Higher lung cancer risk among female never-smokers than males in a large married couple study

Whether female being more susceptible to lung cancer among never smokers (LCNS) than males has been a long-standing debate.

A total of 26,339 married heterosexual couples included in this cohort study. Truncated (40-89) age-standardized incidence rates and incidence rate ratio (IRR) of lung cancer were calculated and compared between the two sexes. Cox regression models were used to estimate hazard ratio (HR) for evaluating sex differences in lung cancer risk.

In this large couples cohort study the prevalence of ever smoking was 2.1 % in wives and 65.4 % in husbands. Over a median follow-up of 12.5 years, incident lung cancer was documented in 293 wives and 500 husbands. The truncated age-standardized incidence rate per 100,000 person-years in all couples was significantly lower in wives (56.1) than their husbands (117.4), with an IRR of 0.48 for wives vs husbands. A similar pattern was observed among dual-smoker couples. However, the sex difference diminished when further adjusting for the duration and intensity of cigarette smoking. In contrast, among dual-nonsmoker couples, the corresponding age-standardized rate was significantly higher in wives (52.6) than their husbands (33.4), with an IRR of 1.57. Multivariable adjustment did not alter the result, with an HR for wives vs husbands of 1.54 (95 % CI, 1.05-2.27).

This study, for the first time, using a large cohort of married couples, demonstrates that females are more susceptible to LCNS than males.