Elsevier

The Journal of Nutrition

Volume 135, Issue 2, February 2005, Pages 179-186
The Journal of Nutrition

Nutrient-Gene Interactions
The CYP1A1 Genotype May Alter the Association of Meat Consumption Patterns and Preparation with the Risk of Colorectal Cancer in Men and Women1

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ABSTRACT

We hypothesized that the risk of colorectal cancer associated with meat preparation methods producing heterocyclic amines or polycyclic aromatic hydrocarbons is modified by the CYP1A1 genotype alone or in combination with the GSTM1 genotype or the NAT2 imputed phenotype. A total of 952 rectal cancer cases and 1205 controls (between September 1997 and February 2002) and 1346 colon cancer cases and 1544 controls (between October 1991 and September 1994) from Utah and Northern California were recruited from a population-based case-control study. Detailed interviews ascertained lifestyle, medical history, and diet and we extracted DNA from whole blood. Risk of colorectal cancer decreased among men with the CYP1A1 *2 any variant genotype and the lowest intake of poultry and men and women with high use of white meat drippings. Risk increased among men with the CYP1A1 *1 (no variant) allele and high white meat mutagen index, but decreased among those with the CYP1A1 *2 genotype. Risk increased with a high white meat mutagen index among women with the CYP1A1 *2 genotype and the GSTM1 present genotype. Risk of colorectal cancer decreased with the CYP1A1 *2 genotype, the NAT2 slow phenotype, and the use of white meat or its drippings. The association of risk for colorectal cancer and selected red and white meat mutagen indices and the use of white meat drippings, or fried white meat variables was more evident within select combinations of the CYP1A1 genotype and either the GSTM1 genotype or NAT2 than with the CYP1A1 alone. Genetic susceptibility may modify the associations of some meat or meat preparation factors with the risk of colorectal cancer.

Key Words

rectal cancer
meat
CYP1A1
NAT2
GSTM1

Abbreviations

A
adenine
bp
base pair
CYP
cytochrome p-450
C
cytosine
G
guanine
GST
glutathione S-transferase
HCA
heterocyclic amine
KPMCP
Kasier Permantente Northern California Cancer Registry
NAT
N-acetyl transferase
PAH
polycyclic aromatic hydrocarbon
PCR
polymerase chain reaction
T
thymine

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1

This study was funded by CA48998 and CA85846 to Dr. Slattery and the Utah Cancer Registry, which is funded by Contract No. N01-PC-67000 from the National Cancer Institute, with additional support from the State of Utah Department of Health, the Northern California Cancer Registry, and the Sacramento Tumor Registry. The contents are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute.