L, Wolk, A, Yang, HP, Zeleniuch-Jacquotte, A, Tworoger, SS, Fortner, RT, Poole, EM, Wentzensen, NA, Trabert, B, White, E, Arslan, AA, Patel, A, Setiawan, VW, Visvanathan, K, Weiderpass, E, Adami, H-O, Black, A, Bernstein, L, Brinton, LA, Buring, J, Clendenen, T, Fournier, A, Fraser, G, Gapstur, SM, Gaudet, MM, Giles, GG, Gram, IT, Hartge, P, Hoffman-Bolton, J, Idahl, A, Kaaks, R, Kirsh, VA, Knutsen, S, Koh, W-P, Lacey, JV, Lee, I-M, Lundin, E, Merritt, MA, Milne, RL, Onland-Moret, NC, Peters, U, Poynter, JN, Rinaldi, S, Robien, K, Rohan, T, Sanchez, M-J, Schairer, C, Schouten, LJ, Tjonneland, A, Townsend, MK, Travis, RC, Trichopoulou, A, van den Brandt, PA, Vineis, P, Wilkens, L, Wolk, A, Yang, HP, Zeleniuch-Jacquotte, A, and Tworoger, SS

Abstract

Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.

Published
2019

95. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author

Klein, A.P. Wolpin, B.M. Risch, H.A. Stolzenberg-Solomon, R.Z. Mocci, E. Zhang, M. Canzian, F. Childs, E.J. Hoskins, J.W. Jermusyk, A. Zhong, J. Chen, F. Albanes, D. Andreotti, G. Arslan, A.A. Babic, A. Bamlet, W.R. Beane-Freeman, L. Berndt, S.I. Blackford, A. Borges, M. Borgida, A. Bracci, P.M. Brais, L. Brennan, P. Brenner, H. Bueno-De-Mesquita, B. Buring, J. Campa, D. Capurso, G. Cavestro, G.M. Chaffee, K.G. Chung, C.C. Cleary, S. Cotterchio, M. Dijk, F. Duell, E.J. Foretova, L. Fuchs, C. Funel, N. Gallinger, S. Gaziano, J.M.M. Gazouli, M. Giles, G.G. Giovannucci, E. Goggins, M. Goodman, G.E. Goodman, P.J. Hackert, T. Haiman, C. Hartge, P. Hasan, M. Hegyi, P. Helzlsouer, K.J. Herman, J. Holcatova, I. Holly, E.A. Hoover, R. Hung, R.J. Jacobs, E.J. Jamroziak, K. Janout, V. Kaaks, R. Khaw, K.-T. Klein, E.A. Kogevinas, M. Kooperberg, C. Kulke, M.H. Kupcinskas, J. Kurtz, R.J. Laheru, D. Landi, S. Lawlor, R.T. Lee, I.-M. Lemarchand, L. Lu, L. Malats, N. Mambrini, A. Mannisto, S. Milne, R.L. Mohelníková-Duchoňová, B. Neale, R.E. Neoptolemos, J.P. Oberg, A.L. Olson, S.H. Orlow, I. Pasquali, C. Patel, A.V. Peters, U. Pezzilli, R. Porta, M. Real, F.X. Rothman, N. Scelo, G. Sesso, H.D. Severi, G. Shu, X.-O. Silverman, D. Smith, J.P. Soucek, P. Sund, M. Talar-Wojnarowska, R. Tavano, F. Thornquist, M.D. Tobias, G.S. Van Den Eeden, S.K. Vashist, Y. Visvanathan, K. Vodicka, P. Wactawski-Wende, J. Wang, Z. Wentzensen, N. White, E. Yu, H. Yu, K. Zeleniuch-Jacquotte, A. Zheng, W. Kraft, P. Li, D. Chanock, S. Obazee, O. Petersen, G.M. Amundadottir, L.T.

Abstract

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: Rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene. © 2018 The Author(s).

Published
2018

97. Analgesic Use and Ovarian Cancer Risk: An Analysis in the Ovarian Cancer Cohort Consortium

Author

Trabert, B, Trabert, B, Poole, EM, White, E, Visvanathan, K, Adami, HO, Anderson, GL, Brasky, TM, Brinton, LA, Fortner, RT, Gaudet, M, Hartge, P, Hoffman-Bolton, J, Jones, M, Lacey, JV, Larsson, SC, Mackenzie, GG, Schouten, LJ, Sandler, DP, O'Brien, K, Patel, AV, Peters, U, Prizment, A, Robien, K, Setiawan, WV, Swerdlow, A, Van Den Brandt, PA, Weiderpass, E, Wilkens, LR, Wolk, A, Wentzensen, N, Tworoger, SS, Trabert, B, Trabert, B, Poole, EM, White, E, Visvanathan, K, Adami, HO, Anderson, GL, Brasky, TM, Brinton, LA, Fortner, RT, Gaudet, M, Hartge, P, Hoffman-Bolton, J, Jones, M, Lacey, JV, Larsson, SC, Mackenzie, GG, Schouten, LJ, Sandler, DP, O'Brien, K, Patel, AV, Peters, U, Prizment, A, Robien, K, Setiawan, WV, Swerdlow, A, Van Den Brandt, PA, Weiderpass, E, Wilkens, LR, Wolk, A, Wentzensen, N, and Tworoger, SS

Published
2018

98. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author

Klein, AP, Wolpin, BM, Risch, HA, Stolzenberg-Solomon, RZ, Mocci, E, Zhang, M, Canzian, F, Childs, EJ, Hoskins, JW, Jermusyk, A, Zhong, J, Chen, F, Albanes, D, Andreotti, G, Arslan, AA, Babic, A, Bamlet, WR, Beane-Freeman, L, Berndt, SI, Blackford, A, Borges, M, Borgida, A, Bracci, PM, Brais, L, Brennan, P, Brenner, H, Bueno-de-Mesquita, B, Buring, J, Campa, D, Capurso, G, Cavestro, GM, Chaffee, KG, Chung, CC, Cleary, S, Cotterchio, M, Dijk, F, Duell, EJ, Foretova, L, Fuchs, C, Funel, N, Gallinger, S, Gaziano, JMM, Gazouli, M, Giles, GG, Giovannucci, E, Goggins, M, Goodman, GE, Goodman, PJ, Hackert, T, Haiman, C, Hartge, P, Hasan, M, Hegyi, P, Helzlsouer, KJ, Herman, J, Holcatova, I, Holly, EA, Hoover, R, Hung, RJ, Jacobs, EJ, Jamroziak, K, Janout, V, Kaaks, R, Khaw, K-T, Klein, EA, Kogevinas, M, Kooperberg, C, Kulke, MH, Kupcinskas, J, Kurtz, RJ, Laheru, D, Landi, S, Lawlor, RT, Lee, I-M, LeMarchand, L, Lu, L, Malats, N, Mambrini, A, Mannisto, S, Milne, RL, Mohelnikova-Duchonova, B, Neale, RE, Neoptolemos, JP, Oberg, AL, Olson, SH, Orlow, I, Pasquali, C, Patel, AV, Peters, U, Pezzilli, R, Porta, M, Real, FX, Rothman, N, Scelo, G, Sesso, HD, Severi, G, Shu, X-O, Silverman, D, Smith, JP, Soucek, P, Sund, M, Talar-Wojnarowska, R, Tavano, F, Thornquist, MD, Tobias, GS, Van Den Eeden, SK, Vashist, Y, Visvanathan, K, Vodicka, P, Wactawski-Wende, J, Wang, Z, Wentzensen, N, White, E, Yu, H, Yu, K, Zeleniuch-Jacquotte, A, Zheng, W, Kraft, P, Li, D, Chanock, S, Obazee, O, Petersen, GM, Amundadottir, LT, Klein, AP, Wolpin, BM, Risch, HA, Stolzenberg-Solomon, RZ, Mocci, E, Zhang, M, Canzian, F, Childs, EJ, Hoskins, JW, Jermusyk, A, Zhong, J, Chen, F, Albanes, D, Andreotti, G, Arslan, AA, Babic, A, Bamlet, WR, Beane-Freeman, L, Berndt, SI, Blackford, A, Borges, M, Borgida, A, Bracci, PM, Brais, L, Brennan, P, Brenner, H, Bueno-de-Mesquita, B, Buring, J, Campa, D, Capurso, G, Cavestro, GM, Chaffee, KG, Chung, CC, Cleary, S, Cotterchio, M, Dijk, F, Duell, EJ, Foretova, L, Fuchs, C, Funel, N, Gallinger, S, Gaziano, JMM, Gazouli, M, Giles, GG, Giovannucci, E, Goggins, M, Goodman, GE, Goodman, PJ, Hackert, T, Haiman, C, Hartge, P, Hasan, M, Hegyi, P, Helzlsouer, KJ, Herman, J, Holcatova, I, Holly, EA, Hoover, R, Hung, RJ, Jacobs, EJ, Jamroziak, K, Janout, V, Kaaks, R, Khaw, K-T, Klein, EA, Kogevinas, M, Kooperberg, C, Kulke, MH, Kupcinskas, J, Kurtz, RJ, Laheru, D, Landi, S, Lawlor, RT, Lee, I-M, LeMarchand, L, Lu, L, Malats, N, Mambrini, A, Mannisto, S, Milne, RL, Mohelnikova-Duchonova, B, Neale, RE, Neoptolemos, JP, Oberg, AL, Olson, SH, Orlow, I, Pasquali, C, Patel, AV, Peters, U, Pezzilli, R, Porta, M, Real, FX, Rothman, N, Scelo, G, Sesso, HD, Severi, G, Shu, X-O, Silverman, D, Smith, JP, Soucek, P, Sund, M, Talar-Wojnarowska, R, Tavano, F, Thornquist, MD, Tobias, GS, Van Den Eeden, SK, Vashist, Y, Visvanathan, K, Vodicka, P, Wactawski-Wende, J, Wang, Z, Wentzensen, N, White, E, Yu, H, Yu, K, Zeleniuch-Jacquotte, A, Zheng, W, Kraft, P, Li, D, Chanock, S, Obazee, O, Petersen, GM, and Amundadottir, LT

Abstract

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.

Published
2018

100. Epidemiology of Intraocular Melanoma

Author

Tucker, M. A., Hartge, P., Shields, J. A., Herfarth, Ch., editor, Senn, H. J., editor, Baum, M., editor, Diehl, V., editor, von Essen, C., editor, Grundmann, E., editor, Hitzig, W., editor, Rajewsky, M. F., editor, and Gallagher, Richard P., editor

Published
1986
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results