The incidence of female lung cancer in developed countries has been increasing since 1950 and particularly in France where the cigarettes consumption has also increased. Since 1980, a growing number of epidemiological surveys have pinpointed the risk of female lung cancer related to smoking. Consecutively, a debate on gender differences in lung cancer risk has appeared, but still in progress nowadays. The reproductive factors could explain these differences. In order to have recent and reliable data on the association between cigarettes smoking and the risk of lung cancer in women and to compare the lung cancer risk associated with smoking exposure between genders, we analyzed the data of a French population-based case-control study, ICARE. The role of the reproductive factors in lung cancer was analyzed pooling, 9 international epidemiological studies included in ILCCO consortium.The ICARE study included 2276 male and 650 female cases and 2780 male and 775 female controls. Lifetime smoking exposure was represented by the comprehensive smoking index (CSI) which combines total duration of smoking, the mean intensity and the time since cessation. The pooled analysis of the reproductive factors included a total of 4547 cases and 4176 controls were included.Among the ever smokers, the relative risk of lung cancer was similar among men and women after adjustments for age, département, education, BMI, occupational exposure and chronic bronchitis. However, we found that women have a 2-fold greater risk than men of developing either small cell carcinomas or squamous cell carcinomas. Alternatively, the association was similar between men and women for the adenocarcinomas. As regard the reproductive factors, we found that longer is the age at menopause, lower is the lung cancer risk. Moreover, longer is the duration of cycle, lower is the lung cancer risk. The ovariectomy is also associated with an increasing risk of lung cancer.Our findings suggest that women might be more susceptible than men to develop small cell carcinoma or squamous cell carcinoma in response to the carcinogenic effect of cigarettes smoking. The analysis on the reproductive factors showed an inverse association between hormonal exposure and lung cancer indicating a likely complex relationship between the two factors.
