Diet and lifestyle factors interact with MAPK genes to influence survival: The Breast Cancer Health Disparities Study
Published Date:Jul 04 2014
Source:Cancer Causes Control. 25(9):1211-1225.
Pubmed Central ID:PMC4156917
Funding:1U58 DP000807-01/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
HHSN261201000036C/PHS HHS/United States
N01-PC-67000/PC/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
R03 CA121875/CA/NCI NIH HHS/United States
MAPK genes are activated by a variety of factors related to growth factors, hormones, and environmental stress.
We evaluated associations between 13 MAPK genes and survival among 1187 non-Hispanic white (NHW) and 1155 Hispanic/Native American women diagnosed with breast cancer. We assessed the influence of diet, lifestyle, and genetic ancestry on these associations. 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.
Associations were predominantly observed among women with lower NA ancestry. Specifically, the MAPK pathway was associated with all-cause mortality (PARTP=0.02), but not with breast cancer-specific mortality (PARTP=0.10). However, MAP2K1 and MAP3K9 were associated with both breast cancer-specific and all-cause mortality. MAPK12 (PARTP=0.05) was only associated with breast cancer-specific mortality, and MAP3K1 (PARTP=0.02) and MAPK1 (PARTP=0.05) were only associated with all-cause mortality. Among women with higher NA ancestry, MAP3K2 was significantly associated with all-cause mortality (PARTP=0.04). Several diet and lifestyle factors, including alcohol consumption, caloric intake, dietary folate, and cigarette smoking, significantly modified the associations with MAPK genes and all-cause mortality.
Our study supports an association between MAPK genes and survival after diagnosis with breast cancer, especially among women with low NA ancestry. The interaction between genetic variation in the MAPK pathway with diet and lifestyle factors for all women supports the important role of these factors for breast cancer survivorship.
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