TY - JOUR
T1 - Sequence variants of estrogen receptor B and risk of prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
AU - Chen, Yen Ching
AU - Kraft, Peter
AU - Bretsky, Philip
AU - Ketkar, Shamika
AU - Hunter, David J.
AU - Albanes, Demetrius
AU - Altshuler, David
AU - Andriole, Gerald
AU - Berg, Christine D.
AU - Boeing, Heiner
AU - Burtt, Noel
AU - Bueno-de-Mesquita, Bas
AU - Cann, Howard
AU - Canzian, Federico
AU - Chanock, Stephen
AU - Dunning, Alison
AU - Feigelson, Heather S.
AU - Freedman, Matthew
AU - Gaziano, J. Michael
AU - Giovannucci, Edward
AU - Sánchez, Maria Jose
AU - Haiman, Christopher A.
AU - Hallmans, Göran
AU - Hayes, Richard B.
AU - Henderson, Brian E.
AU - Hirschhorn, Joel
AU - Kaaks, Rudolf
AU - Key, Timothy J.
AU - Kolonel, Laurence N.
AU - Lemarchand, Loic
AU - Ma, Jing
AU - Overvad, Kim
AU - Palli, Domenico
AU - Pharaoh, Paul
AU - Pike, Malcolm
AU - Riboli, Eliot
AU - Rodriguez, Carmen
AU - Setiawan, V. Wendy
AU - Stampfer, Meir
AU - Stram, Daniel O.
AU - Thomas, Gilles
AU - Thun, Michael J.
AU - Travis, Ruth C.
AU - Virtamo, Jarmo
AU - Trichopoulou, Antonia
AU - Wacholder, Sholom
AU - Weinstein, Stephanie J.
PY - 2007/10/1
Y1 - 2007/10/1
N2 - Background: Estrogen receptor β (ESR2) may play a role in modulating prostate carcinogenesis through the regulation of genes related to cell proliferation and apoptosis. Methods: We conducted nested case-control studies in the Breast and Prostate Cancer Cohort Consortium (BPC3) that pooled 8,323 prostate cancer cases and 9,412 controls from seven cohorts. Whites were the predominant ethnic group. We characterized genetic variation in ESR2 by resequencing exons in 190 breast and prostate cancer cases and genotyping a dense set of single nucleotide polymorphisms (SNP) spanning the locus in a multiethnic panel of 349 cancer-free subjects. We selected four haplotype-tagging SNPs (htSNP) to capture common ESR2 variation in Whites; these htSNPs were then genotyped in all cohorts. Conditional logistic regression models were used to assess the association between sequence variants of ESR2 and the risk of prostate cancer. We also investigated the effect modification by age, body mass index, and family history, as well as the association between sequence variants of ESR2 and advanced-stage (≥T3b, N1, or M1) and high-grade (Gleason sum ≥8) prostate cancer, respectively. Results: The four tag SNPs in ESR2 were not significantly associated with prostate cancer risk, individually. The global test for the influence of any haplotype on the risk of prostate cancer was not significant (P = 0.31). However, we observed that men carrying two copies of one of the variant haplotypes (TACC) had a 1.46-fold increased risk of prostate cancer (99% confidence interval, 1.06-2.01) compared with men carrying zero copies of this variant haplotype. No SNPs or haplotypes were associated with advanced stage or high grade of prostate cancer. Conclusion: In our analysis focused on genetic variation common in Whites, we observed little evidence for any substantial association of inherited variation in ESR2 with risk of prostate cancer. A nominally significant (P < 0.01) association between the TACC haplotype and prostate cancer risk under the recessive model could be a chance finding and, in any event, would seem to contribute only slightly to the overall burden of prostate cancer.
AB - Background: Estrogen receptor β (ESR2) may play a role in modulating prostate carcinogenesis through the regulation of genes related to cell proliferation and apoptosis. Methods: We conducted nested case-control studies in the Breast and Prostate Cancer Cohort Consortium (BPC3) that pooled 8,323 prostate cancer cases and 9,412 controls from seven cohorts. Whites were the predominant ethnic group. We characterized genetic variation in ESR2 by resequencing exons in 190 breast and prostate cancer cases and genotyping a dense set of single nucleotide polymorphisms (SNP) spanning the locus in a multiethnic panel of 349 cancer-free subjects. We selected four haplotype-tagging SNPs (htSNP) to capture common ESR2 variation in Whites; these htSNPs were then genotyped in all cohorts. Conditional logistic regression models were used to assess the association between sequence variants of ESR2 and the risk of prostate cancer. We also investigated the effect modification by age, body mass index, and family history, as well as the association between sequence variants of ESR2 and advanced-stage (≥T3b, N1, or M1) and high-grade (Gleason sum ≥8) prostate cancer, respectively. Results: The four tag SNPs in ESR2 were not significantly associated with prostate cancer risk, individually. The global test for the influence of any haplotype on the risk of prostate cancer was not significant (P = 0.31). However, we observed that men carrying two copies of one of the variant haplotypes (TACC) had a 1.46-fold increased risk of prostate cancer (99% confidence interval, 1.06-2.01) compared with men carrying zero copies of this variant haplotype. No SNPs or haplotypes were associated with advanced stage or high grade of prostate cancer. Conclusion: In our analysis focused on genetic variation common in Whites, we observed little evidence for any substantial association of inherited variation in ESR2 with risk of prostate cancer. A nominally significant (P < 0.01) association between the TACC haplotype and prostate cancer risk under the recessive model could be a chance finding and, in any event, would seem to contribute only slightly to the overall burden of prostate cancer.
UR - http://www.scopus.com/inward/record.url?scp=35448930679&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-07-0431
DO - 10.1158/1055-9965.EPI-07-0431
M3 - Article
C2 - 17932344
AN - SCOPUS:35448930679
SN - 1055-9965
VL - 16
SP - 1973
EP - 1981
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 10
ER -