title: Genetic polymorphisms in APE1 are associated with renal cell carcinoma risk in a Chinese population.
abstract: Apurinic/apyrimidinic endonuclease 1 (APE1) is a DNA repair protein, which plays important roles in the base excision repair (BER) pathway. Genetic variations of APE1 have been shown to influence an individual's susceptibility to carcinogenesis. We hypothesized the genetic polymorphisms of APE1 are associated with the risk of renal cell carcinoma (RCC). In a case-control study of 612 RCC patients and 632 age and sex matched healthy controls, we genotyped two APE1 functional polymorphisms (-656 T>G, rs1760944 and 1349 T>G, rs1130409) and assessed their associations with risk of RCC. We found that, compared with 1349 TT/TG genotypes, the variant genotype 1349 GG had a significantly increased RCC risk [adjusted odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.10-1.95], particularly among subgroups of BMI > 23 kg/m(2) (OR = 1.54, 95% CI = 1.06-2.22), male (OR = 1.70, 95% CI = 1.17-2.46), never smokers (OR = 1.56, 95% CI = 1.11-2.21), light smokers (OR = 2.01, 95%CI = 1.02-3.95), and drinkers (OR = 2.00, 95% CI = 1.13-3.54). Furthermore, the polymorphism was significantly associated with risk of developing localized stage RCC. No altered RCC risk was associated with the -656 T>G polymorphism, but we found individuals who were homozygous for both risk alleles of the two SNPs had a 2.17-fold increased risk for RCC, compared to individuals with 0 risk alleles. Our results suggest that polymorphisms of APE1 may confer susceptibility to RCC.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cao
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Meng
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Ju
authors.forename: Qi
authors.initials: Q
authors.lastname: Ding
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Pu
authors.initials: P
authors.lastname: Li
authors.forename: Jiawei
authors.initials: J
authors.lastname: Chen
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D016022:Case-Control Studies; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase