Περίληψη:
Background: Estrogen receptor beta (ESR2) may play a role in modulating
prostate carcirtogenesis 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, N-1, or M-1) 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.
Συγγραφείς:
Chen, Yen-Ching
Kraft, Peter
Bretsky, Philip
Ketkar, Shamika
and Hunter, David J.
Albanes, Demetrius
Altshuler, David and
Andriole, Gerald
Berg, Christine D.
Boeing, Heiner
Burtt,
Noel
Bueno-de-Mesquita, Bas
Cann, Howard
Canzian, Federico
and Chanock, Stephen
Dunning, Alison
Feigelson, Heather S. and
Freedman, Matthew
Gaziano, J. Michael
Giovannucci, Edward and
Sanchez, Maria-Jose
Haiman, Christopher A.
Hallmans, Goran and
Hayes, Richard B.
Henderson, Brian E.
Hirschhorn, Joel and
Kaaks, Rudolf
Key, Timothy J.
Kolonel, Laurence N. and
LeMarchand, Loic
Ma, Jing
Overvad, Kim
Palli, Domenico and
Pharaoh, Paul
Pike, Malcolm
Riboli, Eliot
Rodriguez, Carmen
and Setiawan, V. Wendy
Stampfer, Meir
Stram, Daniel O. and
Thomas, Gilles
Thun, Michael J.
Travis, Ruth C.
Virtamo,
Jarmo
Trichopouiou, Antonia
Wacholder, Sholom
Weinstein,
Stephanie J.
