Effect of lifestyle and single nucleotide polymorphisms on breast cancer risk: A case-control study in Japanese women

【背景】生活方式，包括饮食和体育活动，以及出生/母乳喂养史都是影响乳腺癌风险的因素。一些报道也提出了单核苷酸多态性（snp）与乳腺癌风险之间的相关性，但基因-环境相互作用与乳腺癌风险的关系尚未得到广泛研究。[方法]选取476例乳腺癌患者和528例无乳腺癌病史的对照组。生活方式调查采用了一份包含48个问题的调查问卷，内容涉及饮食、体育活动、吸烟习惯、饮酒、分娩/母乳喂养史等。基于以往的报道，我们利用血液样本分析了6个snp (TNRC9-rs3803662、LSP1/11q-rs3817198、MAP3K1-rs889312、8q24-rs13281615、5p12-rs981782和tgf - β1-rs1800470)，并通过多元logistic回归分析计算了年龄调整后的优势比。【结果】研究时间为2010年12月至2011年11月。与乳腺癌发生有显著相关性的生活方式因素（年龄调整优势比，[95%可信区间]）包括：BMI（1.041,[1.00 - 1.08]）、吸烟史（2.28,[1.45 - 3.65]）、生育数量少（1.18,[1.05 - 1.34]）、闲暇时间不运动（1.36,[1.06 - 1.77]）、绿色和黄色蔬菜摄入少（1.69,[1.01 - 2.85]）、蘑菇摄入少（1.58,[1.05 - 2.39]）。基于绝经状态的分层分析显示，吸烟史（1.85,[1.00 - 3.49]）和低绿色和黄色蔬菜摄入量（2.5,[1.03 - 5.88]）是绝经前的显著危险因素，吸烟史（2.28,[1.45 - 3.65]）、低绿色和黄色蔬菜摄入量（2.24,[1.09 - 4.68]）、闲暇时间不运动（1.67,[1.19 - 2.36]）、少生育（1.49,[1.25 - 1.78]）、无母乳喂养史（1.03,1.00 - 3.49]）是绝经前的显著危险因素。[1.01 - 1.06])是绝经后的重要危险因素。SNP分析结果提示TNRC9-rs3803662是绝经前女性的重要危险因素（2.29,[1.25 - 4.25]）。然而，在包括生活方式因素和snp在内的多变量分析中，只有吸烟史成为绝经前女性的重要危险因素。【结论】本研究发现生活方式与乳腺癌风险之间存在相关性，与之前的研究结果一致。作为乳腺癌的危险因素，生活方式和环境因素，如出生和母乳喂养可能比snp更重要。少

[Background] Lifestyle, including diet and physical activity, and birth/breastfeeding history are known to affectthe risk for breast cancer. A correlation between single nucleotide polymorphisms (SNPs) and breast cancer risk has also been suggested in some reports, but the gene-environment interaction with breast cancer risk has not been examined widely.[Methods] The subjects were 476 breast cancer patients and 528 controls who attended a health check and had no history of breast cancer. Lifestyle was examined using a questionnaire with 48 questions about diet, physical activity, smoking habits, alcohol intake, and birth/breastfeeding history, etc. Based on past reports, we analyzed 6 SNPs (TNRC9-rs3803662,LSP1/11q-rs3817198, MAP3K1-rs889312, 8q24-rs13281615, 5p12-rs981782, and TGFβ1-rs1800470) using blood samples, and calculated age-adjusted odds ratios in a multiple logistic regression analysis. [Results] The study was performed from December 2010 to November 2011. Lifestyle factors … More (age-adjusted odds ratio, [95% confident interval]) found to have a significant correlation with development of breast cancer included BMI (1.041, [1.00 - 1.08]), smoking history (2.28, [1.45 - 3.65]), small number of births (1.18, [1.05 - 1.34]), no exercise during leisure time (1.36, [1.06 - 1.77]), low intake of green and yellow vegetables (1.69, [1.01 - 2.85]), and low intake of mushrooms (1.58, [1.05 - 2.39]). Stratified analysis based on menopause status showed that smoking history (1.85, [1.00 - 3.49]) and low intake of green and yellow vegetables (2.5, [1.03 - 5.88]) were significant risk factors before menopause, and that smoking history (2.28, [1.45 - 3.65]),low intake of green and yellow vegetables (2.24, [1.09 - 4.68]), no exercise during leisure time (1.67, [1.19 - 2.36]), small number of births (1.49, [1.25 - 1.78]), and no breastfeeding history (1.03, [1.01 - 1.06]) were significant risk factors after menopause. The results of SNP analysis suggested that TNRC9-rs3803662 was a significant risk factor in women before menopause (2.29, [1.25 - 4.25]). However, in multivariate analysis including lifestyle factors and SNPs, only smoking history emerged as a significant risk factor in women before menopause. [Conclusion] A correlation between lifestyle and breast cancer risk was found in this study, consistent with previous findings. Lifestyle and environmental factors such as births and breastfeeding may be more important than SNPs as risk factors for breast cancer. Less