Possible risk modifications in the association between MnSOD Ala-9Val polymorphism and breast cancer risk: subgroup analysis and evidence-based sample size calculation for a future trial
Possible risk modifications in the association between MnSOD Ala-9Val polymorphism and breast cancer risk: subgroup analysis and evidence-based sample size calculation for a future trial
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MnSOD Ala-9Val 多态性与乳腺癌风险之间关联的可能风险修改：未来试验的亚组分析和基于证据的样本量计算
DOI：
10.1007/s10549-010-0978-9
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发表时间：
2011-01-01
影响因子：
3.8
通讯作者：
Pei, Jianping
中科院分区：
文献类型：
--
作者：
Chen, Yun;Pei, Jianping
锰超氧化物歧化酶（MnSOD）已被确定为活性氧（ROS）的重要清除剂，活性氧（ROS）可导致氧化应激，进而导致乳腺癌。随后的一些基于人群的研究调查了MnSOD Ala-9Val多态性与乳腺癌风险之间的关联。然而，这些研究得出了相互矛盾的结果。提示MnSOD基因Ala-9Val多态性对乳腺癌易感性的影响可能受到其他危险因素的影响。为了提供更明确的结论，首先使用传统方法和贝叶斯方法进行了一项完整的荟萃分析，结合并总结了16项研究。在这一步骤中，在生物学证明后确定了隐性遗传模式。贝叶斯方法的能力在合并优势比和95%置信区间的估计中得到了强调。因此，未观察到显著关联（OR = 0.978，CI = 0.914-1.046）。然后进行贝叶斯元回归和亚组分析，以发现其他因素可能的风险修正，包括绝经状态，种族效应，口服避孕药的使用，激素替代疗法的使用，水果和蔬菜的摄入，维生素补充剂和体重指数。虽然大多数亚组的把握度可能不足以做出统计学声明，但基于更新的荟萃分析进行了基于证据的样本量计算，以把握未来的试验。例如，一项新的亚洲研究需要约5,000例受试者（2,500例病例和2,500例对照）才能达到80%的把握度。
Manganese superoxide dismutase (MnSOD) has been identified as an important scavenger of reactive oxygen species (ROS), which can cause oxidative stress followed by breast cancer. A number of subsequent population-based studies have investigated the association between MnSOD Ala-9Val polymorphism and the risk of breast cancer. However, these studies have yielded conflicting results. This fact implies that the effect of MnSOD Ala-9Val polymorphism on the susceptibility to breast cancer may be modified by other risk factors. To provide a more definitive conclusion, a full meta-analysis combining and summarizing 16 studies was first performed using both traditional and Bayesian approaches. During this step, a recessive inheritance mode was determined after a biological justification. The capability of the Bayesian method was highlighted in the estimation of a pooled odds ratio and 95% confidence interval. As a result, no significant association was observed (OR = 0.978, CI = 0.914–1.046). Bayesian meta-regression and subgroup analysis were then conducted to find possible risk modifications by other factors, including menopausal status, ethnicity effect, use of oral contraceptives, use of hormone replacement therapy, fruits and vegetables intake, vitamin supplement, and body mass index. While the power of most subgroups may be insufficient to make a statistical statement, an evidence-based sample size calculation based upon updated meta-analysis was performed to power a future trial. For example, approximately 5,000 subjects are required for a new Asian study (2,500 cases and 2,500 controls) to achieve 80% power.