Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Breast. 2013 Oct;22(5):817-23. doi: 10.1016/j.breast.2013.02.008. Epub 2013 Mar 13.
We assessed whether variants in 22 oxidative stress-related genes are associated with mortality of breast cancer patients and whether the associations differ according to radiotherapy. Using a prospective cohort of 1348 postmenopausal breast cancer patients, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for 109 single nucleotide polymorphisms (SNPs) using Cox proportional hazards regression. Validation of results was attempted using two Scandinavian studies. Eleven SNPs in MT2A, NFE2L2, NQO1, PRDX1, and PRDX6 were significantly associated with overall mortality after a median follow-up of 5.7 years. Three SNPs in NQO1 (rs2917667) and in PRDX6 (rs7314, rs4916362) were consistently associated with increased risk of dying across all three study populations (pooled: HRNQO1_rs2917667 1.20, 95% CI 1.00-1.44, p = 0.051; HRPRDX6_rs7314 1.16, 95% CI 1.00-1.35, p = 0.056, HRPRDX6_rs4916362 1.14 95% CI 1.00-1.32, p = 0.062). Potential effect modification by radiotherapy was found for CAT_rs769218. In conclusion, genetic variants in NQO1 and PRDX6 may modify breast cancer prognosis.
我们评估了 22 个与氧化应激相关的基因中的变异是否与乳腺癌患者的死亡率相关，以及这些关联是否因放疗而不同。我们使用了一个前瞻性队列的 1348 例绝经后乳腺癌患者，使用 Cox 比例风险回归估计了 109 个单核苷酸多态性 (SNP) 的危险比 (HR) 和 95%置信区间 (CI)。我们试图使用两个斯堪的纳维亚研究来验证结果。在中位随访 5.7 年后，MT2A、NFE2L2、NQO1、PRDX1 和 PRDX6 中的 11 个 SNP 与总死亡率显著相关。NQO1(rs2917667)和 PRDX6(rs7314, rs4916362)中的 3 个 SNP 在所有三个研究人群中均与死亡风险增加相关(汇总: HRNQO1_rs2917667 1.20, 95%CI 1.00-1.44, p = 0.051; HRPRDX6_rs7314 1.16, 95%CI 1.00-1.35, p = 0.056, HRPRDX6_rs4916362 1.14 95%CI 1.00-1.32, p = 0.062)。我们发现 CAT_rs769218 存在潜在的放疗效应修饰作用。总之，NQO1 和 PRDX6 中的遗传变异可能会改变乳腺癌的预后。
