Association Between Single Nucleotide Polymorphisms in DNA Polymerase Kappa Gene and Breast Cancer Risk in Chinese Han Population

Abstract

DNA polymerases are responsible for ensuring stability of the genome and avoiding genotoxicity caused by a variety of factors during DNA replication. Consequently, these proteins have been associated with an increased cancer risk. DNA polymerase kappa (POLK) is a specialized DNA polymerase involved in translesion DNA synthesis (TLS) that allows DNA synthesis over the damaged DNA. Recently, some studies investigated relationships between POLK polymorphisms and cancer risk, but the role of POLK genetic variants in breast cancer (BC) remains to be defined. In this study, we aimed to evaluate the effects of POLK polymorphisms on BC risk.We used the Sequenom MassARRAY method to genotype 3 single nucleotide polymorphisms (SNPs) in POLK (rs3213801, rs10077427, and rs5744533), in order to determine the genotypes of 560 BC patients and 583 controls. The association of genotypes and BC was assessed by computing the odds ratio (OR) and 95% confidence intervals (95% CIs) from logistic regression analyses.We found a statistically significant difference between patient and control groups in the POLK rs10077427 genotypic groups, excluding the recessive model. A positive correlation was also found between positive progesterone receptor (PR) status, higher Ki67 index, and rs10077427 polymorphism. For rs5744533 polymorphism, the codominant, dominant, and allele models frequencies were significantly higher in BC patients compared to healthy controls. Furthermore, our results indicated that rs5744533 SNP has a protective role in the postmenopausal women. However, we failed to find any associations between rs3213801 polymorphism and susceptibility to BC.Our results indicate that POLK polymorphisms may influence the risk of developing BC, and, because of this, may serve as a prognostic biomarker among Chinese women.

Polymorphisms in TIM-3 and breast cancer susceptibility in Chinese women: A case-control study

“…This case-control study included 560 patients with BC and 583 cancer-free controls, as we described previously [40, 41]. All participants were recruited without the restrictions of age.…”

Tobacco smoking and smoking-related DNA methylation are associated with the development of frailty among older adults

“…35 The corresponding genes POLK for cg05673882 and ALPP for cg23667432 are oncogenes that play roles in the formation of several age-related cancers, including breast, prostate, lung, and ovarian cancers. [36][37][38][39] The biologic functions of the remaining 3 loci within unassigned genome regions are not yet known, only locus cg01127300 has been disclosed as a potential epigenetic regulator of obesity, 40 one of the deficits of the frailty syndrome. 41 Interestingly, neither of the most strongly smoking-related CpG sites, cg05575921 (AHRR) or cg03636183 (F2RL3), 26 was identified to be related to the FI in the present study.…”

Six Germline Genetic Variations Impair the Translesion Synthesis Activity of Human DNA Polymerase κ

“…26–28 Mice lacking pol κ exhibit a spontaneous mutator phenotype in various tissues and reduced survival. 29 At present, no human disease linked to pol κ defect has been reported, but a haplotype and a noncoding single nucleotide polymorphism (SNP) of the POLK gene were negatively associated with lung cancer risk, 30 while two noncoding POLK SNPs were positively associated with breast cancer risk, 31 although specific mechanisms have not been revealed. Also, seven noncoding POLK SNPs were associated with platinum chemotherapy response, toxicity, or progression-free survival in non-small cell lung cancer patients.…”