Genetic & Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Cancer Epidemiol Biomarkers Prev. 2011 Oct;20(10):2222-31. doi: 10.1158/1055-9965.EPI-11-0569. Epub 2011 Jul 27.
The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium.
Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression.
For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08-1.14, P = 7 × 10(-18)) for invasive breast cancer and 1.10 (95% CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99-1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12-1.20, P = 1 × 10(-18) vs. OR = 1.03, 95% CI = 0.99-1.07, P = 0.2 for PR-negative disease; P(heterogeneity) = 2 × 10(-7)); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14-1.25), 1.13 (1.09-1.16), and 1.04 (0.99-1.08) for grade 1, 2, and 3/4, respectively; P(trend) = 5 × 10(-7)].
5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer.
Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants.
单核苷酸多态性（SNP）5p12-rs10941679 已被发现与乳腺癌风险相关，尤其是雌激素受体（ER）阳性疾病。我们旨在进一步探讨该关联在乳腺癌协会联盟中的总体情况，以及通过肿瘤组织病理学。
数据来自 37 项研究，包括 40972 例浸润性病例、1398 例导管原位癌（DCIS）和 46334 例对照，所有病例均为白人欧洲血统，还包括 3007 例亚洲血统的浸润性病例和 2337 例对照。使用逻辑回归评估总体以及肿瘤侵袭性和组织病理学的关联。
对于白人欧洲人，与 5p12-rs10941679 相关的每个等位基因的比值比（OR）为 1.11（95%置信区间[CI] = 1.08-1.14，P = 7×10(-18))，用于浸润性乳腺癌，1.10（95%置信区间[CI] = 1.01-1.21，P = 0.03）用于 DCIS。对于亚洲女性，侵袭性疾病的估计 OR 相似（OR = 1.07，95%CI = 0.99-1.15，P = 0.09）。进一步的分析表明，白人欧洲人的关联主要局限于孕激素受体（PR）阳性疾病（每个等位基因的 OR = 1.16，95%CI = 1.12-1.20，P = 1×10(-18)与 PR 阴性疾病的 OR = 1.03，95%CI = 0.99-1.07，P = 0.2；P（异质性）= 2×10(-7)）；一旦考虑了 PR 状态，ER 状态的异质性不明显（P = 0.2）。该关联在较低分级肿瘤中也更强[每个等位基因的比值比（95%CI）= 1.20（1.14-1.25）、1.13（1.09-1.16）和 1.04（0.99-1.08）分别为 1 级、2 级和 3/4 级；P（趋势）= 5×10(-7)]。
5p12 是 PR 阳性、低级别乳腺癌的乳腺癌易感基因座。
需要对该区域进行多中心精细映射研究，作为识别因果变异或变异的第一步。
