Reproductive and hormonal factors and the risk of lung cancer: the EAGLE study.

Evidence about the role for reproductive and hormonal factors in the etiology of lung cancer in women is conflicting. To clarify this question, we examined 407 female cases and 499 female controls from the Environment And Genetics in Lung cancer Etiology population-based case-control study. Subjects were interviewed in person using a computer-assisted personal interview to assess demographics, education, smoking history, medical history, occupational history, reproductive and hormonal factors. Associations of interest were investigated using logistic regression models, adjusted for catchment area and age (matching variables), cigarette smoking (status, pack-years and time since quitting). Additional confounding variables were investigated but did not substantially affect the results. We observed a reduced risk of lung cancer among women with later age at first live birth [≥31 years: odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.31-1.06, p-trend = 0.05], later age at menopause (≥51 years: OR = 0.49, 95%CI = 0.31-0.79, p-trend = 0.003) and longer reproductive periods (≥41 years: OR = 0.44, 95%CI = 0.25-0.79, p-trend = 0.01). A reduced risk was also observed for hormone replacement therapy (OR = 0.63, 95%CI = 0.42-0.95, p = 0.03) and oral contraceptive use (OR = 0.67, 95%CI = 0.45-1.00, p = 0.05) but no trend with duration of use was detected. Menopausal status (both natural and induced) was associated with an augmented risk. No additional associations were identified for other reproductive variables. This study suggests that women who continue to produce estrogens have a lower lung cancer risk. Large studies with great number of never smoking women, biomarkers of estrogen and molecular classification of lung cancer are needed for a more comprehensive view of the association between reproductive factors and lung cancer risk.