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

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 uan, MD, Meng W g Liu, MD, MS, and Xi-Jing Wang, MD 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. (Medicine 95(2):e2466) Abbreviations: BC = breast cancer, CI = confidence interval, DSB = double strand break, OR = odds ratio, POLK = DNA polymerase kappa, PR = progesterone receptor, SNP = single nucleotide polymorphism, TLS = translesion DNA synthesis. INTRODUCTION B reast cancer (BC) is the 2nd most common type of cancer in the world and the leading cancer type among women, with an estimated 1.67 million new cases diagnosed in 2012. Multiple factors, both genetic and nongenetic, are involved in its pathogenesis. Approximately 5% to 10% of all BC cases are considered to be hereditary. Previous studies showed that impaired DNA repair plays an important role in genetic instability and cancer development, especially during breast tumorigenesis. DNA molecule is constantly subjected to a wide variety of DNA damaging agents, either environmental (UV light, ionizing radiation, chemical poisons, and drugs) or endogenous (reactive oxygen species by products of routine metabolic processes) ones. DNA double-strand breaks (DSBs) are considered to be one of the most lethal forms of DNA damage, because a single unrepaired DSB results in a lethal cell growth arrest and an inhibition of cell cycle progression. An efficient DNA damage response signaling network commonly includes DNA repair pathways and tolerance mechanisms that, with cell cycle checkpoints, work together to ensure the integrity of the genome. DNA repair pathways include DNA strand break repair, mismatch repair, nucleotide excision repair, base excision repair, and ribonucleotide excision repair mechanisms. Loss of 1 DNA repair pathway constituent may be compensated for by an increase in the activity of different components of the same or other pathways. However, following major DSB lesions, these repair mechanisms are not effective in repairing DNA damage, because DNA molecule cannot serve as a ion of the replication fork is impaired. esis (TLS) can bypass damaged nucleoA replication, and this process is carried www.md-journal.com | 1 out by specialized DNA polymerases (b, i, k). Several recent studies reported possible association of DNA polymerase k (POLK) with different types of cancer, for example, prostate cancer and nonsmall cell lung cancer. Until now, the link between POLK polymorphisms and BC has not been established. Single nucleotide polymorphisms (SNPs) are thought to play an important role in genetic susceptibility to cancer. Numerous SNPs have been identified in the human POLK gene using sequence databases. We chose to investigate 3 POLK polymorphisms (rs3213801, rs10077427, and rs5744533) that are annotated in NCBI databases, but their association with BC risk was not previously determined. Herein, we conducted a case–control study to investigate this association in the Chinese Han population.