Smoking and γ-Glutamyltransferase: Opposite Interactions with Alcohol Consumption and Body Mass Index

Background: Smoking has recently been suggested to synergistically interact with alcohol intake as a determinant of serum gamma-glutamyltransferase (γ-GT), an emergent powerful predictor of disease and mortality. This study investigated whether this also applies to higher smoking and alcohol exposure ranges and to body mass index (BMI), which likewise is strongly associated with γ-GT. Methodology/Principal Findings: Analyses were based on occupational health examinations of more than 15,000 German male workers aged 16–64 years, predominantly from the construction industry. Sociodemographics and other health-related information were collected during the exam. Joint associations of smoking and alcohol consumption or BMI with elevated or log-transformed γ-GT were examined by tabulation and multiple adjusted regression models. Cigarette smoking exerted no effect on γ-GT in teetotalers, but there was a statistically significant effect of smoking among participants with higher alcohol consumption intensity, odds of elevated γ-GT being increased by 24% and 27% per additional 10 cigarettes smoked per day in subjects drinking 61–90 and >90 gram alcohol per day, respectively (P for interaction = 0.039). The interaction was opposite for BMI, where no association was seen in obese subjects, whereas odds of elevated γ-GT were increased by 24% per 10 cigarettes below 25 kg/m2 (P for interaction = 0.040). This novel interaction was replicable in an independent cohort. Conclusion: The evidence for opposite interactions of smoking with alcohol and BMI as determinants of serum γ-GT suggests that different physiological pathways are responsible for the associations between these factors.