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

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

Reproductive factors and hormone use and risk of adult gliomas

Previous research suggests there may be a hormonal influence on glioma risk as evidenced by lower rates in females, change in incidence rates around ages at menarche and menopause and presence of hormone receptors in glial tumors. Using the large San Francisco Bay Area Adult Glioma Study, we investigated whether reported reproductive factors and hormone use were associated with gliomas overall or with histologic subtypes among female cases (n=619) and controls (n=650). We found that reproductive factors were generally not associated with gliomas. Weak to moderately elevated odds ratios were observed for self-reported later age at menarche (14+ years old versus 12–13 years old: adjusted odds ratio (AOR) = 1.39, 95% confidence interval (CI): 1.02 –1.89), particularly for non-glioblastoma histologies (AOR = 1.64, 95% CI: 1.11–2.43). Inverse associations were observed for ever self-reported use of exogenous hormones (oral contraceptive use: AOR = 0.72, 95% CI: 0.53–0.99; postmenopausal hormone use: AOR = 0.56, CI: 0.37–0.84). However, cumulative hormone exposure defined multiple ways demonstrated no clear pattern of association. The results of this study suggest that any protective effect of hormones on gliomas may be limited to exogenous hormones, but a more detailed history of exogenous hormone use are needed to confirm findings

Reproductive factors and hormone use and risk of adult gliomas

Previous research suggests there may be a hormonal influence on glioma risk as evidenced by lower rates in females, change in incidence rates around ages at menarche and menopause and presence of hormone receptors in glial tumors. Using the large San Francisco Bay Area Adult Glioma Study, we investigated whether reported reproductive factors and hormone use were associated with gliomas overall or with histologic subtypes among female cases (n=619) and controls (n=650). We found that reproductive factors were generally not associated with gliomas. Weak to moderately elevated odds ratios were observed for self-reported later age at menarche (14+ years old versus 12–13 years old: adjusted odds ratio (AOR) = 1.39, 95% confidence interval (CI): 1.02 –1.89), particularly for non-glioblastoma histologies (AOR = 1.64, 95% CI: 1.11–2.43). Inverse associations were observed for ever self-reported use of exogenous hormones (oral contraceptive use: AOR = 0.72, 95% CI: 0.53–0.99; postmenopausal hormone use: AOR = 0.56, CI: 0.37–0.84). However, cumulative hormone exposure defined multiple ways demonstrated no clear pattern of association. The results of this study suggest that any protective effect of hormones on gliomas may be limited to exogenous hormones, but a more detailed history of exogenous hormone use are needed to confirm findings