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Genetic variants in the mTOR pathway and interaction with body size and weight gain on breast cancer risk in African-American and European-American women
  • Published Date:
    Jun 17 2016
  • Source:
    Cancer Causes Control. 27(8):965-976.


Public Access Version Available on: August 01, 2017 information icon
Please check back on the date listed above.
Details:
  • Pubmed ID:
    27314662
  • Pubmed Central ID:
    PMC4958603
  • Description:
    Purpose

    Positive energy imbalance and growth factors linked to obesity promote the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (mTOR) pathway. As the obesity-breast cancer associations differ between European-American (EA) and African-American (AA) women, we investigated genetic variants in the mTOR pathway and breast cancer risk in these two racial groups.

    Methods

    We examined 400 single nucleotide polymorphisms (SNPs) in 31 mTOR pathway genes in the Women’s Circle of Health Study with 1263 incident breast cancers (645 EA, 618 AA) and 1382 controls (641 EA, 741 AA). Multivariable logistic regression was performed separately within racial groups. Effect modification was assessed for measured body size and weight gain since age 20.

    Results

    In EA women, variants in FRAP1 rs12125777 (intron), PRR5L rs3740958 (synonymous-coding), and CDKAL1 rs9368197 (intron) were associated with increased breast cancer risk, while variants in RPTOR rs9900506 (intron) were associated with decreased risk (nominal P-trend for functional and FRAP1 SNPs or P adjusted for correlated test [PACT] <0.05). For AA women, variants in RPTOR rs3817293 (intron), PIK3R1 rs7713645 (intron), and CDKAL1 rs9368197 were associated with decreased breast cancer risk. The significance for FRAP1 rs12125777 and RPTOR rs9900506 in EA women did not hold after correction for multiple comparisons. The risk associated with FRAP1 rs12125777 was higher among EAs who had body mass index ≥30 kg/m2 (odds ratio=7.69, 95% CI=2.11–28.0; P-interaction=0.007) and gained weight ≥35 lb. since age 20 (odds ratio=3.34, 95% CI=1.42–7.85; P-interaction=0.021), compared to their counterparts.

    Conclusions

    The mTOR pathway may be involved in breast cancer carcinogenesis differently for EA and AA women.

  • Document Type:
  • Collection(s):
  • Funding:
    U58 DP003931/DP/NCCDPHP CDC HHS/United States
    P30 CA016056/CA/NCI NIH HHS/United States
    P30 CA072720/CA/NCI NIH HHS/United States
    P01 CA151135/CA/NCI NIH HHS/United States
    K22 CA138563/CA/NCI NIH HHS/United States
    R01 CA100598/CA/NCI NIH HHS/United States
  • Supporting Files:
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