Carcinogenesis Advance Access published online on April 7, 2005
Carcinogenesis, doi:10.1093/carcin/bgi088
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1 Health Research Center, University of Utah, Salt Lake City, Utah 84108
* To whom correspondence should be addressed. Apolipoprotein E (apoE) plays a major role in the metabolism of bile acids, cholesterol, and triglycerides and has recently been proposed as being involved in the carcinogenic process. Given the potential role of bile acids in colorectal cancer etiology, it is reasonable that colorectal cancer risk might be modified by apoE genotype. We used data collected from a case-control study of colon cancer (n = 1556 cases and 1948 controls) and rectal cancer (n = 777 cases and 988 controls). Not having an e3 apoE allele significantly increased risk of colon cancer (OR 1.37 95% CI 1.00-1.87), particularly among those diagnosed when older than 64 years (OR = 1.88 95% CI 1.17, 3.04; p interaction between age and apoE genotype 0.05). A significant three-way interaction was detected for family history of colorectal cancer, age at diagnosis and apoE genotype (p = 0.05), with those diagnosed when older and not having an e3 allele having a significant increased risk with family history of colorectal cancer (OR 3.93 95% CI 1.23, 12.6). This compared with risk associated with family history of colorectal cancer among those diagnosed when older with an e3 allele of 1.61 (95% CI 1.17, 2.23) or those diagnosed when younger without an e3 allele (OR 2.40 95% CI 0.56-10.3). Among those diagnosed when older than 64, associations of BMI and prudent diet with colon cancer were stronger among individuals without an e3 allele, although the p for interaction was not significant. We did not detect any significant associations between apoE genotype and rectal cancer, survival after diagnosis with colorectal cancer, stage of disease at diagnosis, or type of tumor mutation. These findings suggest those apoE genotypes that do not include the e3 allele, the same genotypes that are associated with increased risk of coronary heart disease, may influence development of colon cancer among those who are older at diagnosis.
Received January 25, 2005
Revised March 11, 2005
Accepted March 25, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Associations between ApoE genotype and colon and rectal cancer
2 Fred Hutchinson Cancer Research Center, Seattle, Washington
3 Kaiser Permanente Medical Care Research Program
4 Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah
Martha L. Slattery, E-mail: mslatter{at}hrc.utah.edu
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