The Health Outcome

Colorectal cancer is the third most common cancer in men and women and the second most common cause of cancer death in the United States (2).The American Cancer Society estimates that approximately 56,290 Americans will die of colorectal cancer in 2005, while 145,290 new cases will be diagnosed. The lifetime risk of developing colon or rectal cancer in the US is 5.9% for men and 5.5% for women. The overall incidence for all races/ethnicities was 63.4 per 100,000 for males and 46.4 per 100,000 for females, and the mortality rate for males was 25.3 per 100,000 and 17.7 per 100,000 for females from 1997-2001 (3). Incidence and mortality rates of colorectal cancer are higher among African Americans than other racial/ethnic groups.

As individuals age, the risk of developing colorectal cancer increases. Over 90% of cases occur in persons over the age of 50 (2). Other risk factors include a family and personal history of colorectal cancer, colorectal polyps, and inflammatory bowel disease. Several studies have shown that certain lifestyle factors may contribute to increased risk of colorectal cancer including lack of regular physical activity (4-6), being overweight or obese
(7-8), alcohol consumption, and tobacco use (2).

The Finding

The goal of the analysis stated by Slattery et al. was to determine if the associations between risk factors such as body mass index (BMI), physical activity, and energy intake, and colon and rectal cancer are affected by VDR genotype (1). The data came from two large population-based case-control studies of colon and rectal cancer. The participants were recruited from the Kaiser Permanente Medical Care Program of Northern California and the state of Utah. The first population, including 1174 cases and 1174 controls, came from a case-control study of colon cancer in which cases had a first primary colon cancer diagnosis between October 1, 1991 and September 30, 1994. The second population, including 785 cases and 1000 controls, came from a case-control study in which cases had a first primary tumor in the rectosigmoid junction or rectum identified between May 1997 and May 2001. The Bsm1, polyA, and Fok1 VDR polymorphisms were evaluated.

The major results of this study were as follows. First, obese individuals were at the greatest risk for colon cancer if they had the SS or BB (S and B alleles are in linkage disequilibrium) genotypes. Second, an increased risk of rectal cancer was associated with participants that reported low levels of physical activity and had the SL or Bb, LL or bb, or ff VDR genotypes. Third, those who were the least physically active and had the ff genotype were three times as likely to develop colon or rectal cancer. Finally, while there was no significant interaction between Bsm1 and polyA VDR genotypes and energy intake, there was evidence of interaction between the Fok1 VDR genotype, energy intake, and colon and rectal cancer.

The VDRff genotype increased the risk of colon cancer among study participants who were sedentary. The study results also indicated the VDRff genotype increased the risk for both colon and rectal cancer for those with high energy intake; however, the authors conclude that the association between energy intake and colon cancer appears to be driven more by energy intake than Bsm1 or polyA VDR genotypes.

The odds ratios of colon and rectal cancer due to VDR genotypes were at times protective, OR= 0.75 for obese individuals with the SS/BB genotype; at other times, the same SS/BB genotype led to an increased risk, OR=2.19 for high energy intake. As the authors state, “the fact that in some contexts these genotypes are protective and in other contexts they increase risk suggests the possibility that VDR may be acting through more than one pathway to influence carcinogenesis.” Perhaps these findings could ultimately help further our understanding of the physiological mechanisms associated with energy balance and cancer risk. Additional research on differences in association by VDR polymorphism could lead to discovery of the pathway and the mechanisms by which the VDR polymorphisms exert their effects.

References

1. Slattery M, et al. Associations between BMI, energy intake, energy expenditure, VDR genotype and colon and rectal cancers ( United States ). Cancer Causes and Control. 2004;15:863-872.
2. American Cancer Society. Cancer facts and figures, 2005. Atlanta, GA : American Cancer Society; 2005. Publication no. 5008.05.
3. Cancer Facts & Figures 2005, American Cancer Society, 2005.
4. Friedenreich C et al. Physical Activity and cancer prevention: etiologic evidence and biological mechanisms. J Nutr. 2002 Nov;132(11 Suppl):3456S-3464S.
5. Slattery M, et al. Physical activity and colon cancer: a public health perspective. Ann Epidemiology. 1997;7:137-145.
6. McTiernan A, et al. Physical activity and cancer etiology: associations and mechanisms. Cancer Causes and Control. 1995;9:487-509.
7. Calle E, et al. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med. 2003;348:1625-1638.
8. Hu, et la. Adiposity as compared with physical activity in predicting mortality among women. N Engl J Med. 2004;351:2694-2703.