Polymorphisms in three base excision repair genes and breast cancer risk in Thai women.
DNA repair plays an important role in tumor development. The base excision repair (BER) pathway mainly removes DNA damage caused by ionizing radiation and reactive oxidative species. Here, we examined possible associations between polymorphisms in three important BER genes (OGG1 Ser326Cys, APEX1 Asp148Glu, XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln) and breast cancer incidence in Thai women. The study population consisted of 507 breast cancer cases and 425 controls. Odds ratios (OR) were adjusted by multivariate logistic regression analysis for age, body mass index, age at menarche, family history of breast cancer, menopausal status, reproduction parameters, use of contraceptives, tobacco smoking, involuntary tobacco smoking, alcohol drinking, and education. For homozygous carriers of the Glu allele in APEX1, a significant protective effect was found when compared to Asp/Asp carriers (odds ratio (OR) = 0.60, 95% confidence interval (CI) = 0.38-0.94). Subgroup analysis based on menopausal status revealed increased breast cancer risk in postmenopausal women and OGG1 (OR = 2.05, 95% CI 1.14-3.69). Reconstructed diplotypes for XRCC1 showed that CGA/CGA carriers had an increased risk of breast cancer compared with carriers of the wild type diplotype CGG/CGG (OR = 2.56, 95% CI 1.28-5.15). When the joint effects of XRCC1, APEX1 and OGG1 polymorphisms were evaluated, individuals homozygous for two or three risk alleles were at increased risk (OR = 1.88, 95% CI 1.26-2.82). In conclusion, our data suggest that Thai women with a certain XRCC1 diplotype or homozygous for two or three variant alleles of XRCC1, OGG1, and APEX1 are likely to have an increased susceptibility to breast cancer.
Sangrajrang
Suleeporn
S
Research Division, National Cancer Institute, Bangkok, 10400, Thailand. sulee@health.moph.go.th
Schmezer
Peter
P
Burkholder
Iris
I
Waas
Peter
P
Boffetta
Paolo
P
Brennan
Paul
P
Bartsch
Helmut
H
Wiangnon
Surapon
S
Popanda
Odilia
O
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D045647:DNA Glycosylases / 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; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase