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Leptin and leptin receptor genes in relation to premenopausal breast cancer incidence and grade in Caucasian women

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Abstract

Body mass is inversely related to breast cancer risk among premenopausal women. Leptin, an essential cytokine regulating food intake, energy expenditure, glucose, and fat metabolism may be part of the mechanistic pathway. We investigated 50 tagging and candidate SNPs in the leptin (LEP) and leptin receptor (LEPR) genes for associations with premenopausal breast cancer incidence using 405 cases and 810 controls nested within the Nurses’ Health Study II. We also examined associations between these SNPs and circulating leptin (among 910 women) and breast cancer grade (among 267 patients). Permutation tests were performed to adjust for multiple testing. We did not detect a significant association between SNPs in the LEP or LEPR gene and either breast cancer incidence or plasma leptin levels. Among cases, 14 SNPs of the LEPR gene were significantly associated with cancer grade, and rs1137101 (Q223R) survived multiple testing adjustment (adjusted P = 0.04). The G carriers of rs1137101 were more likely to have poorly differentiated than well-differentiated cancers. Our data suggest that common genetic variation in the LEP or LEPR gene has no strong association with premenopausal breast cancer risk. The LEPR gene might be associated with breast cancer grade.

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Acknowledgments

We thank Holly Harris for sharing references, Patrice Soule for assistance in manuscript editing, Hardeep Ranu, Carolyn Guo, Jiali Han, and Genevieve Monsees for help with checking genotype QC. This project was supported by Public Health Research Grant 1R01CA114326 from the National Cancer Institute, National Institutes of Public Health (to KBM.). The Nurses’ Health Study II is supported by Public Health Research Grant R01CA50385 from the National Cancer Institute, NIH (to Walter C. Willett). Fangyi Gu was supported by the Harvey Finberg fellowship and U01 CA098233. Megan Rice was supported by cancer training grant T32 CA09001.

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The authors of this manuscript report no conflict of interest.

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Authors and Affiliations

  1. Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA

    Fangyi Gu & Peter Kraft

  2. Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA

    Fangyi Gu, Peter Kraft & Karin B. Michels

  3. Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Megan Rice & Karin B. Michels

  4. Department of Obstetrics, Gynecology and Reproductive Biology, Obstetrics and Gynecology Epidemiology Center, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA, 02115, USA

    Karin B. Michels

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  1. Fangyi Gu
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  2. Peter Kraft
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Correspondence to Karin B. Michels.

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Gu, F., Kraft, P., Rice, M. et al. Leptin and leptin receptor genes in relation to premenopausal breast cancer incidence and grade in Caucasian women. Breast Cancer Res Treat 131, 17–25 (2012). https://doi.org/10.1007/s10549-011-1778-6

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  • DOI: https://doi.org/10.1007/s10549-011-1778-6

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