Université de Lyon , Lyon , France.
Free Radic Res. 2014 Mar;48(3):380-6. doi: 10.3109/10715762.2013.875168. Epub 2014 Jan 23.
Both endogenous factors (genomic variations) and exogenous factors (environmental exposures, lifestyle) impact the balance of reactive oxygen species (ROS). Variants of the ND3 (rs2853826; G10398A) gene of the mitochondrial genome, manganese superoxide dismutase (MnSOD; rs4880 Val16Ala) and glutathione peroxidase (GPX-1; rs1050450 Pro198Leu), are purported to have functional effects on regulation of ROS balance. In this study, we examined associations of breast and prostate cancer risks and survival with these variants, and interactions between rs4880-rs1050450, and alcohol consumption-rs2853826. Nested case-control studies were conducted in the Breast and Prostate Cancer Cohort Consortium (BPC3), consisting of nine cohorts. The analyses included over 10726 post-menopausal breast and 7532 prostate cancer cases with matched controls. Logistic regression models were used to evaluate associations with risk, and proportional hazard models were used for survival outcomes. We did not observe significant interactions between polymorphisms in MnSOD and GPX-1, or between mitochondrial polymorphisms and alcohol intake and risk of either breast (p-interaction of 0.34 and 0.98, respectively) or prostate cancer (p-interaction of 0.49 and 0.50, respectively). We observed a weak inverse association between prostate cancer risk and GPX-1 Leu198Leu carriers (OR 0.87, 95% CI 0.79-0.97, p = 0.01). Overall survival among women with breast cancer was inversely associated with G10398 carriers who consumed alcohol (HR 0.66 95% CI 0.49-0.88). Given the high power in our study, it is unlikely that interactions tested have more than moderate effects on breast or prostate cancer risk. Observed associations need both further epidemiological and biological confirmation.
内源性因素（基因组变异）和外源性因素（环境暴露、生活方式）都会影响活性氧（ROS）的平衡。线粒体基因组 ND3（rs2853826；G10398A）基因、锰超氧化物歧化酶（MnSOD；rs4880 Val16Ala）和谷胱甘肽过氧化物酶（GPX-1；rs1050450 Pro198Leu）的变体被认为对 ROS 平衡的调节具有功能影响。在这项研究中，我们研究了这些变体与乳腺癌和前列腺癌风险和生存的关联，以及 rs4880-rs1050450 之间以及酒精摄入-rs2853826 之间的相互作用。在乳腺癌和前列腺癌队列联盟（BPC3）中进行了嵌套病例对照研究，该联盟由九个队列组成。分析包括超过 10726 名绝经后乳腺癌和 7532 名前列腺癌病例与匹配对照。逻辑回归模型用于评估与风险的关联，比例风险模型用于生存结果。我们没有观察到 MnSOD 和 GPX-1 之间的多态性、或线粒体多态性与酒精摄入之间的相互作用与乳腺癌（p 相互作用分别为 0.34 和 0.98）或前列腺癌（p 相互作用分别为 0.49 和 0.50）的风险之间存在显著相互作用。我们观察到前列腺癌风险与 GPX-1 Leu198Leu 携带者之间存在微弱的负相关（OR 0.87，95%CI 0.79-0.97，p=0.01）。乳腺癌女性的总生存与饮酒的 G10398 携带者呈负相关（HR 0.66 95%CI 0.49-0.88）。考虑到我们研究的高功效，测试的相互作用不太可能对乳腺癌或前列腺癌风险产生超过中等程度的影响。观察到的关联需要进一步的流行病学和生物学确认。
