Genetic susceptibility, biomarker respones, and cancer.

摘要: Abstract A large number of studies have reported associations between polymorphisms xenobiotic-metabolizing enzymes (XMEs) and various cancers. However, the carcinogenic exposures behind such findings usually been unclear. Information on susceptibility to specific carcinogens could better be obtained by examining situations where exposure endpoint studied are nearer in time, i.e., studying biomarkers carcinogen early (genotoxic) effect exposed humans. For example, analyses DNA adducts cytogenetic endpoints indicated an increased glutathione S -transferase M1 ( GSTM1 ) null genotype genotoxicity tobacco smoking, supporting view that with bladder lung cancer partly related smoking. In vitro human cells offer experimental tool can used, within limits cell systems, predict individual sensitivity genotype–carcinogen interactions. 1,2:3,4-diepoxybutane, epoxide metabolite 1,3-butadiene has clearly shown depend GSTT1 genotype, which also implicated modify, along 1,2-epoxy-3-butene, another 1,3-butadiene. These genotypes appear modulate excretion 1,3-butadiene-specific mercapturic acids, influence biomarker levels 1,3-butadiene-exposed workers. The acids (PHEMA) workers styrene seems one PHEMA diastereoisomer. styrene. general, genetic potentially important for response largely exposing agent, biological material examined, ethnicity population under study. Individual level may vary a lot, reliable estimate is essential correct interpretation genotype–exposure interaction. Besides XME polymorphisms, any affect cellular damage could, principle, modify genotoxins. instance, those concerning repair proteins presently being many laboratories.