Interactions between detoxifying enzyme polymorphisms and susceptibility to cancer.

摘要: Many case-control studies on the role of detoxifying enzyme polymorphisms in susceptibility to cancer have identified significant associations, though few effects with sufficient strength be useful clinically. Odds ratios 2-3 are usual finding. Therefore, combinations risk alleles increasingly studied hope identifying haplotypes biological impact (odds ratio > 15) warrant further study a clinical setting. The interactions between different loci should based sense, for example classical view two-step xenobiotic detoxification, overlapping substrate specificities, detoxification molecules derived from same pathological insult (e.g. nitrosamines and polycyclic aromatic hydrocarbons cigarette smoke) or simultaneous regulation expression. rationale behind these mechanisms is discussed. Considerable amounts data focused interaction CYP1A1 GSTM1, particularly Japanese patients lung cancer. In this regard there accumulating evidence suggesting that combination GSTM1 null/CYP1A1 rare alleles, smoking, confers highly increased risk. However, now some debate importance terms chemical detoxificatlon, since certain suggest been investigated do not influence function expression gene. Indeed, CYP2D6 genetic variation also disputed, may acting more as linkage markers than by influencing carcinogenesis themselves. What clear many comparative lack supporting synergism genes. Given inevitable increase complexity studies, basic explanation statistical approaches assessment included chapter. A detailed statistical/epidemiological given elsewhere book. Since an increasing reluctance journals publish describing (usually moderate) polymorphisms, it important scientists understand what approach appropriate address issue novel clinically angle. This likely involve multiple genes subgroup analysis kind.