Genetic variants in genes related to inflammation, apoptosis and autophagy in breast cancer risk

BackgroundInflammation contributes to breast cancer development through its effects on cell damage. This damage is usually dealt with by key genes involved in apoptosis and autophagy pathways.MethodsWe tested 206 single nucleotide polymorphisms (SNPs) in 54 genes related to inflammation, apoptosis and autophagy in a population-based breast cancer study of women of European (658 cases and 795 controls) and East Asian (262 cases and 127 controls) descent. Logistic regression was used to estimate odds ratios for breast cancer risk, and case-only analysis to compare breast cancer subtypes (defined by ER/PR/HER2 status), with adjustment for confounders. We assessed statistical interactions between the SNPs and lifestyle factors (smoking status, physical activity and body mass index).Results and conclusionAlthough no SNP was associated with breast cancer risk among women of European descent, we found evidence for an association among East Asians for rs1800925 (IL-13) and breast cancer risk (OR = 2.08; 95% CI: 1.32–3.28; p = 0.000779), which remained statistically significant after multiple testing correction (padj = 0.0350). This association was replicated in a meta-analysis of 4305 cases and 4194 controls in the Shanghai Breast Cancer Genetics Study (OR 1.12, 95% CI: 1.03–1.21, p = 0.011). Further, we found evidence of an interaction between rs7874234 (TSC1) and physical activity among women of East Asian descent.背景：炎症可通过影响细胞损伤进程参与乳腺癌的发生发展。此类细胞损伤通常由凋亡（apoptosis）与自噬（autophagy）通路中的关键基因介导清除。 方法：本研究针对欧洲裔（658例病例、795例对照）与东亚裔（262例病例、127例对照）女性开展基于人群的乳腺癌研究，对炎症、凋亡及自噬相关的54个基因中的206个单核苷酸多态性（single nucleotide polymorphisms, SNPs）进行了分型检测。采用逻辑回归（logistic regression）模型估算乳腺癌风险的比值比（odds ratios, ORs），并通过仅病例分析比较由雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER2）状态定义的乳腺癌亚型，同时对混杂因素进行校正。此外，本研究还评估了单核苷酸多态性与生活方式因素（吸烟状态、体力活动、体质量指数）之间的统计学交互作用。 结果与结论：尽管在欧洲裔女性人群中未发现任何单核苷酸多态性与乳腺癌风险存在关联，但在东亚裔人群中，我们发现rs1800925（白细胞介素13，IL-13）与乳腺癌风险存在显著关联（OR=2.08；95%置信区间CI：1.32~3.28；p=0.000779），该关联经多重检验校正后仍具有统计学意义（padj=0.0350）。上海乳腺癌遗传学研究（Shanghai Breast Cancer Genetics Study）针对4305例病例与4194例对照开展的荟萃分析（meta-analysis）重复验证了这一关联（OR=1.12，95%CI：1.03~1.21，p=0.011）。此外，我们还发现东亚裔女性中rs7874234（结节性硬化症1，TSC1）与体力活动之间存在交互作用。