Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, China.
Cancer Med. 2021 Apr;10(8):2752-2762. doi: 10.1002/cam4.3847. Epub 2021 Mar 18.
X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction.
The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models.
XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (p = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (p = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (p = 0.0497). However, these interactions became insignificant after Bonferroni correction.
XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.
X 射线修复交叉互补基因 5（XRCC5）和 6（XRCC6）对于 DNA 修复至关重要。很少有研究评估它们与乳腺癌风险的关系，相关的基因-环境相互作用仍知之甚少。本研究旨在确定 XRCC5/6 多态性对乳腺癌风险的影响，以及它们与吸烟、饮酒和睡眠满意度的相互作用。
本研究纳入了 1039 例乳腺癌患者和 1040 例对照。对 XRCC5 的 4 个单核苷酸多态性和 XRCC6 的 2 个单核苷酸多态性进行了基因分型。通过问卷收集了吸烟、饮酒和睡眠满意度的信息。采用非条件 logistic 回归模型评估比值比（OR）及其相关 95%置信区间（95%CI）。采用具有乘法交互作用模型的 logistic 回归分析基因-环境相互作用。
经过 Bonferroni 校正后，XRCC5 rs16855458 的共显性（p=0.003）和显性（CA+AA 与 CC，OR=1.29，95%CI=1.07-1.56，p=0.008）遗传模型与乳腺癌风险增加相关。XRCC6 rs2267437 的 CG+GG 基因型与雌激素受体阴性/孕激素受体阴性（ER-/PR-）乳腺癌风险增加相关（CG+GG 与 CC：OR=1.54，95%CI=1.12-2.13，p=0.008）。此外，XRCC5 rs16855458 与饮酒之间存在拮抗交互作用（p=0.017），XRCC6 rs2267437 与睡眠满意度之间存在协同交互作用（p=0.0497），与乳腺癌风险相关。然而，经过 Bonferroni 校正后，这些相互作用变得不显著。
XRCC5 rs16855458 与乳腺癌风险相关，XRCC6 rs2267437 与 ER-/PR-乳腺癌风险相关。XRCC5 和 XRCC6 多态性与乳腺癌风险相关的可能性分别取决于饮酒和睡眠满意度，值得进一步研究。
