Reproductive Factors, Hormone Use, and Risk for Lung Cancer in Postmenopausal Women, the Nurses' Health Study

Division of Hematology-Oncology, Tufts Medical Center, Boston, Massachusetts, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 10/2010; 19(10):2525-33. DOI: 10.1158/1055-9965.EPI-10-0450
Source: PubMed


There is increasing evidence suggesting that female hormones may play a significant role in lung cancer development. We evaluated the associations between reproductive factors, exogenous hormone use, and lung cancer incidence in the Nurses' Health Study.
We assessed age at menopause, age at menarche, type of menopause, parity, age at first birth, postmenopausal hormone (PMH) use, and past oral contraceptive use in 107,171 postmenopausal women. Cox models were used to estimate the hazard ratios for each exposure, adjusting for smoking and other covariates.
We identified 1,729 lung cancer cases during follow-up from 1984 to 2006. Menopause onset before 44 years of age (hazard ratio, 1.39; 95% confidence interval, 1.14-1.70) and past oral contraceptive use for >5 years (hazard ratio, 1.22; 95% confidence interval, 1.05-1.42) were associated with increased lung cancer risk. These associations were strongest in current smokers and small cell histology. In never smokers, increased parity was associated with decreased risk among parous women (P trend = 0.03), whereas in current smokers, older age at first birth was associated with increased risk (P trend = 0.02). PMH use was not associated with overall lung cancer incidence. However, nonsignificant results of increased risk in adenocarcinoma were seen with current PMH use.
Our findings suggest female hormones may influence lung carcinogenesis, although the effect is likely modest, varied by histologic subtype, and altered by smoking.
Further investigation of the pathophysiology of female hormones in lung cancer subtypes and their interaction with smoking will lead to better understanding of lung carcinogenesis.

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    • "However, the limited number of observed cases precluded firm conclusions. Most of the scientific literature on oral contraceptive use (OC) points to no association with lung cancer risk (Taioli and Wynder, 1994; Elliott and Hannaford, 2006; Kabat et al, 2007; Schwartz et al, 2007; Weiss et al, 2008; Seow et al, 2009; Hannaford et al, 2010; Vessey et al, 2010; Meinhold et al, 2011), with two possible exceptions showing, however, opposite results: a reduced lung cancer risk among ever OC users in a case–control study (Kreuzer et al, 2003) and a slightly increased risk among women using OC for 45 years in a cohort study (Baik et al, 2010). "
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    ABSTRACT: Background: The association between oral contraceptive (OC) use, hormone replacement therapy (HRT) and lung cancer risk in women is still debated. Methods: We performed a pooled analysis of six case–control studies (1961 cases and 2609 controls) contributing to the International Lung Cancer Consortium. Potential associations were investigated with multivariable unconditional logistic regression and meta-analytic models. Multinomial logistic regressions were performed to investigate lung cancer risk across histologic types. Results: A reduced lung cancer risk was found for OC (odds ratio (OR)=0.81; 95% confidence interval (CI): 0.68–0.97) and HRT ever users (OR=0.77; 95% CI: 0.66–0.90). Both oestrogen only and oestrogen+progestin HRT were associated with decreased risk (OR=0.76; 95% CI: 0.61–0.94, and OR=0.66; 95% CI: 0.49–0.88, respectively). No dose-response relationship was observed with years of OC/HRT use. The greatest risk reduction was seen for squamous cell carcinoma (OR=0.53; 95% CI: 0.37–0.76) in OC users and in both adenocarcinoma (OR=0.79; 95% CI: 0.66–0.95) and small cell carcinoma (OR=0.37; 95% CI: 0.19–0.71) in HRT users. No interaction with smoking status or BMI was observed. Conclusion: Our findings suggest that exogenous hormones can play a protective role in lung cancer aetiology. However, given inconsistencies with epidemiological evidence from cohort studies, further and larger investigations are needed for a more comprehensive view of lung cancer development in women.
    Full-text · Article · Sep 2013 · British Journal of Cancer
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    • "Interestingly, a parallel trial of estrogen alone HRT versus placebo did not affect the lung cancer outcome [84], thus increasing interest in better understanding of the progesterone pathway in lung cancer. There have been a number of observational studies investigating the role of HRT in lung cancer and the results have been mixed with reports of both increased and decreased risk as well as of null associations [85,86,87]. The results of these studies are difficult to interpret given the heterogeneity in methodology such as exposure measurement and adjusted covariates. "
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    ABSTRACT: Lung cancer is the leading cause of cancer death in U.S. and represents a major public health burden. Epidemiologic data have suggested that lung cancer in women may possess different biological characteristics compared to men, as evidenced by a higher proportion of never-smokers among women with lung cancer. Emerging data indicate that female hormones such as estrogen and progesterone play a significant role in lung carcinogenesis. It has been reported that estrogen and progesterone receptors are expressed in lung cancer cell lines as well as in patient-derived tumors. Hormone related risk factors such as hormone replacement therapy have been implicated in lung carcinogenesis and several preclinical studies show activity of anti-estrogen therapy in lung cancer. In this review, we summarize the emerging evidence for the role of reproductive hormones in lung cancer and implications for lung cancer therapy.
    Full-text · Article · Dec 2012 · Cancers
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    • "Only a few studies examined the role of parity in the development of lung cancer, and the results have been mixed. Some studies found inverse associations between parity and lung cancer risk,16–22 while other epidemiologic studies reported null23–25 or positive associations.26 "
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    ABSTRACT: We examined the association between parity and risk of lung cancer. The study cohort consisted of all women with a record of a first singleton birth in the Taiwanese Birth Register between 1978 and 1987. We tracked each woman from the time of their first childbirth to 31 December 2009. Follow-up was terminated when the mother died, when she reached age 50 years, or on 31 December 2009, whichever occurred first. The vital status of mothers was ascertained by linking records with the computerized mortality database. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) for death from lung cancer associated with parity. There were 1375 lung cancer deaths during 32 243 637.08 person-years of follow-up. The mortality rate of lung cancer was 4.26 cases per 100,000 person-years. As compared with women who had given birth to only 1 child, the adjusted HR was 1.13 (95% CI, 0.94-1.35) for women who had 2 children, 1.10 (0.91-1.33) for those who had 3 children, and 1.22 (0.96-1.54) for those who had 4 or more children. The findings suggest that premenopausal women of higher parity tended to have an increased risk of lung cancer, although the trend was not statistically significant.
    Full-text · Article · Apr 2012 · Journal of Epidemiology
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