Memorial Sloan-Kettering Cancer Center (MSKCC): Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America (TK, MG, KO); Department of Environmental Medicine, New York University Cancer Institute, New York University, New York, New York, United States of America (TK), American Cancer Society, Atlanta, Georgia, United States of America (MG).
PLoS One. 2012;7(6):e35706. doi: 10.1371/journal.pone.0035706. Epub 2012 Jun 29.
Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.
最近，研究人员报道称位于 6 号染色体 6q22.33 上的 rs2180341 与阿什肯纳兹犹太人（AJ）人群中的乳腺癌风险增加相关，而且这种关联也在非 AJ 欧洲血统的人群中观察到。在本研究中，我们使用来自 25 项乳腺癌协会联盟（BCAC）研究的 31428 例浸润性乳腺癌病例和 34700 例对照数据，对 rs2180341 进行了大规模的复制分析。此外，我们还评估了 rs2180341 是否会在来自 11 个中心的 11 个中心的 BRCA1/2 修饰物研究人员联合会（CIMBA）的 3361 名 BRCA1 携带者和 2020 名 BRCA2 携带者中改变乳腺癌风险。基于欧洲裔女性的 BCAC 数据，我们发现 rs2180341 与乳腺癌风险之间存在微弱关联（每个等位基因的比值比（OR）=1.03，95%CI 1.00-1.06，p=0.023）。研究之间存在 OR 异质性的证据（I（2）=49.3%；p=0.004）。在 CIMBA 中，我们观察到 rs2180341 的次要等位基因与 BRCA1 突变携带者的乳腺癌风险呈负相关（每个等位基因的 OR=0.89，95%CI 0.80-1.00，p=0.048），表明该等位基因可能具有潜在的保护作用。这些数据表明 6q22.33 对乳腺癌风险有微弱的影响。
