Energy homeostasis genes and survival after breast cancer diagnosis: The Breast Cancer Health Disparities Study
Published Date:Jan 2016
Source:Cancer Causes Control. 27(1):47-57.
Pubmed Central ID:PMC4833710
Funding:#1U58DP000807-01/DP/NCCDPHP CDC HHS/United States
CA078552/CA/NCI NIH HHS/United States
CA078682/CA/NCI NIH HHS/United States
CA078762/CA/NCI NIH HHS/United States
CA078802/CA/NCI NIH HHS/United States
CA14002/CA/NCI NIH HHS/United States
CA63446/CA/NCI NIH HHS/United States
CA77305/CA/NCI NIH HHS/United States
R01 CA063446/CA/NCI NIH HHS/United States
R01 CA078552/CA/NCI NIH HHS/United States
R01 CA078682/CA/NCI NIH HHS/United States
R01 CA078762/CA/NCI NIH HHS/United States
R01 CA078802/CA/NCI NIH HHS/United States
R01 CA140002/CA/NCI NIH HHS/United States
The leptin-signaling pathway and other genes involved with energy homeostasis (EH), have been examined in relation to breast cancer risk as well as to obesity. We test the hypothesis that genetic variation in EH genes influences survival after diagnosis with breast cancer and that body mass index (BMI) will modify that risk.
We evaluated associations between 10 energy homeostasis genes and survival among 1186 non-Hispanic white (NHW) and 1155 Hispanic/Native American women diagnosed with breast cancer. Percent Native American (NA) ancestry was determined from 104 Ancestry Informative Markers. Adaptive rank truncation product (ARTP) was used to determine gene and pathway significance.
The overall EH pathway was marginally significant for all-cause mortality among women with low NA ancestry (PARTP = 0.057). Within the pathway, ghrelin (GHRL) and leptin receptor (LEPR) were significantly associated with all-cause mortality (PARTP = 0.035 and 0.007, respectively). The EH pathway was significantly associated with breast cancer-specific mortality among women with low NA ancestry (PARTP = 0.038). Three genes, cholecystokinin (CCK), GHRL, and LEPR were significantly associated with breast cancer-specific mortality among women with low NA ancestry (PARTP = 0.046, 0.015, and 0.046, respectively) while neuropeptide Y (NPY) was significantly associated with breast cancer-specific mortality among women with higher NA ancestry (PARTP = 0.038). BMI did not modify these associations.
Our data support our hypothesis that certain EH genes influence survival after diagnosis with breast cancer; associations appear to be most important among women with low NA ancestry.
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