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Energy homeostasis genes and breast cancer risk: The influence of ancestry, body size, and menopausal status, the breast cancer health disparities study
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Details:
  • Pubmed ID:
    26395295
  • Pubmed Central ID:
    PMC4679560
  • Funding:
    CA77305/CA/NCI NIH HHS/United States
    R01 CA63446/CA/NCI NIH HHS/United States
    HHSN261201000036C/PHS HHS/United States
    CA078682/CA/NCI NIH HHS/United States
    R01 CA078552/CA/NCI NIH HHS/United States
    R01 CA078762/CA/NCI NIH HHS/United States
    U58 DP000807/DP/NCCDPHP CDC HHS/United States
    R01 CA078802/CA/NCI NIH HHS/United States
    R01 CA078682/CA/NCI NIH HHS/United States
    R01 CA140002/CA/NCI NIH HHS/United States
    HHSN261201000036/CA/NCI NIH HHS/United States
    CA078552/CA/NCI NIH HHS/United States
    N01-PC-67000/PC/NCI NIH HHS/United States
    CA14002/CA/NCI NIH HHS/United States
    CA078762/CA/NCI NIH HHS/United States
    #1U58 DP000807-01/DP/NCCDPHP CDC HHS/United States
    CA63446/CA/NCI NIH HHS/United States
    CA078802/CA/NCI NIH HHS/United States
  • Document Type:
  • Collection(s):
  • Description:
    Background

    Obesity and breast cancer risk is multifaceted and genes associated with energy homeostasis may modify this relationship.

    Methods

    We evaluated 10 genes that have been associated with obesity and energy homeostasis to determine their association with breast cancer risk in Hispanic/Native American (2111 cases, 2597 controls) and non-Hispanic white (1481 cases, 1585 controls) women.

    Results

    Cholecystokinin (CCK) rs747455 and proopiomelanocortin (POMC) rs6713532 and rs7565877 (for low Indigenous American (IA) ancestry); CCK rs8192472 and neuropeptide Y (NYP) rs16141 and rs14129 (intermediate IA ancestry); and leptin receptor (LEPR) rs11585329 (high IA ancestry) were strongly associated with multiple indicators of body size. There were no significant associations with breast cancer risk between genes and SNPs overall. However, LEPR was significantly associated with breast cancer risk among women with low IA ancestry (PARTP = 0.024); POMC was significantly associated with breast cancer risk among women with intermediate (PARTP = 0.015) and high (PARTP = 0.012) IA ancestry. The overall pathway was statistically significant for pre-menopausal women with low IA ancestry (PARTP = 0.05), as was cocaine and amphetamine regulated transcript protein (CARTPT) (PARTP = 0.014) and ghrelin (GHRL) (PARTP = 0.007). POMC was significantly associated with breast cancer risk among post-menopausal women with higher IA ancestry (PARTP = 0.005). Three SNPs in LEPR (rs6704167, rs17412175, and rs7626141), and adiponectin (ADIPOQ); rs822391) showed significant 4-way interactions (GxExMenopausexAncestry) for multiple indicators of body size among pre-menopausal women.

    Conclusions

    Energy homeostasis genes were associated with breast cancer risk; menopausal status, body size, and genetic ancestry influenced this relationship.