Sequence variants of estrogen receptor β and risk of prostate cancer in the national cancer institute breast and prostate cancer cohort consortium
Sequence variants of estrogen receptor β and risk of prostate cancer in the national cancer institute breast and prostate cancer cohort consortium
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DOI：
10.1158/1055-9965.epi-07-0431
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发表时间：
2007-10-01
影响因子：
3.8
通讯作者：
Weinstein, Stephanie J.
中科院分区：
文献类型：
--
作者：
Chen, Yen-Ching;Kraft, Peter;Weinstein, Stephanie J.
背景资料：雌激素受体β（ESR 2）可能发挥作用，通过调节相关基因的细胞增殖和apoptosis.Methods：我们进行了巢式病例对照研究，在乳腺癌和前列腺癌队列联盟（BPC 3），汇集了8，323例前列腺癌病例和9，412对照组从7个队列。白人是主要种族。我们通过对190例乳腺癌和前列腺癌病例的外显子进行重测序，并对349例无癌症受试者的多种族小组中跨越该位点的一组密集单核苷酸多态性（SNP）进行基因分型，来表征ESR 2的遗传变异。我们选择了四个单倍型标记SNP（htSNP）来捕获白人中常见的ESR 2变异;然后在所有队列中对这些htSNP进行基因分型。使用条件logistic回归模型评估ESR 2序列变异与前列腺癌风险之间的关联。我们还研究了年龄、体重指数和家族史对效应的影响，以及ESR 2序列变异体与晚期（>= T3 b、N-1或M-1）和高级别（Gleason总和>= 8）前列腺癌的相关性。任何单倍型对前列腺癌风险影响的总体检验均不显著（P = 0.31）。然而，我们观察到，携带两个拷贝的一个变异单倍型（TACC）的男性患前列腺癌的风险增加了1.46倍（99%置信区间，1.06-2.01），与携带零拷贝的这种变异单倍型的男性相比。没有SNPs或单倍型与晚期或高级别的前列腺癌。结论：在我们的分析集中在白人常见的遗传变异，我们观察到很少有证据表明ESR 2的遗传变异与前列腺癌的风险有任何实质性的关联。在隐性模型下，TACC单倍型和前列腺癌风险之间名义上显著（P < 0.01）的相关性可能是偶然发现，并且在任何情况下，似乎对前列腺癌的总体负担只有轻微的贡献。
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.