title: APEX1 Asp148Glu gene polymorphism is a risk factor for lung cancer in relation to smoking in Japanese.
abstract: DNA repair enzymes play an important role in the development of various kinds of cancer. We here analyzed associations of XPD Lys751Gln, APEX1 Asp148Glu, XRCC1 Arg399Gln, and XRCC3 Thr241Met gene polymorphisms in DNA repair pathways in relation to the risk of lung cancer using PCR-RFLP. The study involved 104 lung cancer patients and 120 non-cancer controls divided into non-smokers and smokers. We found a statistically significant interaction between APEX1 Asp148Glu and the risk for lung cancer (adjusted OR 2.78, 95% CI 1.58-4.90, p=0.0004), of both adenocarcinoma (adjusted OR 2.24, 95%CI 1.18-4.25, p=0.014) and squamous cell carcinoma (adjusted OR 4.75, 95%CI 1.79-12.6, p=0.002) types. XRCC1 Arg399Gln showed a borderline significant association with adenocarcinoma (adjusted OR 1.89, 95%CI 1.00-3.57, p=0.051). The combined effect of smoking and presence of the APEX1 Asp148Glu demonstrated a significant association with risk of lung cancer (adjusted OR 3.61, 95% CI 1.74-7.50, p=0.001). The XPD Lys751Gln and XRCC3 Thr241Met genotypes displayed no statistically significant risk. Our findings suggest that the APEX1 Asp148Glu is associated with increased risk for primary lung cancer in Japanese individuals partaking in smoking.
authors.affiliation: Faculty of Health Sciences, Kobe University Graduate School of Health Sciences, Kobe, Japan. osawak@kobe-u.ac.jp
authors.forename: Kayo
authors.initials: K
authors.lastname: Osawa
authors.forename: Aiko
authors.initials: A
authors.lastname: Miyaishi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Uchino
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Osawa
authors.forename: Natsuko
authors.initials: N
authors.lastname: Inoue
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakarai
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Tsutou
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kido
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tsubota
authors.forename: Juro
authors.initials: J
authors.lastname: Takahashi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; C497292:ERCC2 protein, human