Higher Lung Cancer Incidence in Young Women

The basis for incidence differences is not fully explained by sex differences in smoking behaviours

Findings of the study published on 24 May 2018 in the New England Journal of Medicine show that the patterns of historically higher incidence rates of lung cancer in US among men than among women have reversed among non-Hispanic whites and Hispanics born since the mid-1960s, and they are not fully explained by sex differences in smoking behaviours. Future studies are needed to identify reasons for the higher incidence of lung cancer among young women.

The authors wrote in study background that previous studies showed a higher incidence of lung cancer among young women than among young men in the US. A group of researchers from the Surveillance and Health Services Research, American Cancer Society in Atlanta and the Division of Cancer Epidemiology and Genetics, National Cancer Institute in Rockville, MD examined up-to-date data on the incidence of lung cancer and the prevalence of cigarette smoking in the US according to sex and race or ethnic group to concurrently assess whether the incidence of lung cancer in contemporary cohorts is higher among women than among men and, if so, whether this pattern can be fully explained by sex differences in smoking behaviours.

In particular, they examined the nationwide population-based incidence of lung cancer according to sex, race or ethnic group, age group (30 to 34, 35 to 39, 40 to 44, 45 to 49, and 50 to 54 years), year of birth (1945 to 1980), and calendar period of diagnosis (1995–1999, 2000–2004, 2005–2009, and 2010–2014). They calculated female-to-male incidence rate ratios. They also examined the prevalence of cigarette smoking, using data from the US National Health Interview Survey from 1970 to 2016.

Over the past two decades, the age-specific incidence of lung cancer has generally decreased among both men and women 30 to 54 years of age in all races and ethnic groups, but the declines among men have been steeper. Consequently, among non-Hispanic whites, the female-to-male incidence rate ratios increased, exceeding 1.0 in the age groups of 30 to 34, 35 to 39, 40 to 44, and 45 to 49 years. For example, the female-to-male incidence rate ratio among whites 40 to 44 years of age increased from 0.88 (95% confidence interval [CI], 0.84 to 0.92) during the 1995–1999 period to 1.17 (95% CI, 1.11 to 1.23) during the 2010–2014 period.

The crossover in sex-specific rates occurred among non-Hispanic whites born since 1965. Sex-specific incidence rates converged among non-Hispanic blacks, Hispanics, and non-Hispanic Asians and Pacific Islanders but crossed over from a higher incidence among men to a higher incidence among women only among Hispanics.

The prevalence of cigarette smoking among women born since 1965 has approached, but generally not exceeded, the prevalence among men.

The authors explained that the risk of adenocarcinoma, a lung cancer subtype that is more common among women than among men, decreases more slowly than the risk of other types of lung cancer after smoking cessation. There has been some limited biologic and genetic evidence to support a higher susceptibility among women, including a higher frequency of mutations in critical driver genes, such as TP53 and the KRAS oncogene.

Factors other than active tobacco use account for about 15% of cases of lung cancer in women and 10% in men. Occupational exposure to lung carcinogens, such as asbestos and arsenic, which have synergistic effects with smoking and were historically more common among men than among women, have decreased dramatically over the past several decades. This may have contributed to the steeper decline in lung cancer among men. Although exposure to second hand smoke has also decreased substantially over the past several decades, the decline has not been shown to differ significantly between men and women. Similarly, changes in exposure to outdoor air pollution are not expected to differ according to sex. In contrast, results of pooled, large cohort studies have shown that the incidence of lung cancer among non-smokers appears to be slightly higher among women than among men younger than 70 years of age. It will be difficult, however, to estimate how much of the excess risk of lung cancer among women is due to sex differences in temporal changes in exposure to non-tobacco causes and in background rates.

More frequent detection of indolent lung tumours in women than in men through screening or diagnostic imaging is an alternative explanation for the higher rates of lung cancer among women.

Besides several caveats that unlikely may affect the interpretation of main findings, a strength of the current study is the use of nationwide, high-quality population-based data on both lung cancer incidence and smoking prevalence. Therefore, the authors concluded that the historical patterns of higher incidence rates of lung cancer among men than among women have reversed among non-Hispanic whites and Hispanics born since the mid-1960s and are not fully explained by sex differences in smoking behaviours.

The findings have important implications for public health. They may foreshadow a higher future burden of overall lung cancer among women than among men as younger cohorts age, which further underscores the need to intensify anti-tobacco measures to decrease smoking among young women. The findings also call for continued monitoring of sex-specific risks of lung cancer and for aetiology studies, including studies of sex differences in smoking-related susceptibility to lung cancer, to identify reasons for the higher rates of lung cancer among young women.

The study was supported by the American Cancer Society.

Drs. Devesa and Thun contributed equally to this article. 

Reference

Jemal A, Miller KD, Ma J, et al. Higher Lung Cancer Incidence in Young Women Than Young Men in the United States. NEJM2018; 378(21):1999-2009. doi: 10.1056/NEJMoa1715907