TY - JOUR
T1 - Red meat intake, NAT2, and risk of colorectal cancer
T2 - A pooled analysis of 11 studies
AU - Ananthakrishnan, Ashwin N.
AU - Du, Mengmeng
AU - Berndt, Sonja I.
AU - Brenner, Hermann
AU - Caan, Bette J.
AU - Casey, Graham
AU - Chang-Claude, Jenny
AU - Duggan, David
AU - Fuchs, Charles S.
AU - Gallinger, Steven
AU - Giovannucci, Edward L.
AU - Harrison, Tabitha A.
AU - Hayes, Richard B.
AU - Hoffmeister, Michael
AU - Hopper, John L.
AU - Hou, Lifang
AU - Hsu, Li
AU - Jenkins, Mark A.
AU - Kraft, Peter
AU - Ma, Jing
AU - Nan, Hongmei
AU - Newcomb, Polly A.
AU - Ogino, Shuji
AU - Potter, John D.
AU - Seminara, Daniela
AU - Slattery, Martha L.
AU - Thornquist, Mark
AU - White, Emily
AU - Wu, Kana
AU - Peters, Ulrike
AU - Chan, Andrew T.
N1 - Publisher Copyright:
© 2014 American Association for Cancer Research.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Background: Red meat intake has been associated with risk of colorectal cancer, potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and colorectal cancer has been inconsistently reported. Methods:Weused pooled individual-level data from the Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium. Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. Results: From 11 studies, 8,290 colorectal cancer cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of colorectal cancer compared with the lowest quartile [OR, 1.41; 95% confidence interval (CI), 1.29-1.55].However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with colorectal cancer in those with a rapid/intermediate NAT2 genotype (OR, 1.38; 95% CI, 1.20-1.59) as with a slow genotype (OR, 1.43; 95% CI, 1.28-1.61; P interaction = 0.9). Conclusion:Wefound that high red meat intake was associated with increased risk of colorectal cancer only from retrospective case-control studies and not modified by NAT2 enzyme activity. Impact: Our results suggest no interaction between NAT2 genotype and red meat intake in mediating risk of colorectal cancer.
AB - Background: Red meat intake has been associated with risk of colorectal cancer, potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and colorectal cancer has been inconsistently reported. Methods:Weused pooled individual-level data from the Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium. Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. Results: From 11 studies, 8,290 colorectal cancer cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of colorectal cancer compared with the lowest quartile [OR, 1.41; 95% confidence interval (CI), 1.29-1.55].However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with colorectal cancer in those with a rapid/intermediate NAT2 genotype (OR, 1.38; 95% CI, 1.20-1.59) as with a slow genotype (OR, 1.43; 95% CI, 1.28-1.61; P interaction = 0.9). Conclusion:Wefound that high red meat intake was associated with increased risk of colorectal cancer only from retrospective case-control studies and not modified by NAT2 enzyme activity. Impact: Our results suggest no interaction between NAT2 genotype and red meat intake in mediating risk of colorectal cancer.
UR - http://www.scopus.com/inward/record.url?scp=84921031196&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84921031196&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-14-0897
DO - 10.1158/1055-9965.EPI-14-0897
M3 - Article
C2 - 25342387
AN - SCOPUS:84921031196
VL - 24
SP - 198
EP - 205
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 1
ER -