New Aspects in the Epidemiology of Lung Cancer - The Women's Epidemic

New Aspects in the Epidemiology of Lung Cancer - The Women's Epidemic

Elisabeth Quoix
European Oncological Disease 2007
Published: October 2008
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Lung cancer is the most common cancer in the world and, by 2002, there were 1.35 million new cases, representing 12.4% of all new cancers.1 It is also the most frequent cause of death by cancer, with 1.18 million deaths.1 In women, the global incidence rate is 12.1 per 100,000 compared with 35.5 per 100,000 in men.

In the US, incidence and mortality standardised rates in 2000 were, respectively, 58.6 and 53.2 in males and 34.0 and 27.2 in females, with a sex ratio of 1.7.2 In females, mortality due to lung cancer has been greater than mortality due to breast cancer since 1987.3 In Europe, lung cancer is the most frequent cause of death by cancer in males. Sex ratios differ significantly between the European countries, reflecting differences in smoking habits. The lowest sex ratio is in Denmark (1.7), and the highest in Spain (13.4). While stabilisation or even a decrease in the number of lung cancers in males is emerging in most European countries, mortality due to lung cancer in females is increasing.4 In western Asia, the agestandardised incidence is 33.1 in males and 5.5 in females (sex ratio: 1.6).

Lung Cancer – Attributable to Active Tobacco Smoking in Women
Smoking habits vary within the different countries in Europe, with a significant decrease in tobacco consumption in the UK, Sweden and Finland between 1970 and 1994 and a significant increase in Portugal (+64.2%).5 Even if active tobacco smoking is the main cause of lung cancer in females, the attributable risk is inferior to that noted in males. Worldwide, in 2000 an estimated 85% of lung cancer cases in men and 47% in women were attributable to tobacco smoking.1 In the US, the proportion attributable to tobacco smoking in females is pretty much the same as in males. Moreover, there is now a convergence between lung cancer incidence in the youngest birth cohorts, reflecting the convergence in cigarette use in males and females.6 In Europe, about 70% of lung cancer cases in females are attributed to an active smoking habit versus 85% in males,7 whereas in Asia very few lung cancer cases in females are attributable to tobacco smoking. Even if the incidence of lung cancer in male non-smokers is consistently higher than in female non-smokers,8 the proportion of non-smokers in females with lung cancer is rather significant compared with males in all studies.9-11

Higher Tobacco-smoke Susceptibility in Females
Some case-control studies suggest a higher susceptibility to tobacco for females. A 1993 analysis found an odds ratio of 27.9 (95% confidence interval (CI) 14.9–52) for women who have smoked 40 pack-years (one pack a day for 40 years or two packs a day for 20 years, etc.) relative to lifelong non-smokers, versus 9.6 (95% CI 5.64–16.3) for males.12 Also, in an American Health Foundation case-control study, the relative risk of female smokers was estimated to be 1.5 times that of males.13 On the other hand, cohort studies demonstrated either no difference between genders regarding the risk linked to tobacco-smoke exposure or a higher risk in men.14–16 There are many differences between genders that could favour a higher susceptibility to tobacco in females. Capacity of DNA repair is inferior in females.17 DNA-adduct formation due to tobacco smoke is more frequent in females than in males, regardless of the level of smoking, and CYP1A1 (a gene involved in phase I of the metabolism of polycyclic aromatic hydrocarbons) level of expression is higher in females.18 P53 transversion mutation (G:C T:A) is of high frequency in human lung cancer and probably the result of DNA damage induced by carcinogens of tobacco smoke. In non-tumoral lung tissue, transversion and DNA adducts were more frequent in females even though tobacco exposure was less than in males.19

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