Fat intake modifies association between cigarette smoking and lung cancer in a prospective cohort study: A potential explanation for the lung cancer paradox

Background & aims: It remains unclear why the association between cigarette smoking and lung cancer was substantially stronger in Western countries than in Asian countries. As experimental studies have revealed that fat intake modulates tobacco carcinogen metabolism and the growth of transplanted or carcinogen-induced lung tumors in mice, the present study sought to investigate whether the association between cigarette smoking and lung cancer was modified by intake of total fat and types of fat (saturated, monounsaturated, and polyunsaturated fats) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Methods: During a median follow-up of 8.9 years, 1,425 cases of lung cancer were documented from 100,864 participants eligible for the present analysis. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results: After adjustment for established or suspected confounders, the strength of the association between cigarette smoking and lung cancer was remarkably larger among individuals with high fat intake. HRs (95% CIs) comparing current with never smokers were 23.0 (13.4, 39.6), 32.7 (20.3, 52.8), and 59.8 (30.2, 118.2) for the tertile 1 (<= 13.48 g/day), tertile 2 (13.49-21.89 g/day), and tertile 3 (>= 21.90 g/day) of saturate fat intake, respectively. A similar pattern of the non-significant interaction was observed when the accumulated amount of cigarette smoking (1-19, 20-39, and >= 40 vs. 0 pack-years) was entered into the regression models. Conclusions: The present study showed that lung cancer risk associated with both the status and accumulated amount of cigarette smoking was remarkably stronger in individuals with high intakes of fat, particularly saturated fat. However, this interaction was not statistically significant and thus warrants further investigations in other studies. (c) 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.