Polymorphisms in base excision repair genes: Breast cancer risk and individual radiosensitivity

Abstract

Breast cancer (BC) is the most common cancer among women worldwide. The aetiology and carcinogenesis of BC are not clearly defined, although genetic, hormonal, lifestyle and environmental risk factors have been established. The most common treatment for BC includes breast-conserving surgery followed by a standard radiotherapy (RT) regimen. However, radiation hypersensitivity and the occurrence of RT-induced toxicity in normal tissue may affect patients' treatment. The role of DNA repair in cancer has been extensively investigated, and an impaired DNA damage response may increase the risk of BC and individual radiosensitivity. Single nucleotide polymorphisms (SNPs) in DNA repair genes may alter protein function and modulate DNA repair efficiency, influencing the development of various cancers, including BC. SNPs in DNA repair genes have also been studied as potential predictive factors for the risk of RT-induced side effects. Here, we review the literature on the association between SNPs in base excision repair (BER) genes and BC risk. We focused on X-ray repair cross complementing group 1 (XRCC1 ), which plays a key role in BER, and on 8-oxoguanine DNA glycosylase 1, apurinic/apyrimidinic endonuclease 1 and poly (ADP-ribose) polymerase-1, which encode three important BER enzymes that interact with XRCC1. Although no association between SNPs and radiation toxicity has been validated thus far, we also report published studies on XRCC1 SNPs and variants in other BER genes and RT-induced side effects in BC patients, emphasising that large well-designed studies are needed to determine the genetic components of individual radiosensitivity.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Breast cancer; Polymorphisms; Base excision repair; Susceptibility; Radiosensitivity Core tip: Single nucleotide polymorphisms (SNPs) in DNA repair genes may modulate DNA repair efficiency, influencing the development of various cancers, including breast cancer (BC). SNPs in DNA repair genes have also been studied as predictors for the risk of radiotherapy-induced side effects. We reviewed the literature on the association between SNPs in base excision repair (BER) genes and BC risk. We focused on X-ray repair cross complementing group 1, 8-oxoguanine DNA glycosylase 1, apurinic/apyrimidinic endonuclease 1 and poly (ADP-ribose) polymerase-1, which encode four important BER proteins. We also report published studies on SNPs in BER genes and individual radiosensitivity in BC patients.

Polymorphisms in X-Ray Repair Cross-Complementing Group 1 Gene: Haplotypes, Breast Cancer Risk and Individual Radiosensitivity

“…In particular, Arg399Gln SNP, the most common variant in the XRCC1 gene, is an important polymorphism related to sporadic breast cancer susceptibility. Nevertheless, literature data showed a weak association of this SNP with BC risk, that is stronger only within some ethnicities [25]. In general, the effect of SNPs on the occurrence of breast cancer and other tumour types is usually only slightly statistically significant.…”

Impact of single-nucleotide polymorphisms on radiation pneumonitis in cancer patients

“…The genetic variants of DNA repair-related genes may affect the capacity of the DNA repair pathways. Insufficient DNA repair capacity leads to increased DNA damage and high tissue radiosensitivity, resulting in severe radiation-related complications (26,27).…”

Low-intensity red and infrared lasers affect mRNA expression of DNA nucleotide excision repair in skin and muscle tissue

“…These strategies include the base excision and nucleotide excision DNA repair pathways. Base excision repair acts on single strand breaks, oxidized bases, and few bulky adducts [15,16], induced by endogenous free radicals or from exogenous exposure to genotoxic agents [17]. Previous data demonstrated that the expression of messenger RNA (mRNA) related to base excision repair is altered in biological tissues exposed to low-intensity red [18] and infrared [19,20] lasers.…”