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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    • "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.
    Cancers 12/2012; 4(4):969-88. DOI:10.3390/cancers4040969
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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.
    Journal of Epidemiology 04/2012; 22(4):364-9. DOI:10.2188/jea.JE20110123 · 3.02 Impact Factor
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    ABSTRACT: In the post-intervention period of the Women's Health Initiative (WHI) trial, women assigned to treatment with oestrogen plus progestin had a higher risk of cancer than did those assigned to placebo. Results also suggested that the combined hormone therapy might increase mortality from lung cancer. To assess whether such an association exists, we undertook a post-hoc analysis of lung cancers diagnosed in the trial over the entire follow-up period. The WHI study was a randomised, double-blind, placebo-controlled trial undertaken in 40 centres in the USA. 16 608 postmenopausal women aged 50-79 years with an intact uterus were randomly assigned by a computerised, stratified, permuted block algorithm to receive a once-daily tablet of 0.625 mg conjugated equine oestrogen plus 2.5 mg medroxyprogesterone acetate (n=8506) or matching placebo (n=8102). We assessed incidence and mortality rates for all lung cancer, small-cell lung cancer, and non-small-cell lung cancer by use of data from treatment and post-intervention follow-up periods. Analysis was by intention to treat. This study is registered with, number NCT00000611. After a mean of 5.6 years (SD 1.3) of treatment and 2.4 years (0.4) of additional follow-up, 109 women in the combined hormone therapy group had been diagnosed with lung cancer compared with 85 in the placebo group (incidence per year 0.16%vs 0.13%; hazard ratio [HR] 1.23, 95% CI 0.92-1.63, p=0.16). 96 women assigned to combined therapy had non-small-cell lung cancer compared with 72 assigned to placebo (0.14%vs 0.11%; HR 1.28, 0.94-1.73, p=0.12). More women died from lung cancer in the combined hormone therapy group than in the placebo group (73 vs 40 deaths; 0.11%vs 0.06%; HR 1.71, 1.16-2.52, p=0.01), mainly as a result of a higher number of deaths from non-small-cell lung cancer in the combined therapy group (62 vs 31 deaths; 0.09%vs 0.05%; HR 1.87, 1.22-2.88, p=0.004). Incidence and mortality rates of small-cell lung cancer were similar between groups. Although treatment with oestrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, it increased the number of deaths from lung cancer, in particular deaths from non-small-cell lung cancer. These findings should be incorporated into risk-benefit discussions with women considering combined hormone therapy, especially those with a high risk of lung cancer. National Heart, Lung and Blood Institute, National Institutes of Health.
    The Lancet 09/2009; 374(9697):1243-51. DOI:10.1016/S0140-6736(09)61526-9 · 45.22 Impact Factor
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