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BRCA1 和 VDR 基因多态性与墨西哥男性前列腺癌风险相关。

BRCA1 and VDR gene polymorphisms are associated with prostate cancer risk in Mexican men.

机构信息

Synovial Liquid Laboratory, National Institute of Rehabilitation "Luis Guillermo Ibarra Ibarra" (INR), Mexico City, Mexico.

Research Center for Infectious Diseases (CISEI), Genetic Epidemiology Department, National Institute of Public Health (INSP), Cuernavaca, Morelos, Mexico.

出版信息

Mol Carcinog. 2020 Jun;59(6):629-639. doi: 10.1002/mc.23187. Epub 2020 Mar 26.

Abstract

Prostate cancer (PC) is a polygenic disease with broad differences across ethnicities. BRCA1/2 and VDR have exhibited a featured genetic contribution to PC development in European populations. Nonetheless, its contribution in Latino populations specifically among Mexican men, where 70% of PC cases are detected in advanced stages, is still unknown. The contribution of seven polymorphisms in BRCA1/2 and VDR genes to PC susceptibility was evaluated in 370 incident PC cases and 759 age-matched (±5 years) controls belonging to the Mexican population. Based on Gleason score at diagnosis, PC cases were classified as well-differentiated PC (Gleason <7) and moderate or poorly differentiated PC (Gleason ≥7). Age at diagnosis was used to divided PC cases in earlier (<60 years) and late-onset PC (≥60 years). Prostate and breast cancer family histories were obtained through interview. Our results provided evidences about the contribution of BRCA1-rs1799966 (OR  = 2.30; 95% confidence interval [CI] = 1.36-3.91) to the moderate or poorly differentiated PC risk, independently of the family history of prostate, breast or ovary cancer. Further, VDR-rs2238135-G allele was associated with early-onset PC (OR  = 2.05; 95% CI = 1.06-3.95), and marginally with moderate or poorly differentiated PC risk. The present study revealed the crucial role of BRCA1 in PC aggressiveness risk, outstanding the gender imbalance regarding the breast cancer risk in women.

摘要

前列腺癌(PC)是一种多基因疾病,在不同种族之间存在广泛差异。BRCA1/2 和 VDR 在欧洲人群中表现出对 PC 发展的特征遗传贡献。然而,其在拉丁裔人群中的贡献,特别是在墨西哥男性中,70%的 PC 病例在晚期被发现,仍不清楚。在属于墨西哥人群的 370 例新发 PC 病例和 759 例年龄匹配(±5 岁)对照中,评估了 BRCA1/2 和 VDR 基因中的七个多态性对 PC 易感性的贡献。根据诊断时的 Gleason 评分,将 PC 病例分为分化良好的 PC(Gleason<7)和中或低分化 PC(Gleason≥7)。使用诊断时的年龄将 PC 病例分为早发(<60 岁)和晚发 PC(≥60 岁)。通过访谈获得前列腺癌和乳腺癌家族史。我们的研究结果提供了证据表明,BRCA1-rs1799966(OR=2.30;95%置信区间[CI]=1.36-3.91)对中或低分化 PC 风险的贡献,独立于前列腺癌、乳腺癌或卵巢癌家族史。此外,VDR-rs2238135-G 等位基因与早发 PC(OR=2.05;95%CI=1.06-3.95)相关,与中或低分化 PC 风险相关。本研究揭示了 BRCA1 在 PC 侵袭性风险中的关键作用,突出了女性乳腺癌风险的性别不平衡。

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