May 29, 2003 Access past issues

Reviewed by: Lily Nguyen, MSPH Department of Epidemiology Rollins School of Public Health Emory University

The Health Outcome

Colorectal cancer is the second leading cause of cancer-related death in the United States and accounts for about 11% of all cancer-related deaths. In 2003, an estimated 147,500 new cases will be diagnosed, and 57,100 deaths from colorectal cancer will occur [1]. The 5-year relative survival rate is 90% for people whose colorectal cancer is treated in an early stage, but only 37% of cases are found early. Risk does not differ between men and women, but it does increase by age 40, rises sharply at 50-55, and then doubles with each following decade. Colorectal cancer has an incidence rate of 54 per 100,000 and a death rate of 22 per 100,000, but both rates vary by racial/ethnic group [2].

About 25% of colorectal cancer patients have a family history of colorectal cancer. The two major forms of hereditary colorectal cancer involve APC and mismatch repair gene mutations [3]. Research in sporadic cases has involved polymorphisms of genes involved with the metabolism of carcinogens, including glutathione S-transferase (GST), cytochrome P450 (CYP450), and acetyltransferase (NAT1, NAT2).

The Finding Le Marchand et al. [4] reported that variants of the CYP2E1 cytochrome gene increased the risk for colon or rectal cancer and that an interactive effect with consuming meats increased this risk. This information was found in a case-control study conducted among residents of Hawaii that included 548 persons with colon or rectal cancer and 656 healthy controls. Genotyping for the RsaI and 96-bp insertion polymorphisms was completed for nearly all participants. No association was found between c1 (RsaI+) variants and colorectal cancer. The insertion variant, which confers high CYP2E1 activity, was associated with a 60% increased risk for colorectal cancer. Individuals carrying the insert and had higher intake of red and processed meats were at a twofold and threefold greater risk, respectively, for colorectal cancer.

Public Health Implications

Although this is a novel finding, potential problems exist with selection bias that may have influenced the statistical significance of the results. Another concern is that alcohol consumption, an inducer of CYP2E1, was not controlled for in the analyses.

This is the first report to address interactive effects of CYP2E1 and meat consumption in relation to colorectal cancer. Studies have established the link between meat consumption and colorectal cancer [5] and that of nitrosamine exposure from protein metabolism and colorectal cancer [6]. Increased nitrosamine concentration has also been linked to production of mutagens after activation by CYP2E1 [7]. Thus, the authors’ tentative findings are biologically plausible and merit further research.

Several polymorphisms in CYP2E1 have been characterized, but little has been done in regard to interaction with diet and related dose-response effects. New studies should consider confounding by exposures to compounds metabolized by CYP2E1, such as tobacco use, alcohol intake, and anti-inflammatory drugs [8].

References

1. American Cancer Society. Cancer Facts and Figures 2003. Atlanta, GA: American Cancer Society, 2003.
2. National Cancer Institute. Racial/Ethnic Patterns of Cancer in the United States 1988-1992. Bethesda, MD: National Cancer Institute, 1996. (NIH Pub. No. 96-4104).
3. Calvert PM, Frucht H. The genetics of colorectal cancer. Ann Intern Med  2002; 137(7):603-12.
4. Le Marchand L, Donlon T, Seifried A, et al. Red meat intake, CYP2E1 genetic polymorphisms, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 2002;11(10):1019-24.
5. Norat T, Lukanova A, Ferrari P, et al. Meat consumption and colorectal cancer risk: dose-response meta-analysis of epidemiological studies. Int J Cancer 2002;98(2):241-56.
6. Knekt P, Jarvinen R, Dich J, et al. Risk of colorectal and other gastro-intestinal cancers after exposure to nitrate, nitrite, and N-nitroso compounds: a follow-up study. Int J Cancer 1999; 80:852-86.
7. Rannug A, Alexandrie AK, Persson I, et al. Genetic polymorphism of cytochromes P450 1A1, 2D6 and 2E1: regulation and toxicological significance. J Occup Environ Med 1995;37(1):25-36.
8. Potter JD, Slattery ML, Bostick RM, et al. Colon cancer: a review of the epidemiology. Epidemiol Rev 1993;15(2):499-545.