OGG1 polymorphisms and breast cancer risk.
The role of oxidative stress in breast cancer risk is still unclear. OGG1 encodes an 8-oxoguanine DNA glycosylase/AP lyase that catalyzes the removal of 8-oxodeoxyguanosine from DNA. 8-Oxodeoxyguanosine, the most abundant lesion generated by oxidative stress, is highly mutagenic. Environmental sources of oxidative stress, such as alcohol consumption, cigarette smoking, high body mass index (BMI), and low fruits and vegetables intake, may modify the association of genetic polymorphisms with breast cancer risk. We investigated the association between three genetic polymorphisms in OGG1 (Ser(326)Cys, 7143A/G, and 11657A/G) and breast cancer risk among 1,058 cases and 1,102 controls participating in the Long Island Breast Cancer Study Project. No associations were observed between individual OGG1 polymorphisms, haplotypes, or diplotypes and breast cancer. The association between having at least one variant allele and breast cancer risk was stronger among moderate alcohol drinkers for Ser(326)Cys [odds ratio (OR), 1.82; 95% confidence interval (95% CI), 1.06-3.10] relative to nondrinkers with the wild-type genotype and among those with higher BMI for 7143A/G (OR, 1.47; 95% CI, 1.10-1.96) and for 11657A/G (OR, 1.41; 95% CI, 1.05-1.88), relative to women with BMI < 25 kg/m(2) and the wild-type genotype. However, the patterns were not seen for all three single nucleotide polymorphisms (SNP) nor were there any clear allele dose associations; only one interaction was statistically significant, assuming a multiplicative model (11657A/G, P(interaction) = 0.04). In summary, although we found some differences between the three OGG1 SNPs and breast cancer risk among moderate alcohol drinkers and women with higher BMI, replication of these results is needed to rule out spurious findings. In addition, data on functionality of these polymorphisms are crucial to understand if these modest differences are important.
Rossner
Pavel
P
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA. prossner@biomed.cas.cz
Terry
Mary Beth
MB
Gammon
Marilie D
MD
Zhang
Fang Fang
FF
Teitelbaum
Susan L
SL
Eng
Sybil M
SM
Sagiv
Sharon K
SK
Gaudet
Mia M
MM
Neugut
Alfred I
AI
Santella
Regina M
RM
D000428:Alcohol Drinking / Q000009:adverse effects; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D006801:Humans; D009765:Obesity / Q000150:complications; D016017:Odds Ratio; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human