Jianjun Zhang

MD, PhD

Indiana University

Professor

PLCO (Learn more about this study)

PLCO-87

May 30, 2014

Fat intake modifies the association between smoking and lung cancer risk

Although cigarette smoking is the primary cause of lung cancer, it alone cannot explain large differences in lung cancer incidence and mortality worldwide. During the last three decades, age-adjusted male lung cancer mortality rates have been remarkably higher in Hungary than in Japan, but per capita cigarette consumption has remained lower in Hungary than in Japan. It is still unknown why this lung cancer paradox occurs. Clearly, there is a gap in our understanding of lung cancer etiology. Our long-term goal is to develop innovative strategies for preventing lung cancer that are based on an improved understanding of its etiology. The objective of this application is to investigate the causes of the lung cancer paradox. Our central hypothesis is that different types of fat interact with cigarette smoking to modulate lung cancer risk. We have generated this hypothesis on the basis of our preliminary data and an extensive literature review. Epidemiologic studies show that the association between cigarette smoking and lung cancer is remarkably stronger in western countries than in eastern Asia. A major difference between the western and oriental diets is intake of total fat and saturated fat. Both are much higher in the west. Animal studies have revealed that lung tumors induced by tobacco carcinogens are promoted by saturated fat but inhibited by n-3 polyunsaturated fat. Collectively, these data suggest that the lung cancer paradox primarily occurs as a result of the interactions between types of fat and smoking of cigarettes. The rationale of this project is that, once our hypothesis is corroborated, modifying dietary fat intake could reduce lung cancer risk among smokers who do not intend to quit or cannot quit smoking, former smokers who have tobacco carcinogens accumulated in their lungs, and individuals who are exposed to secondhand smoke (passive smokers). We propose to test our hypothesis using existing data collected from subjects in the Prostate, Lung, Colorectal, and Ovary cancer prevention trial (PLCO). In the PLCO, data on smoking and other risk factors were gathered with a baseline questionnaire, and diet was assessed with Dietary Questionnaire (DQX) and Dietary History Questionnaire (DHQ) (introduced 5 years after the trial started). Cox regression will be performed to examine the interactions between types of fat and cigarette smoking in relation to lung cancer risk. At the completion of this project, it is our expectation that we will have elucidated that fat-smoking interactions primarily account for the lung cancer paradox. Such expected results are significant because they will shed new light on lung cancer etiology and thus open a novel avenue towards more effective prevention of this lethal disease. The proposed research is innovative because our projected results obtained from a large national cohort study would change our lung cancer prevention strategies from currently relying solely on smoking prevention and cessation to a comprehensive consideration of smoking control and modification of dietary fat intake.

Specific Aim 1: Evaluate the interactions between types of fat and cigarette smoking in relation to lung cancer risk. We hypothesize that lung cancer risk associated with cigarette smoking is greater among subjects with a higher intake of saturated fat and/or a lower intake of monounsaturated fat (MUFA) or polyunsaturated fat (PUFA).

Specific Aim 2: Investigate differences in fat-smoking interactions in relation to lung cancer risk by smoking products, tumor histology, and tumor stage. We hypothesize that the strength of the fat-smoking interactions varies by smoking products (e.g. filtered vs. unfiltered cigarettes), tumor histology (small cell carcinoma, squamous cell carcinoma, adenocarcinoma, and large cell carcinoma), and tumor stage (advanced vs. non-advanced).