Reproductive factors and hormonal use and DNA repair polymorphisms XRCC1 and MGMT and adult-onset gliomas Public Deposited

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  • March 21, 2019
  • Felini, Martha J. Hunskor
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Gliomas are the most common and potentially most fatal of brain tumors. With few leads emerging, focus has reshifted to the consistent predisposition of glial tumors toward males. Previous studies using reproductive factors to evaluate whether hormones may play a role in gliomagenesis have been largely inconclusive. Using the population-based San Francisco Adult Glioma Study, we evaluated whether reproductive factors and exogenous hormone use were independently associated with gliomas and went further to evaluate cumulative exposure. Overall, reproductive and menstrual factors were not associated with gliomas. However, inverse associations were observed for ever exogenous hormone use (oral contraceptive use (OC): adjusted odd ratio (AOR) = 0.73, 95% CI, 0.49-1.10; postmenopausal hormone use (PHT): AOR = 0.53, 95% CI: 0.33-0.86). Risk estimates decreased with increasing duration of OC use among ever users. OC users who subsequently used PHT were at significantly reduced risk of gliomas (AOR = 0.45, 95% CI: 0.21-0.99), but departures from the multiplicative and additive scales were not statistically significant. Cumulative exposure was defined multiple ways and showed no clear pattern of association. Analysis by smoking status and histologic subtype was unrevealing. As a second line of investigation, we used the same parent study to evaluate whether DNA repair polymorphisms XRCC1 Arg399Gln, MGMT Leu84Phe, and MGMT Ile143Val were associated with gliomas among male and female participants. Significant associations were not found between XRCC1 and MGMT polymorphisms and gliomas. The adjusted odds ratio of the XRCC1 399Gln variant among whites was 0.96 (95% CI, 0.72-1.28). A weak positive association (AOR = 1.26; CI, 0.90-1.75) was observed for the MGMT Leu84Phe polymorphism (Leu or Phe/Phe versus Leu/Leu), an association that was stronger among males (AOR = 1.75; CI,1.12-2.74) and non-glioblastoma cases (AOR = 1.54; CI, 1.02-2.34). DNA repair polymorphisms did not notably modify risk estimates for the smoking-glioma association, suggesting little evidence of a multiplicative or additive joint effect between genotypes and cigarette smoking. Two way genegene interactions of XRCC1 and previously associated ERCC1 and ERCC2 repair genes were unremarkable.
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  • Olshan, Andrew
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  • University of North Carolina at Chapel Hill
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