© The Author 2006. Published by Oxford University Press.
CORRESPONDENCE |
RESPONSE: Re: Diabetes Mellitus and Risk of Colorectal Cancer in the Singapore Chinese Health Study
Affiliations of authors: Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore (AS, WPK, HPL); The Cancer Center, University of Minnesota, Minneapolis, MN (JMY, MCY)
Correspondence to: Adeline Seow, MD, Department of Community, Occupational and Family Medicine, National University of Singapore, MD3, 16 Medical Drive, Singapore 117597, Singapore (e-mail: cofseowa{at}nus.edu.sg).
We thank Dr. Wong for her comments about our study. She points out that preventing diabetes is likely to have a small impact on the incidence of colorectal cancer in Singapore, the population attributable risk (PAR) being about 5.7%. The size of this PAR is a result of both the modest size of the effect (an approximately 50% increase in risk of colorectal cancer associated with a history of diabetes) and the low prevalence of self-reported diabetes due to its underdiagnosis in the study population (1). This under-reporting leads to an underestimate of the PAR (2) and not to an overestimate, as asserted.
The PAR provides an estimate of the proportion of cases that would be prevented if a causal exposure is removed from the population (3). In our study hypothesis and in the interpretation of our results, we considered diabetes mellitus to be a surrogate marker for insulin resistance and for hyperinsulinemia. We believe that high levels of insulin and insulin-like growth factors play an etiologic role in the development of colorectal cancer, a view that is gaining increasing support from experimental and epidemiologic data (4,5).
Insulin resistance, which is primarily due to energy imbalance, physical inactivity, and consequent visceral adiposity (as evidenced by a high waist-to-hip ratio), is a prevalent condition, and diabetes mellitus is the most overt clinical manifestation of this phenomenon. Whereas 8.2% of adult Singapore residents have diabetes mellitus, a further 12% have demonstrable impaired glucose tolerance (1). The metabolic syndrome, a cluster of coronary risk factors that are linked by insulin resistance (6), is present in 23% of U.S. men and women (7). The aim of prevention, then, lies not in targeting diabetes mellitus in particular but in targeting the potentially modifiable lifestyle factors that lead to insulin resistance. If our understanding of the causal pathways is correct, these efforts will impact the incidence of a wide range of conditions, including colorectal cancer and cardiovascular disease. Large-scale epidemiologic studies with more proximate measures of insulin resistance will be needed to better estimate the potential impact of these interventions.
REFERENCES
(1) Epidemiology and Disease Control Department, Ministry of Health, Singapore. National Health Survey 2004 (report). Singapore (Singapore): Ministry of Health; 2005.
(2) MacMahon B, Trichopoulos D. Epidemiology principles and methods. 2nd ed. Boston (MA): Little, Brown and Company; 1996. p. 294.
(3) Rothman KJ, Greenland S. Modern epidemiology. 2nd ed. Philadelphia (PA): Lippincott-Raven; 1998. p. 295.
(4) Giovannucci E. Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr 2001;131:3109S–3120S.
(5) Wei EK, Ma J, Pollak MN, Rifai N, Fuchs CS, Hankinson SE, et al. A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women. Cancer Epidemiol Biomark Prev 2005;14:850–5.
(6) Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005;365:1415–28.[CrossRef][ISI][Medline]
(7) Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome. Prevalence and associated risk factor findings in the US population form the Third National Health and Nutrition Examination Survey, 1988–1994. Arch Intern Med 2003;163:427–36.
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J Natl Cancer Inst 2006 98: 1019.
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