title: Interaction between Red Meat Intake and NAT2 Genotype in Increasing the Risk of Colorectal Cancer in Japanese and African Americans.
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.
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
authors.forename: Hansong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Iwasaki
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Suminori
authors.initials: S
authors.lastname: Kono
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.affiliation: Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Temitope O
authors.initials: TO
authors.lastname: Keku
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.affiliation: Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsugane
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
mesh_terms: D001741:Black or African American / Q000331:legislation & jurisprudence*; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000069466:Red Meat / Q000009:adverse effects*; D012307:Risk Factors; D014481:United States / Q000208:ethnology
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human