XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi-center study

Cancer Med. 2021 Apr;10(8):2752-2762. doi: 10.1002/cam4.3847. Epub 2021 Mar 18.

Abstract

Background: 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.

Methods: 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.

Results: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (ptrend = 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 (pinteraction = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (pinteraction = 0.0497). However, these interactions became insignificant after Bonferroni correction.

Conclusion: 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.

Keywords: XRCC5; XRCC6; alcohol consumption; breast cancer; gene-environment interaction; sleep satisfaction; smoking.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alcohol Drinking / genetics*
  • Asian People / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Ku Autoantigen / genetics*
  • Middle Aged
  • Personal Satisfaction
  • Polymorphism, Single Nucleotide
  • Sleep / physiology
  • Smoking / genetics*

Substances

  • XRCC5 protein, human
  • Xrcc6 protein, human
  • Ku Autoantigen