title: IGHMBP2 Thr671Ala polymorphism might be a modifier for the effects of cigarette smoking and PAH-DNA adducts to breast cancer risk.
abstract: Laboratory and bioinformatics studies have suggested that immunoglobulin mu-binding protein 2 (IGHMBP2) is involved in DNA repair, replication and recombination. Using 1067 cases and 1110 controls from a population-based case-control study, we sought to clarify the potential role of the IGHMBP2 Thr671Ala polymorphism (A to G substitution) alone and as a modifier of the effects for cigarette smoking and PAH-DNA adducts on breast cancer risk. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, there was no significant association between the IGHMBP2 variant-G allele and breast cancer risk (OR = 1.1, 95% CI = 0.9-1.3). Increased risk was found among women who had detectable PAH-DNA adducts and carried at least one variant-G allele (OR = 1.4, 95% CI = 1.0-1.8, p for trend = 0.01) compared to women carrying the wild-type AA genotype and with non-detectable adducts. Smokers carrying the IGHMBP2 variant-G allele had no significant increased breast cancer risk compared with non-smoking women with the AA genotype. Heavy smokers (>31 pack years) had a statistically significant association with breast cancer risk (OR=2.0, 95% CI=1.2-3.3) relative to nonsmokers with the AA genotype though the magnitude of association was not different than heavy smokers (> 31 pack years) with the AA genotype (OR=1.6, 95% CI=0.9-2.6). Overall our study observes only modestly higher effect estimates for PAH-DNA adduct exposure and cigarette smoking among those with the high-risk genotype, but these differences are not statistically significant. Additional studies focused on the biological function of the variant-G allele and interactions with other genetic polymorphisms are necessary to confirm our findings.
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA. js2182@columbia.edu
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Terry
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.forename: Susan L
authors.initials: SL
authors.lastname: Teitelbaum
authors.forename: Sybil M
authors.initials: SM
authors.lastname: Eng
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Sagiv
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Neugut
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
mesh_terms: D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018736:DNA Adducts / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry*; D011110:Polymorphism, Genetic; D012306:Risk; D012907:Smoking; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018736:DNA Adducts; D004268:DNA-Binding Proteins; C489892:IGHMBP2 protein, human; D011084:Polycyclic Aromatic Hydrocarbons; D014157:Transcription Factors; C095911:polycyclic aromatic hydrocarbons-DNA adduct