title: Combined COMT and GST genotypes and hormone replacement therapy associated breast cancer risk.
abstract: Our previous studies suggested that both COMT and GST genotypes might modify individual breast cancer risk. Here, we extended the studies to examine the potential combined effect of these genotypes in susceptibility to breast cancer. Our study population consisted of 483 Finnish breast cancer cases and 482 population control subjects. The odds ratios (ORs) and (95%) confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected confounding factors. No significant increase in the overall breast cancer risk was seen for any combinations of the studied genotypes. However, a substantially increased risk of breast cancer was seen for women who had used hormone replacement therapy (HRT) and simultaneously carried the COMT-L allele containing genotypes and either the GSTP1 Ile/Ile genotype (OR 4.10, 95% CI 1.24-13.6) or the GSTT1 null genotype (OR 4.19, 95% CI 1.30-13.5). These associations appeared to be mainly attributable to long-term users of HRT; the respective ORs were 7.00 (95% CI 1.21-40.6) and 8.36 (95% CI 1.44-49.0) among the users of HRT of more than 30 months. In addition, the combination of COMT-L allele containing genotypes with the GSTM1 null genotype posed a remarkably increased risk (OR 9.10, 95% CI 1.84-45.0) of breast cancer in this study group. These results suggest that the use of HRT could substantially increase the risk of breast cancer among women with specific combinations of the at-risk genotypes of COMT and GST genes.
authors.affiliation: Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Katja
authors.initials: K
authors.lastname: Mitrunen
authors.forename: Vesa
authors.initials: V
authors.lastname: Kataja
authors.forename: Matti
authors.initials: M
authors.lastname: Eskelinen
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.forename: Simone
authors.initials: S
authors.lastname: Benhamou
authors.forename: Harri
authors.initials: H
authors.lastname: Vainio
authors.forename: Matti
authors.initials: M
authors.lastname: Uusitupa
authors.forename: Ari
authors.initials: A
authors.lastname: Hirvonen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D002394:Catechol O-Methyltransferase; D005982:Glutathione Transferase