The role of DNA repair capacity in lung cancer risk among never-smokers: A systematic review of epidemiologic studies

Abstract Introduction While heavy smoking remains the predominant risk factor for lung cancer, 10–25% of lung cancers occur among never-smokers. Current lung screening practices do not include light and never-smokers and identifying those at increased risk due to underlying susceptibility is a priority for future cancer prevention. The accumulation of DNA damage due to suboptimal DNA repair capacity has been suggested to play an important role in lung carcinogenesis, particularly among never-smokers. Methods The objective of this review was to synthesize the epidemiologic literature on the role of DNA repair capacity and lung cancer risk among never-smokers. A systematic literature search was conducted using the MEDLINE database. In total, 67 studies met eligibility criteria and were included in this review. Findings Suboptimal DNA repair capacity and some DNA repair gene variants have been implicated as risk factors for lung cancer among never-smokers. A number of high-risk variants have been identified for genes in the base excision ( OGG1 , XRCC1 ), nucleotide excision (ERCC3, XPC, XPD ), mismatch (AGT, MLH1 , MSH2 ), and double-strand break ( ATM , ERCC1 , NSB1 , POLδ1 , RAD54B, RAD9 ) repair pathways. Susceptibility to DNA damage due to poor DNA repair capacity may increase the deleterious effect of known carcinogens (e.g. second-hand smoke). Conclusions Differential DNA repair capacity and DNA repair gene variation may explain some of the lung cancer risk among never-smokers. The number of studies to date are limited and many studies suffer from small sample size and there has been limited validation of findings. Methodological issues including tissue selection and standardizing lab techniques remain as barriers for evaluating DNA repair in population-based studies.