Welcome to CDC Stacks | Hormone metabolism pathway genes and mammographic density change after quitting estrogen and progestin combined hormone therapy in the California Teachers Study - 32150 | CDC Public Access
Stacks Logo
Advanced Search
Select up to three search categories and corresponding keywords using the fields to the right. Refer to the Help section for more detailed instructions.
 
 
Help
Clear All Simple Search
Advanced Search
Hormone metabolism pathway genes and mammographic density change after quitting estrogen and progestin combined hormone therapy in the California Teachers Study
Filetype[PDF - 474.57 KB]


Details:
  • Pubmed ID:
    25499601
  • Pubmed Central ID:
    PMC4318222
  • Funding:
    HHSN261201000034C/PHS HHS/United States
    HHSN261201000035C/PHS HHS/United States
    HHSN261201000140C/PHS HHS/United States
    K05 CA136967/CA/NCI NIH HHS/United States
    P01 CA017054/CA/NCI NIH HHS/United States
    R01 CA77398/CA/NCI NIH HHS/United States
    U58DP003862-01/DP/NCCDPHP CDC HHS/United States
  • Document Type:
  • Collection(s):
  • Description:
    Introduction

    Mammographic density (MD) is a strong biomarker of breast cancer risk. MD increases after women start estrogen plus progestin therapy (EPT) and decreases after women quit EPT. A large interindividual variation in EPT-associated MD change has been observed, but few studies have investigated genetic predictors of the EPT-associated MD change. Here, we evaluate the association between polymorphisms in hormone metabolism pathway genes and MD changes when women quit EPT.

    Methods

    We collected mammograms before and after women quit EPT and genotyped 405 tagging single nucleotide polymorphisms (SNPs) in 30 hormone metabolism pathway genes in 284 non-Hispanic white participants of the California Teachers Study (CTS). Participants were ages 49 to 71 years at time of mammography taken after quitting EPT. We assessed percent MD using a computer-assisted method. MD change was calculated by subtracting MD of an ‘off-EPT’ mammogram from MD of an ‘on-EPT’ (that is baseline) mammogram. Linear regression analysis was used to investigate the SNP-MD change association, adjusting for the baseline ‘on-EPT’ MD, age and BMI at time of baseline mammogram, and time interval and BMI change between the two mammograms. An overall pathway and gene-level summary was obtained using the adaptive rank truncated product (ARTP) test. We calculated ‘P values adjusted for correlated tests (PACT)’ to account for multiple testing within a gene.

    Results

    The strongest associations were observed for rs7489119 in SLCO1B1, and rs5933863 in ARSC. SLCO1B1 and ARSC are involved in excretion and activation of estrogen metabolites of EPT, respectively. MD change after quitting was 4.2% smaller per minor allele of rs7489119 (P = 0.0008; PACT = 0.018) and 1.9% larger per minor allele of rs5933863 (P = 0.013; PACT = 0.025). These individual SNP associations did not reach statistical significance when we further used Bonferroni correction to consider the number of tested genes. The pathway level summary ARTP P value was not statistically significant.

    Conclusions

    Data from this longitudinal study of EPT quitters suggest that genetic variation in two hormone metabolism pathway genes, SLCO1B1 and ARSC, may be associated with change in MD after women stop using EPT. Larger longitudinal studies are needed to confirm our findings.

    Electronic supplementary material

    The online version of this article (doi:10.1186/s13058-014-0477-8) contains supplementary material, which is available to authorized users.