Abstract
BackgroundGenetic polymorphisms of DNA repair enzymes in the base excision repair (BER) pathway, may lead to genetic instability and lung cancer carcinogenesis. We investigated the interactions among the gene polymorphisms in DNA repair genes and lung cancer.MethodsWe analyzed associations among OGG1 Ser326Cys and MUTYH Gln324His gene polymorphisms in relation to lung cancer risk using PCR-RFLP. The study involved 108 lung cancer patients and 121 non-cancer controls divided into non-smokers, smokers according to pack-years smoked in Japanese.ResultsThe results showed that the MUTYH His/His genotype compared with Gln/Gln genotype showed an increased risk for lung cancer (adjusted odds ratio [OR] 3.03, confidence interval [95%CI], 1.31–7.00, p = 0.010), whereas there was no significant increase for the Gln/His genotype (adjusted OR 1.35, 95%CI 0.70–2.61, p = 0.376). The MUTYH His/His genotype was at a borderline increased risk for both adenocarcinoma and squamous cell carcinoma (adjusted OR 2.50, 95%CI 0.95–6.62, p = 0.065 for adenocarcinoma; adjusted OR 3.20, 95%CI 0.89–11.49, p = 0.075 for squamous cell carcinoma, respectively). However, the OGG1 Ser/Cys or Cys/Cys genotypes compared with the Ser/Ser genotype did not have significantly increased risk for lung cancer, containing either adenocarcinoma or squamous cell carcinoma. The joint effect of tobacco exposure and the MUTYH His/His genotype compared with the Gln/Gln genotype showed a significant association with lung cancer risk in smokers, and there was not significantly increased in non-smokers (adjusted OR 3.82, 95%CI 1.22–12.00, p = 0.022 for smokers; adjusted OR 2.60, 95%CI 0.60–11.25, p = 0.200 for non-smokers, respectively). The effect of tobacco exposure and the OGG1 Ser326Cys showed also no significant risk for lung cancer.ConclusionOur findings suggest that the MUTYH Gln324His polymorphism appear to play an important role in modifying the risk for lung cancer in the Japanese population.
Highlights
Genetic polymorphisms of DNA repair enzymes in the base excision repair (BER) pathway, may lead to genetic instability and lung cancer carcinogenesis
The crude and adjusted ORs for the mutY homolog (MUTYH) His/His genotype compared with Gln/ Gln genotype showed a increased risk for lung cancer, whereas there was no significant increase for the Gln/His genotype
The crude and adjusted ORs for the oxo-guanine glycosylase-1 (OGG1) Ser/Cys or Cys/Cys genotypes compared with the Ser/Ser genotype were not significant for adenocarcinoma and squamous cell carcinoma
Summary
Genetic polymorphisms of DNA repair enzymes in the base excision repair (BER) pathway, may lead to genetic instability and lung cancer carcinogenesis. DNA damage induced by these carcinogens or by endogenous metabolic processes can be converted into gene mutations. In a hospital-based patient-control study, we reported that genetic polymorphisms of NAT2 and CYP1A2 in metabolic processes contributed to lung cancer susceptibility depending on smoking status in Japanese population [1]. The base excision repair (BER) pathway, one of the DNA repair pathways, plays an important role in repairing the DNA damage resulting from chemical alterations of a single base, such as methylated, oxidized, or reduced bases [3]. The most stable product of oxidative DNA damage, 8-oxo-7, 8-dihydro-2'deoxyguanosine (8-oxoG), causes G:C→T:A transversions, because 8-oxoG pairs with adenine as well as cytosine [4]. The proteins that repair these mutations are 8-oxo-guanine glycosylase-1 (OGG1), which is involved in direct repair by 8-oxoG DNA glycosylase, and mutY homolog (MUTYH), which is involved in repair of adenine to 8-oxoG mismatch or that of guanine to 1,2-dihydro-2-oxoadenine (2-OH-A) mismatch due to its glycosylase activity [5,6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
