10,11 The frequency of this putative rapid acetylator NAT1*10 allele is fairly common among African-Americans (50%).12 There is some evidence that inheritance of the NAT1*10 variant allele is associated with an increase in colo-rectal, breast and PCa relative to carriers of the homozygous NAT1*4/*4 genotype.13�C15 new Rare variant NAT1 alleles, such as NAT1*14B, *15, *17, *19, and *22 alleles, exhibit negligible levels of NAT1 protein expression and have lower catalytic activity toward N- hydroxylated heterocyclic amines. NAT1*3 and NAT1*11 are also rare variants. In particular, the NAT1*11 allele appears to be associated with elevated breast cancer risk; however, the acetylator phenotype among individuals carrying this marker is not completely understood.

16,17 Polymorphism in the NAT2 gene has led to the identification of a NAT2*4 (reference) and over 25 variant alleles.9 Several SNPs alone or in combination (eg, C282T, T341C, C481T, G590A, A803G, and G857A) result in NAT2 alleles (eg, NAT2*5, *6, *7, *14) with reduced activity and protein. However, polymorphism found in the NAT2*5 gene cluster resulted in the greatest reduction in N- and O-acetylation activity when compared to the reference genotype.18 Specifically, the T341C SNP targets the NAT2 protein for enhanced proteosomal degradation and is associated with the very slow NAT2 acetylator phenotype.19,20 Compared to rapid/intermediate acetylators, NAT2 slow acetylators had a 1.4-fold increase in bladder and prostate cancer risk that was stronger for cigarette smokers than for never smokers.

21,22 This increased risk is attributed to reduced capacity to detoxify N-hydroxylated aromatic amines in the liver and extrahepatic tissue, including the small intestine, bladder and prostate.23,24 The NAT1*10 and the slow NAT2 genotypes (individually and jointly) are suspected to increase PCa risk due to their affect on the metabolic activation of heterocyclic aromatic amines (via O-acetylation) in the prostate and/or decreased detoxification of aromatic amines (via N-acetylation) in the liver and prostate. In fact, Hein and co-workers (2002) observed a 5- and 7.5-fold increase in PCa susceptibility among individuals who possess the putative rapid NAT1*10 combined with the NAT2 slow (OR = 5.08; 95% CI: 1.56�C16.5; P = 0.008) or very slow NAT2 genotypes (OR = 7.50; 95% CI: 1.55�C15.4; P = 0.016), respectively.

15 However, additional studies are still warranted to clarify their role in susceptibility to PCa among men of African descent. Despite the striking prevalence Batimastat of PCa and the high frequency of NAT1*10 and slow NAT2 slow alleles among men of African descent, the phenotypic ramifications of polymorphic N- acetyltransferases remain understudied in this underserved subgroup. Hooker and co-workers (2008) evaluated 4 NAT2 SNPs (rs11120005, rs7832071, rs1801280, rs1799930) in relation to PCa susceptibility among participants of the current study.