Analysis of NAT2 coding variants, combined genotypes, and haplotypes in prostate cancer susceptibility: a case-control study in an Iraqi Arab population.

Authors

Murtadha A Tarish, Bassam K Kudhair

Published in

Molecular biology reports. Volume 53. Issue 1. Sep 27, 2026. Epub Sep 27, 2026.

Abstract

Genetic variation in the xenobiotic-metabolizing enzyme N-acetyltransferase 2 (NAT2) may modify individual susceptibility to prostate cancer (PCa); however, findings across populations remain inconsistent. This study investigated the association between NAT2 polymorphisms and PCa risk in an Iraqi Arab population.
A total of 97 patients with histologically confirmed prostate adenocarcinoma and 100 healthy controls were enrolled. NAT2 polymorphisms were identified by PCR and bidirectional Sanger sequencing.
Five NAT2 polymorphisms (c.282 C > T; c.341T > C; c.481 C > T; c.590G > A; and c.803G > A) were analyzed. Variant genotypes generally showed a trend toward a reduced risk of PCa. Under the allelic model, the minor allele of c.590G > A was nominally associated with reduced PCa risk (OR = 0.63, 95% CI: 0.41-0.97; p = 0.036, q = 0.108), while the dominant model showed a borderline protective association for carriers of the A allele (GA + AA) (OR = 0.59, 95% CI: 0.34-1.04; p = 0.07, q = 0.21). Linkage disequilibrium analysis identified strong correlations between c.282 C > T and c.590G > A, and between c.341T > C and c.481 C > T. Combined genotype analysis suggested a potential protective effect among carriers of variant alleles at both c.590G > A and c.803G > A (OR = 0.52, 95% CI: 0.25-1.08; p = 0.08, q = 0.24). Haplotype analysis identified NAT2*6A (TTCAA) as nominally significantly associated with reduced PCa risk (OR = 0.34, 95% CI: 0.13-0.88; p = 0.025, q = 0.13). No significant associations were observed for NAT2 c.341T > C, NAT2*5B-, or NAT2*6 C-defining variants.
The NAT2*6A haplotype was associated with reduced PCa risk among Iraqi Arabs; although this did not survive correction for multiple testing, it suggests a possible association warranting validation in larger, independent cohorts. Whether NAT2-mediated bioactivation of procarcinogens contributes to prostate carcinogenesis remains to be established.

PMID:
42801388
Bibliographic data and abstract were imported from PubMed on 28 Sep 2026.

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