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World J Clin Oncol. Dec 10, 2014; 5(5): 874-882
Published online Dec 10, 2014. doi: 10.5306/wjco.v5.i5.874
Polymorphisms in base excision repair genes: Breast cancer risk and individual radiosensitivity
Clarice Patrono, Silvia Sterpone, Antonella Testa, Renata Cozzi
Clarice Patrono, Antonella Testa, Technical Unit of Radiation Biology and Human Health, Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), 00123 Rome, Italy
Silvia Sterpone, Renata Cozzi, Department of Science, University “Roma TRE”, 00146 Rome, Italy
Author contributions: Patrono C and Cozzi R organised and structured the review; Patrono C wrote the paper; Sterpone S, Testa A and Cozzi R critically revised the manuscript; all authors approved the final version.
Correspondence to: Renata Cozzi, Professor, Department of Science, University “Roma TRE”, Viale G. Marconi 446, 00146 Rome, Italy. renata.cozzi@uniroma3.it
Telephone: +39-6-57336330
Received: December 29, 2013
Revised: April 3, 2014
Accepted: April 17, 2014
Published online: December 10, 2014
Processing time: 347 Days and 11.9 Hours
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.

Keywords: 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.