Breast Cancer Research and Treatment

, Volume 131, Issue 1, pp 17–25 | Cite as

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

  • Fangyi Gu
  • Peter Kraft
  • Megan Rice
  • Karin B. Michels


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.


Premenopausal Breast cancer Leptin Leptin receptor 


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Fangyi Gu
    • 1
    • 2
  • Peter Kraft
    • 1
    • 2
  • Megan Rice
    • 3
  • Karin B. Michels
    • 2
    • 3
    • 4
  1. 1.Program in Molecular and Genetic EpidemiologyHarvard School of Public HealthBostonUSA
  2. 2.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  3. 3.Channing Laboratory, Department of MedicineBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  4. 4.Department of Obstetrics, Gynecology and Reproductive Biology, Obstetrics and Gynecology Epidemiology CenterBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA

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