Interaction between Red Meat Intake and NAT2 Genotype in Increasing the Risk of Colorectal Cancer in Japanese and African Americans

PLoS One. 2015 Dec 18;10(12):e0144955. doi: 10.1371/journal.pone.0144955. eCollection 2015.

Abstract

Heterocyclic aromatic amines formed in cooked meat may be an underlying mechanism for the red meat-colorectal cancer (CRC) association. These compounds require bioactivaction by N-acetyltransferase 2 (NAT2). An interaction effect between red meat consumption and NAT2 in increasing CRC risk has been inconsistently reported in whites. We investigated this interaction in two populations in which the high-activity rapid NAT2 phenotype is 10- and 2-fold more common than in whites. We meta-analyzed four studies of Japanese (2,217 cases, 3,788 controls) and three studies of African Americans (527 cases, 4,527 controls). NAT2 phenotype was inferred from an optimized seven-SNP genotyping panel. Processed and total red meat intakes were associated with an increased CRC risk in Japanese and in both ethnic groups combined (P's ≤ 0.002). We observed an interaction between processed meat intake and NAT2 in Japanese (P = 0.04), African Americans (P = 0.02), and in both groups combined (P = 0.006). The association of processed meat with CRC was strongest among individuals with the rapid NAT2 phenotype (combined analysis, OR for highest vs. lowest quartile: 1.62, 95% CI: 1.28-2.05; Ptrend = 8.0×10-5), intermediate among those with the intermediate NAT2 phenotype (1.29, 95% CI: 1.05-1.59; Ptrend = 0.05) and null among those with the slow phenotype (Ptrend = 0.45). A similar interaction was found for NAT2 and total red meat (Pinteraction = 0.03). Our findings support a role for NAT2 in modifying the association between red meat consumption and CRC in Japanese and African Americans.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • African Americans / legislation & jurisprudence*
  • Aged
  • Arylamine N-Acetyltransferase / genetics*
  • Asians / genetics*
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Red Meat / adverse effects*
  • Risk Factors
  • United States / ethnology

Substances

  • Arylamine N-Acetyltransferase
  • NAT2 protein, human