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

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.

Using machine learning to identify gene interaction networks associated with breast cancer

“…This study sought to identify potential pathogenic genes associated with BC by constructing a BC gene interaction network. This study extended the results of prior studies [ 14 ] by not only assessing the effect of a single gene on BC but also the gene interaction network, providing new insight into how genetic factors impact complex human diseases. These results suggest that BMI and menopausal status may be risk factors for BC.…”

“…Low-grade systemic inflammation is one of the characteristics of obesity [ 38 ], and RETN is shown to exert pro-inflammatory properties by upregulating pro-inflammatory cytokines [ 39 ] through the NFκB signaling pathway [ 40 ] that lead to inflammation and tumorigenesis. Several studies have also linked XRCC6 with an increased risk of BC [ 14 , 41 , 42 ]. Interaction between XRCC6 genetic polymorphisms and reproductive risk factors is thought by some researchers to contribute to estrogen exposure, which results in double-strand breaks on BRCA1 and BRCA2 DNA and induces BC [ 41 ].…”

“…Several studies have identified the genomic region of PTPN1 as a quantitative trait locus (QTL) in obesity and diabetes mellitus [ 11 – 13 ]. XRCC5 and XRCC6 SNP genotyping revealed that XRCC5 rs16855458 was associated with BC, XRCC6 rs2267437 was associated with ER-/PR- BC risk, and there may be interactions with environmental factors [ 14 ]. However, current research has largely focused on the impact of a single SNP on disease, and potential SNP-SNP interactions remain less well studied.…”

Relationships between Maternal Folic Acid Supplementation and GATA4 Gene Polymorphisms in Patients with Non-Chromosomal Congenital Heart Disease: A Hospital-Based Case–Control Study in China

“…The occurrence of CHD might be caused by a combination of genetic variations and maternal lifestyle factors before or during pregnancy. Gene-environment interactions could be deterministic for CHD in individuals who were exposed to environmental risk factors [28]. Recent studies have suggested that the genes related to FA metabolism (i.e., MTHFR, MTRR, MTR, and CBS) might have gene-environment interactions that influence individual susceptibility to CHD [29,30].…”

Polymorphisms of DNA Repair Genes in Thyroid Cancer

“…We did not find any reports on the study of XRCC6 (Ku70) polymorphisms in the context of thyroid cancer risk. However, there are studies on other tumors [ 58 , 59 , 60 ].…”