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Combined effect of GSTM1, GSTT1, and COMT genotypes in individual

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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 andCOMT genotypes in human breast carcinogenesis.

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Authors and Affiliations

  1. Department of Preventive Medicine Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Korea

    Sue Kyung Park, Dong-seok Yim, In-mi Choi, Ji-yeob Choi & Keun-young Yoo

  2. Konkuk University, Institute of Medical Science, Korea

    Sue Kyung Park

  3. Kyung Hee University, Korea

    Kyung-sik Yoon

  4. Department of Surgery, Seoul National University College of Medicine, Korea

    Dong-young Noh

  5. Department of Surgery, Seoul National University College of Medicine, Korea

    Kuk-jin Choe

  6. Asan Medical Center, Korea

    Sei-hyun Ahn

  7. Department of Industrial Hygiene and Toxicology, Institute of Occupational Health, 28 Yongon-Dong Chongno-Gu, Finland

    Ari Hirvonen

  8. Department of Preventive Medicine, Konkuk University College of Medicine, Korea

    Daehee Kang

  9. Seoul National University, Cancer Research Institute, Korea

    Daehee Kang

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  1. Sue Kyung Park
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Park, S.K., Yim, Ds., Yoon, Ks. et al. Combined effect of GSTM1, GSTT1, and COMT genotypes in individual. Breast Cancer Res Treat 88, 55–62 (2004). https://doi.org/10.1007/s10549-004-0745-x

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  • DOI: https://doi.org/10.1007/s10549-004-0745-x

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