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Genetic polymorphisms of TGF-β1 & TNF-β and breast cancer risk

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Abstract

Objective. The proliferation of malignant breast epithelial cells is regulated by various stimuli including cytokines and growth factors, thus the variants of those genes may modify the breast cancer risk. To evaluate the potential influences of TGF-β1 T 29C and TNF-β A252G gene polymorphisms on breast cancer risk, a case–control study was conducted in Korea.

Methods. Histologically confirmed breast cancer cases (n = 560) and controls (n=509) with no previous history of cancer were recruited from three teaching hospitals in Seoul, Korea. Genotypes were determined by PCR-CTPP (polymerase chain reaction with confronting two-pair primers) method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression model adjusting for age, body mass index, education, parity, age at first full-term pregnancy, and family history of breast cancer.

Results. The TGF-β1 29C-allele containing genotypes posed an increased risk of breast cancer (OR=1.3, 95% CI=1.02–1.79), especially in postmenopausal women (OR=1.6, 95% CI=1.01–2.44). Similarly, the TNF-β 252G-allele containing genotypes posed an increased risk of postmenopausal breast cancer (OR=1.7, 95% CI=1.09–2.55). The risk of postmenopausal breast cancer increased in parallel with the number of the risk genotypes (p for trend <0.01). When data were stratified by the presumed non-genetic risk factors, TGF-β1 C-allele containing genotypes were found to increase breast cancer risk almost two-fold in postmenopausal women with greater than median body mass index (>22.8 kg/m2) (OR=1.9, 95% CI=1.04–3.37).

Conclusion. The results of this study therefore suggest that polymorphisms of TGF-β1 and TNF-β genes may modify individual susceptibility to breast cancer in Korean women.

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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, Seoul, 110-799, Korea

    Kyoung-Mu Lee, Keun-Young Yoo & Daehee Kang

  2. Department of Preventive Medicine, Konkuk University College of Medicine, 322 Danwol-Dong, Chungju, Chungcheongbuk-Do, 380-701, Korea

    Sue Kyung Park & Aesun Shin

  3. Department of Preventive Medicine, Biostatistics and Medical Decision Making, Nagoya Graduated School of Medicine, Nagoya, Japan

    Nobuyuki Hamajima

  4. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusaku, Nagoya, 464-8681, Japan

    Kazuo Tajima

  5. Department of Surgery, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-799, Korea

    Dong-Young Noh

  6. Department of Surgery, Asan Medical Center, Ulsan University College of Medicine, 388-1 Pungnab-Dong, Songpa-Gu, Seoul, 138-736, Korea

    Sei-Hyun Ahn

  7. Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, FIN-00250, Finland

    Ari Hirvonen

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  1. Kyoung-Mu Lee
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Correspondence to Daehee Kang.

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Lee, KM., Park, S.K., Hamajima, N. et al. Genetic polymorphisms of TGF-β1 & TNF-β and breast cancer risk. Breast Cancer Res Treat 90, 149–155 (2005). https://doi.org/10.1007/s10549-004-3859-2

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