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.
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Authors | Hansong Wang, Motoki Iwasaki, Christopher A Haiman, Suminori Kono, Lynne R Wilkens, Temitope O Keku, Sonja I Berndt, Shoichiro Tsugane, Loïc Le Marchand |
Journal | PloS one
(PLoS One)
Vol. 10
Issue 12
Pg. e0144955
( 2015)
ISSN: 1932-6203 [Electronic] United States |
PMID | 26683305
(Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Arylamine N-Acetyltransferase
- NAT2 protein, human
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Topics |
- Black or African American
(legislation & jurisprudence)
- Aged
- Arylamine N-Acetyltransferase
(genetics)
- Asian People
(genetics)
- Colorectal Neoplasms
(etiology, 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)
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