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Genetic Variation in the JAK/STAT/SOCS signaling pathway influences breast cancer-specific mortality through interaction with cigarette smoking and use of aspirin/NSAIDs: The Breast Cancer Health Disparities Study
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Details:
  • Pubmed ID:
    25104439
  • Pubmed Central ID:
    PMC4167366
  • 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
    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
  • Document Type:
  • Collection(s):
  • Description:
    Purpose

    The Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-signaling pathway is involved in immune function and cell growth; genetic variation in this pathway could influence breast cancer risk.

    Methods

    We examined 12 genes in the JAK/STAT/SOCS-signaling pathway with breast cancer risk and mortality in an admixed population of Hispanic (2111 cases, 2597 controls) and non-Hispanic white (1481 cases, 1585 controls) women. Associations were assessed by Indigenous American (IA) ancestry.

    Results

    After adjustment for multiple comparisons, JAK1 (3 of 10 SNPs) and JAK2 (4 of 11 SNPs) interacted with body mass index (BMI) among pre-menopausal women, while STAT3 (4 of 5 SNPs) interacted significantly with BMI among post-menopausal women to alter breast cancer risk. STAT6 rs3024979 and TYK2 rs280519 altered breast cancer-specific mortality among all women. Associations with breast cancer-specific mortality differed by IA ancestry; SOCS1 rs193779, STAT3 rs1026916, and STAT4 rs11685878 associations were limited to women with low IA ancestry and associations with JAK1 rs2780890, rs2254002, and rs310245 and STAT1 rs11887698 were observed among women with high IA ancestry. JAK2 (5 of 11 SNPs), SOCS2 (1of 3 SNPs), and STAT4 (2 of 20 SNPs) interacted with cigarette smoking status to alter breast-cancer specific mortality. SOCS2 (1 of 3 SNPs) and all STAT3, STAT5A, and STAT5B SNPs significantly interacted with use of aspirin/NSAIDs to alter breast cancer-specific mortality.

    Conclusions

    Genetic variation in the JAK/STAT/SOCS pathway was associated with breast cancer-specific mortality. The proportion of SNPs within a gene that significantly interacted with lifestyle factors lends support for the observed associations.