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Int J Mol Epidemiol Genet 2012;3(2):96-106

Original Article
Polymorphisms in heterocyclic aromatic amines metabolism-related genes are
associated with colorectal adenoma risk

Monika Eichholzer, Sabine Rohrmann, Aline Barbir, Silke Hermann, Birgit Teucher, Rudolf Kaaks, Jakob Linseisen

Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, University of Zurich, Zurich,
Switzerland; Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; Institute of
Epidemiology I, Helmholtz Zentrum München, Neuherberg, Germany

Received April 4, 2012; accepted May 1, 2012; Epub May 15, 2012; Published May 30, 2012

Abstract: Colorectal adenoma (CRA) and colorectal cancer (CRC) risks have been linked to the intake of red and processed
meat. Heterocyclic aromatic amines (HCA) formed herein during high temperature cooking, are metabolized by a variety of
enzymes, and allelic variation in the coding genes could influence individual CRA risk. Associations of polymorphisms in NAT1,
NAT2, GSTA1, SULT1A1, CYP1A2, UGT1A7, UGT1A9, GSTP1 genes with colorectal adenoma risk were investigated in a
nested case-control study of the EPIC-Heidelberg cohort including 428 cases matched by age, sex and year of recruitment with
one or two controls (n=828) with negative colonoscopy per case. Genoyping was preformed with the Sequenom MassArray
system and the LightCycler 480. Conditional logistic regression was used to compute odds ratios (OR) and corresponding
95% confidence intervals (CI). For rs15561 (NAT1) and rs1057126 (NAT1), the rarer allel was significantly inversely associated
with adenoma risk OR=0.80 (95% CI 0.65-0.97) and (OR=0.81 (95% CI 0.65-0.99) and, respectively). For the combined NAT2
alleles encoding for enzymes with medium (versus slow) activity we also observed a significantly inverse association with
adenoma risk (OR=0.75; 95% CI 0.85-0.97). In addition, homozygous carriers of the A allele of rs3957357 (GSTA1), i.e., those
with a decreased enzyme activity, had a decreased risk of colorectal adenoma with an OR of 0.68 (95% CI 0.50-0.92; AA versus
GG/GA). Polymorphisms in the other tested genes did not modify the risk of colorectal adenomas. In conclusion,
polymorphisms in NAT1, NAT2, and GSTA1 are related to colorectal adenoma risk in this German cohort. (IJMEG1204003).

Key words: Colorectal adenoma, genetic polymorphisms, NAT1, NAT2, GSTA1


Address all correspondence to:
Dr. Sabine Rohrmann
Institute of Social and Preventive Medicine
Hirschengraben 84, 8002 Zürich, Switzerland.
Tel: +41 44 634 5256
E-mail: sabine.rohrmann@ifspm.uzh.ch