Person:

Shafrir, Amy

Background: This study estimates the potential population health burden from exposure to combustion-derived particulate air pollution in domestic settings in Ireland and Scotland. Methods: The study focused on solid fuel combustion used for heating and the use of gas for cooking. PM2.5 (particulate matter with an aerodynamic diameter < 2.5 μm) was used as the pollutant mixture indicator. Measured PM2.5 concentrations in homes using solid fuels were adjusted for other sources of PM2.5 by subtracting PM2.5 concentrations in homes using gas for cooking but not solid fuel heating. Health burden was estimated for exposure indoors 6 pm - midnight, or all day (24-hour), by combining estimated attributable annual PM2.5 exposures with (i) selected epidemiological functions linking PM2.5 with mortality and morbidity (involving some re-scaling from PM10 to PM2.5, and adjustments ‘translating’ from concentrations to exposures) and (ii) on the current population exposed and background rates of morbidity and mortality. Results: PM2.5 concentrations in coal and wood burning homes were similar to homes using gas for cooking, used here as a baseline (mean 24-hr PM2.5 concentrations 8.6 μg/m3) and so health impacts were not calculated. Concentrations of PM2.5 in homes using peat were higher (24-hr mean 15.6 μg/m3); however, health impacts were calculated for the exposed population in Ireland only; the proportion exposed in Scotland was very small. The assessment for winter evening exposure (estimated annual average increase of 2.11 μg/m3 over baseline) estimated 21 additional annual cases of all-cause mortality, 55 of chronic bronchitis, and 30,100 and 38,000 annual lower respiratory symptom days (including cough) and restricted activity days respectively. Conclusion: New methods for estimating the potential health burden of combustion-generated pollution from solid fuels in Irish and Scottish homes are provided. The methodology involves several approximations and uncertainties but is consistent with a wider movement towards quantifying risks in PM2.5 irrespective of source. Results show an effect of indoor smoke from using peat (but not wood or coal) for heating and cooking; but they do not suggest that this is a major public health issue.

Ovarian cancer etiology is not fully elucidated and few modifiable risk factors have been identified. Ovarian cancer treatment has changed over time; however, survival is still poor. I investigated reproductive and hormonal factors in relation to ovarian cancer risk and survival. In the Nurses’ Health Study (NHS), NHSII and New England Case-Control Study (NECC), I evaluated reproductive and hormonal factors and incidence of ovarian cancer characterized by estrogen receptor-α (ERα) and progesterone receptor (PR) status using polytomous logistic regression. In the NHSII, I investigated oral contraceptive (OC) use and ovarian cancer risk using Cox proportional hazards models. In the NECC, I evaluated the association of pre-diagnostic reproductive and hormonal factors with overall survival and platinum resistance among ovarian cancer cases using Cox proportional hazards models. Postmenopausal status was associated with an increased risk of PR- tumors (OR: 2.07; 95%CI: 1.15-3.75; p-heterogeneity=0.01) and age at natural menopause was inversely associated with PR- tumors (OR, per 5yr: 0.77; 95%CI: 0.61-0.96; p-het=0.01). Increasing duration of postmenopause was differentially associated by PR status (p-het=0.0009). In OC analyses, OC use of <6 months was associated with an increased risk of ovarian cancer (HR: 1.53; 95%CI: 1.00-2.35) and a suggestion of a decreased risk with >10 years of OC use (HR: 0.84; 95%CI: 0.51-1.39) compared to never use. The increased risk appeared to be driven by duration of mestranol use. In survival analyses, self-reported endometriosis was associated with a 29% (95%CI: 0.54-0.94) decreased risk of total death. Additionally, longer duration of hormone therapy (HT) was associated with a decreased risk of death (HR, ≥5yr vs. never: 0.70; 95%CI: 0.54-0.89). Further >5 years of HT use was associated with a decreased risk of platinum resistance. While our results need to be confirmed in other studies, they suggest that the development of ovarian tumors through hormonal pathways differs by menopausal status, the association between OC use and ovarian cancer differs between younger and older birth cohorts, and that various reproductive and hormonal factors are associated with ovarian cancer survival. These results may help in further understanding ovarian cancer etiology and providing recommendations for ovarian cancer prevention and survival.

Background: Ovarian cancer survival is poor, particularly for platinum-resistant cases. The previous literature on pre-diagnostic reproductive factors and ovarian cancer survival has been mixed. Therefore, we evaluated pre-diagnostic reproductive and hormonal factors with overall survival and, additionally, platinum-chemotherapy resistance. Methods: We followed 1649 invasive epithelial ovarian cancer cases who were enrolled between 1992 and 2008 for overall mortality within the New England Case-Control Study and abstracted chemotherapy data on a subset (n=449). We assessed pre-diagnostic reproductive and hormonal factors during in-person interviews. We calculated hazard ratios (HRs) using Cox-proportional hazards models. Results: We observed 911 all-cause deaths among 1649 ovarian cancer cases. Self-reported endometriosis and longer duration of hormone therapy use were associated with improved survival (HR: 0.72; 95% confidence interval (CI): 0.54–0.94 and HR, ⩾5 years vs never: 0.70; 95% CI: 0.55–0.90, respectively). Older age at menopause and menarche were associated with worse survival (HR, ⩽50 vs >50 years: 1.23; 95% CI: 1.03–1.46 and HR, 13 vs <13 years: 1.24; 95% CI: 1.06–1.44, respectively). We observed no association between oral contraceptive use, parity and tubal ligation, and overall survival. No significant associations were observed for any of the reproductive and hormonal factors and platinum resistance. Conclusions: These results suggest that pre-diagnostic exposures such as endometriosis and HT use may influence overall survival among ovarian cancer patients.