γ-Glutamyltransferase and cancer risk: The Korean cancer prevention study

Elevated serum γ-glutamyltransferase (GGT) is a marker of hepatic injury and is associated with risk of chronic disease. However, the value of GGT as a biomarker for cancer risk remains unclear. Therefore, we evaluated the association of serum GGT with cancer incidence among more than 1.6 million Koreans. We included 1,662,087 Koreans (1,108,121 men and 553,966 women aged 20-95 years) who received health insurance from the National Health Insurance Service and had a biennial medical evaluation between 1995 and 1998. Follow-up was through December 2012. Using Cox proportional hazards models, we adjusted for age, smoking status, alcohol consumption, exercise and body mass index after exclusion of early cases (cancer diagnosis or death within 5 years of starting follow-up) and estimated hazard ratios (HRs) of overall and organ-specific cancer incidence by GGT quintiles. During the 17-year follow-up, 129,087 new cancer cases occurred among the participants. Across levels of GGT, there was a positive gradient of HR and the highest quintile of GGT (≥60 IU/L) had the highest HR for all cancers in both men and women. By cancer site, the association was strongest for liver cancer, comparing the highest and lowest strata in men [HR, 6.67; 95% confidence interval (95%CI), 5.88-7.57] and in women (HR, 7.57; 95%CI, 6.41-8.94). Significant associations were also observed for cancers of the esophagus, larynx, stomach, colorectal, bile duct and lung in men and of the bile duct in women. Increased serum GGT level is independently associated with risk of cancer. What's new? Elevated serum γ-Glutamyltransferase (GGT) - a marker of hepatic injury that is associated with risk of chronic disease - is also a marker of oxidative stress and may thus be a useful risk indicator beyond traditional risk factors for cancer. Recent studies have, however, yielded conflicting results and focused on the Western population. In this large prospective Asian cohort study, elevated serum GGT was associated with overall cancer incidence, and with increased risk of liver and bile duct cancer specifically, in both men and women. The findings offer a comprehensive update and warrant further study into the possible underlying biological mechanisms.