title: Combined effect of GSTM1, GSTT1, and COMT genotypes in individual breast cancer risk.
abstract: Our previous studies suggested that both catechol O-methyl transferase (COMT) and glutathione S-transferase (GST) M1 and T1 genotypes are associated with breast cancer risk. Here we extended the studies to evaluate the potential combined effect of these genotypes in individual breast cancer risk. Incident breast cancer cases (n = 202) and controls (n = 299) with no previous cancer were recruited from three teaching hospitals in Seoul in 1996-1999. Information on putative risk factors was collected by interviewed questionnaire. PCR-based methods were used for the genotyping analyses. Odds ratios (ORs) and 95% confidence (CIs) intervals were estimated by unconditional logistic regression after adjustment for known or suspected risk factors of breast cancer. Among pre-menopausal women the low activity associated (COMT *L) allele containing genotypes and the GSTM1 null genotype posed increased risks of breast cancer with ORs of 1.7 (95% CI = 1.0 - 2.8) and 1.7 (95% CI = 1.0-2.8), respectively. A marginally significant effect of GSTT1 null genotype was also observed when the total study population was considered (OR = 1.3, 95% CI = 1.0-2.1). When the combined genotype effects were examined, the concurrent lack of GSTM1 and GSTT1 genes posed a more than 2-fold risk of breast cancer (OR = 2.2, 95% CI = 1.2-3.9); this effect was mainly attributable in pre-menopausal women (OR = 3.2, 95% CI = 1.5-7.2). Moreover, the breast cancer risk increased in parallel with the number of COMT , GSTM1 , and GSTT1 at-risk genotypes (p for trend = 0.003). This association was particularly clear in pre-menopausal women among whom combination of all three high-risk genotypes posed a 4.1-fold breast cancer risk (95% CI = 1.4-12.7) compared with pre-menopausal women without at-risk genotypes (p for trend = 0.001). The trend was more pronounced in women with BMI greater than 22 kg/m2 (p for trend < 0.001) and high-risk status of parity factor (nulliparous or women with the first full term pregnancy at age of over 25-year-old) (p for trend = 0.013). These results suggest the combined effect between reproductive factors and GSTM1, GSTT1 and COMT genotypes in human breast carcinogenesis.
authors.affiliation: Department of Preventive Medicine Cancer Research Institute, Konkuk University College of Medicine, Chungju, Korea.
authors.forename: Sue Kyung
authors.initials: SK
authors.lastname: Park
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Yim
authors.forename: Kyung-Sik
authors.initials: KS
authors.lastname: Yoon
authors.forename: In-Mi
authors.initials: IM
authors.lastname: Choi
authors.forename: Ji-Yeob
authors.initials: JY
authors.lastname: Choi
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.forename: Kuk-Jin
authors.initials: KJ
authors.lastname: Choe
authors.forename: Sei-Hyun
authors.initials: SH
authors.lastname: Ahn
authors.forename: Ari
authors.initials: A
authors.lastname: Hirvonen
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017697:Premenopause; D012307:Risk Factors
chemical_list: D002394:Catechol O-Methyltransferase; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1