Genetic Susceptibility Genes

A relatively new area of cancer genetics has emerged, involving exploring the question of genetic susceptibility (i.e., given the same level of exposure, why are only certain individuals at risk?). Several genes important in the detoxification of chemical carcinogens are polymorphic in the population, with certain variants resulting in a reduced capacity to metabolize carcinogens; these individuals may be at a higher risk of developing cancer.102 Recent studies have explored whether the germline absence of certain genes (e.g., glutathione-S transferase M1, T1), as well as possession of genes that may provide less capability of detoxification (e.g., slow N-acetyltransferase-2 (NAT2) genotype, GSTPi valine variant), may be important risk factors for childhood acute leukemia. Davies et al.,103 in a molecular study of 232 White children with AML, found an overrepresen-tation of the GSTM1 null genotype among cases with M3 (82 percent) and M4 (72 percent) myeloid leukemia when compared to population controls (47 percent). Another study by Krajinovic et al.104 of 176 children with ALL reported a higher frequency of the NAT2 slow acetylation genotype when compared to 306 healthy controls (OR = 1.5, 95 percent CI = 1.0 to 2.2). This same group had previously reported a higher frequency of the GSTM1 null genotype and CYP1A1*2A genotype among cases compared with controls.105 Infante-Rivard et al.106 recently explored gene-environment interactions in 123 children with ALL and found a statistically significant interaction between specific pesticide exposures and the CYP1A1m1 and CYP1A1m2 genotypes. These explorations of gene-gene and gene-environment interactions may be very important. One of the difficulties in conducting these studies, however, is the potential lack of statistical power due to diminishing numbers of cases in stratified cells. With the additional power of meta-analyses (statistically combining results of studies on the same topic), characterization of genotypes that may be important in the development of childhood leukemia is possible.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

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