Reproductive and Hormonal Factors and Lung Cancer Risk in the NIH-AARP Diet and Health Study Cohort

Abstract

Background Lung cancer exhibits unique patterns among women, including high adenocarcinoma rates among non-smokers. Inconsistent findings regarding hormonal factors on risk may reflect incomplete control for confounding, misclassification of exposures, or insufficient attention to variation by histology. Methods Among 185,017 women, ages 50–71 years, recruited during 1995–1996 for the NIH-AARP Diet and Health Study, we identified 3,512 incident lung cancers (including 276 in never smokers) in follow-up through December 2006. Multivariable Cox proportional hazards models estimated relative risks (RRs) and 95% confidence intervals (CIs) for self-reported hormonally-related risk factors. Results After adjustment for smoking and other confounders, subjects with late menarche were at reduced risk, with the association specific for adenocarcinomas (RR=0.72 for menarche 15+ vs. <11, p for trend<0.01). Subjects with early ages at ovarian cessation (either from natural menopause or bilateral oophorectomy) were at an increased risk for adenocarcinomas and squamous cell tumors, but the associations were strongest for smokers, suggesting either residual confounding or an enhanced effect of menopausally-related factors among subjects with decreased endogenous estrogens. In contrast, we saw no relationships of risk with either parity, age at first birth, or exogenous hormone use. Conclusions Elevated levels of hormones may adversely affect lung function early in life, while assisting with cellular and immunologic responses later in life. Additional attention towards the role of hormonal factors may further our understanding of lung carcinogenesis. Impact Our findings provide some support for a role of hormonal factors in the etiology of lung cancer, although the mechanisms appear complicated.

Long-Term Mortality Associated With Oophorectomy Compared With Ovarian Conservation in the Nurses' Health Study

“…Although our earlier findings on oophorectomy and increased risk of incident lung cancer were unexpected, other studies subsequently found a similar association. (7,15,16) These observations that oophorectomy may affect lung cancer risk merit further investigation.…”

Bilateral oophorectomy and risk of cancer in African American women

“…A protective effect of endogenous estrogens on colorectal and lung cancer risk is supported by studies showing that earlier age at natural menopause is associated with increased risk of colorectal cancer (31) and lung cancer (17, 18, 32, 33). If exogenous estrogens are protective, as suggested by studies that have observed inverse associations between menopausal hormone use and risk of colorectal cancer (19, 20) and lung cancer (21, 22), this might explain why an association of bilateral oophorectomy with colorectal and lung cancer risk was more apparent in women who had little or no menopausal hormone use.…”

Specifying the ovarian cancer risk threshold of ‘premenopausal risk-reducing salpingo-oophorectomy’ for ovarian cancer prevention: a cost-effectiveness analysis

“…However, these additional deaths from cancer that were observed could have been confounded by smoking or other risk-related behaviours. Much larger cohort studies have shown smoking per se is linked to menopause,57 58 and after stratification by smoking, any increase in lung cancer risk reported following oophorectomy is limited to those who smoke 57. Furthermore, the EPIC study (337 802 women) reported lack of any significant association of colorectal cancer risk with age or surgical menopause 59.…”