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Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival

Breast Cancer Research and Treatment volume 120, pages 745–752 (2010)Cite this article

Abstract

Obesity is a strong risk factor for breast cancer in postmenopausal women and adverse prognostic indicator regardless of menopausal status. Leptin is an important regulator of adipose tissue mass and has been associated with tumor cell growth. Leptin exerts its effects through interaction with the leptin receptor (LEPR). We investigated whether genetic variations in the leptin (LEP) and LEPR genes are associated with risk of breast cancer, or once diagnosed, with survival. The polymorphisms LEP G-2548A and LEPR Q223R were characterized in population-based study consisting of mostly European-American women. The study examined 1,065 women diagnosed with first, primary invasive breast cancer between 1996 and 1997. Controls were 1,108 women frequency matched to the cases by 5-year age group. A modest increase in risk of developing breast cancer was associated with the LEP −2548AA genotype when compared to the LEP −2548GG genotype (age-adjusted OR = 1.30; 95% CI = 1.01–1.66). This association was stronger among postmenopausal women who were obese (OR = 1.86; 95% CI = 0.95–3.64) although the interaction was of borderline statistical significance (P = 0.07). We found no evidence of an association with polymorphisms of either LEP or LEPR in relation to all-cause or breast cancer-specific mortality among women with breast cancer (mean follow-up time = 66.7 months). The effects of these genotypes on breast cancer risk and mortality did not vary significantly when stratified by menopausal status. In summary, our results show that a common variant in LEP may be associated with the risk of developing breast cancer supporting the hypothesis that leptin is involved in breast carcinogenesis.

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Acknowledgments

For their valuable contributions, the authors thank: members of the Long Island Breast Cancer Network; the participating institutions; our NIH and NIEHS collaborators; members of the External Advisory Committee to the population-based case–control study. We also wish to acknowledge and thank the following LIBCSP collaborators for their contributions with various aspects of our study efforts including: Amanda Golembesky, Ph.D. and Julie Britton, Ph.D. This work is supported by the University of North Carolina Nutrition and Cancer Training grant NCI T32CA72319; National Cancer Institute and the National Institutes of Environmental Health and Sciences grant nos. UO1CA/ES66572, UO1CA66572, P50CA52283, P30ES09089, P30ES10126, and 5T32CA009330-25; and the Breast Cancer Research Fund.

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Affiliations

  1. Department of Nutrition, School of Public Health, University of North Carolina, CB# 7461, Chapel Hill, NC, 27599-7461, USA

    Rebecca J. Cleveland

  2. Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA

    Marilie D. Gammon

  3. Department of Environmental Health Sciences, Mailman School of Public Heath, Columbia University, New York, NY, USA

    Chang-Min Long & Regina M. Santella

  4. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Mia M. Gaudet

  5. Global Epidemiology, Safety, and Risk Management, Pfizer, Inc., New York, NY, USA

    Sybil M. Eng

  6. Department of Community and Preventive Medicine, Mt. Sinai School of Medicine, New York, NY, USA

    Susan L. Teitelbaum

  7. Department of Epidemiology, Mailman School of Public Heath, Columbia University, New York, NY, USA

    Alfred I. Neugut

Authors
  1. Rebecca J. Cleveland
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  2. Marilie D. Gammon
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  3. Chang-Min Long
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  4. Mia M. Gaudet
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  5. Sybil M. Eng
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  6. Susan L. Teitelbaum
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  7. Alfred I. Neugut
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  8. Regina M. Santella
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Correspondence to Rebecca J. Cleveland.

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Cleveland, R.J., Gammon, M.D., Long, CM. et al. Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival. Breast Cancer Res Treat 120, 745–752 (2010). https://doi.org/10.1007/s10549-009-0503-1

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  • DOI: https://doi.org/10.1007/s10549-009-0503-1

Keywords

  • Leptin
  • Leptin receptor
  • Polymorphism
  • Obesity
  • Breast cancer