Affiliations of authors: A. Hsing, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; S. Chua Jr., Division of Molecular Genetics, Department of Pediatrics, Columbia University, New York, NY.
Correspondence to: Ann Hsing, Ph.D., National Cancer Institute, National Institutes of Health, Division of Cancer Epidemiology and Genetics, EPS-7058, MSC-7234, 6120 Executive Blvd., Bethesda, MD 20852-7234 (e-mail: hsinga{at}mail.nih.gov).
We agree with Drs. Stattin and Kaaks that our earlier findings associating abdominal obesity, hyperinsulinemia, and insulin resistance with prostate cancer risk in Chinese men with a relatively low body mass index (BMI; average BMI = 21 kg/m2) cannot be readily extrapolated to Western men and that these associations need to be replicated in prospective studies and other populations. In their nested casecontrol study of Swedish men, Drs. Stattin and Kaaks showed no association between insulin resistance and prostate cancer risk. They pointed out that a number of factors, including differences in study design, clinical characteristics of case subjects, selection of control subjects, prevalence of overall and abdominal obesity, and genetic susceptibility, could contribute to the differences in findings between their study and ours. Because of the much higher average BMI in the Swedish study (average BMI = 26 kg/m2) and the small number of case subjects, it was difficult to restrict the analysis to men with a BMI below 25 kg/m2 (the cutoff for overweight) or even lower, which would have yielded results more comparable to ours. In addition, among overweight or obese individuals, it may be more difficult to detect the effect of insulin resistance because of potential changes in their metabolic profiles.
Although the evidence for a role of overall obesity (measured by BMI) in prostate cancer is not conclusive, data in the literature generally suggest a link between obesity and more aggressive and advanced prostate tumors (1). Recently, a large prospective study of more than 400 000 U.S. men and 4004 prostate cancer deaths reported a 34% excess prostate cancer risk among men in the highest quartile of BMI (>35 kg/m2), relative to those in the lowest quartile (2). These results further support the obesityprostate cancer hypothesis.
It is possible that abdominal obesity may play a more important role in prostate cancer than overall obesity, and differences in the prevalence of abdominal obesity and genetic susceptibility between Asian and Western men may partially explain the differences in study findings. Although Chinese men are generally considered to be relatively lean (only 4% had a BMI >30 kg/m2 in our study), 24% of our study subjects had abdominal obesity (as measured by a waist-to-hip ratio >0.90) (3), and a small subset were considered to be metabolically obese (individuals with insulin resistance despite having a normal weight) (4). Asian men, in particular Southeast Asians and Asian Indians, despite their much lower BMI, are much more prone to develop insulin resistance than Caucasian men (5). In a study of African and Hispanic American men in the Bronx, we reported that a polymorphism of the insulin gene (INS) is associated with prostate cancer; men without diabetes but harboring the homozygous CC genotype of +1127 INS-PstI have a threefold increased risk of prostate cancer (6). Whether Asian men with certain genetic predispositions are at higher risk of developing prostate cancer is currently unclear and needs to be elucidated further.
Given the rising global epidemic of obesity and the high morbidity of prostate cancer, the role of obesity and insulin resistance needs to be clarified in large prospective studies with high-quality exposure assessment. Such studies should be large enough to permit testing of the obesity hypothesis and, at the same time, take into account the effect of other factors, such as physical activity, energy balance, insulin-like growth factors, sex hormones, and genetic susceptibility. These studies will help us to achieve a better understanding of the overall picture of prostate cancer etiology and the complex interplay between lifestyle and genetic factors.
REFERENCES
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3 Hsing AW, Deng J, Sesterhenn IA, Mostofi FK, Stanczyk FZ, Benichou J, et al. Body size and prostate cancer: a population-based case-control study in China. Cancer Epidemiol Biomarkers Prev 2000;9:133541.
4 Goodpaster BH, Krishnaswami S, Resnick H, Kelley DE, Haggerty C, Harris TB, et al. Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care 2003;26:3729.
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6 Ho GY, Melman A, Liu SM, Li M, Yu H, Negassa A, et al. Polymorphism of the insulin gene is associated with increased prostate cancer risk. Br J Cancer 2003;88:2639.[CrossRef][ISI][Medline]
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