CIGARETTE SMOKING AND GENDER-DIFFERENCES IN LUNG CANCER RISK: A MOLECULAR EPIDEMIOLOGY

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The most established etiologic risk factor for lung cancer is cigarette smoking. Differing distributions of histologic types of lung cancer between males and females may be associated with differences in smoking patterns, but this does not fully explain the observed gender differences. There is growing epidemiological evidence that, when smoking habits are comparable, women incur a higher risk (2-3 times) for small cell lung carcinoma than men. Molecular epidemiological studies have also indicated gender differences in the genetic and biochemical alterations in lung cancer.We investigated polymorphisms of CYP1A1 (Msp I and IIe-Val) and GSTs (M1 and T1) in 152 lung cancer patients (male:female = 110:42). We also measured phenotypic activity of GYP1A1 (aryl hydrocarbon hydroxylase, AHH) in peripheral mitogen-treated lymphocytes. No gender-differences were observed between age-, cigarette dose- and season of the year-adjusted AHH activity/AHH inducibility (3-methylcholanthren-induced AHH activity/non-induced AHH activity). Proportion of CYP1A1 Msp I, CY1PA1 De-Val, GSTM1 and GSTT1 genotypes in males and females was not significantly different. Gender difference in aromatic DNA-adducts was not evident.Whether lung cancer represents a different disease in women than in men is unclear. If the hypothesis regarding gender differences in genetic susceptibility to lung cancer proves to be true, education for reducing passive and active exposure to cigarette smoke must have a high priority for female's health.