Is environmental carcinogenesis modulated by host polymorphism?

Abstract

It is now clear that tobacco smoking, alcohol consumption, dietary factors and occupation can all interact with genetic host factors to place one individual at a greater or lesser risk of a particular cancer than another. Phenotypes which confer significantly elevated risks arise from the human CYP1A1. CYP2D6, GST1 and NAT (N-acetyltransferase) genes. The last is the only one remaining to be cloned. It is envisaged that several of these genes may interact in a given circumstance cooperatively to increase susceptibility. For example CYP1A1, CYP2D6 and GST1 genotypes may have additive or multiplicative risks of bronchogenic carcinoma in cigarette smokers. CYP2D6 and NAT genotypes may interact in bladder cancer. The advent of molecular genetics brings us closer to the day when, for example, factory workers in potentially hazardous environments might be screened using PCR methodology on skin scrapings or buccal swabs for their innate susceptibility to combined workplace and lifestyle cancer risks.