Relationship among metabolizing genes, smoking and alcohol used as modifier factors on prostate cancer risk: Exploring some gene-gene and gene-environment interactions

Background: Prostate cancer (PCa) is one of the most common male cancers, but the burden of this disease shows remarkable worldwide variation. The role of susceptibility low penetrance genes and environmental factors in the etiology of (PCa) is unclear, but may involve, in some cases, multiple alleles at multiple loci and environmental factors. Study Objectives: To assess whether CYP1A1, GSTM1, GSTT1 susceptibility genotypes, smoking status and alcohol consumption factors contribute to PCa risk, gene-gene and gene-environment interactions were analyzed. Design and Participants: We explored interactions on a multiplicative scale conducting a population-based case-control and a case-only study on 103 incident PCa patients and 132 unrelated controls. Main Results: The interaction odds ratios (IOR) for PCa risk were increased in men who had both susceptibility genotypes GST (M1; T1) null and CYP1A1-M1* in a case-control and case-only design (IORcc: 1.11; 95% CI: 0.12-10.02; IORcc: 6.23; 95%, CI: 0.51-75.89; IORco: 2.80; 95% CI: 0.44-17.45 and IORco: 2.65; 95%, CI: 0.30-25.40). No clear evidence for interaction on a multiplicative scale between smoking status, alcohol consumption and genetic polymorphisms in PCa risk was observed. Conclusions: Our findings suggest that the interaction between genetic polymorphisms in GST (T1; M1) and CYP1A1-M1* would play a significant role as a modifying factor on PCa risk in Chilean people. However, these preliminary exploratory results should be confirmed in a larger study.This work was supported by the National Cancer Corporation of Chile (CONAC) and National Fund of Scientific Development FONDECYT Grant No. 3020043