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Red meat intake, CYP2E1 genetic polymorphisms, and colorectal cancer risk
Loïc Le Marchand1, Timothy Donlon, Ann Seifried
1Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii 96813, USA.
Summary
N-Nitroso compounds in red and processed meats may increase rectal cancer risk. A specific CYP2E1 gene variant amplifies this risk, particularly for individuals with high meat consumption.
Area of Science:
- Genetics
- Gastroenterology
- Oncology
Background:
- N-Nitroso compounds are suspected carcinogens linked to colorectal cancer (CRC).
- High consumption of red meat (RM) and processed meat (PM) increases exposure to these compounds.
- CYP2E1 enzyme metabolizes N-Nitroso compounds, and its genetic variations may influence CRC susceptibility.
Purpose of the Study:
- To investigate the association of two functional CYP2E1 polymorphisms with CRC risk.
- To examine the modifying effect of these polymorphisms on the association between RM/PM intake and CRC.
- To assess CRC risk in relation to dietary factors and CYP2E1 variants.
Main Methods:
- A population-based case-control study in Hawaii.
- Inclusion of 521 CRC patients and 639 controls of diverse ethnic backgrounds.
- Genotyping for CYP2E1 G1259C and 5' 96-bp insertion variants using PCR.
Main Results:
- The CYP2E1 5' insert variant was associated with a 60% increased risk of rectal cancer.
- Individuals with the insert variant and high RM/PM intake showed a 2- to 3-fold increased risk for rectal cancer.
- No significant association was observed for colon cancer; however, increased rectal cancer risk was noted with salted fish and pickled vegetable consumption.
Conclusions:
- Nitrosamines may be carcinogenic to the human rectum.
- RM and PM are significant sources of nitrosamine exposure.
- CYP2E1 genetic variants may play a role in rectal cancer susceptibility, particularly with specific dietary exposures.