American Journal of Epidemiology Advance Access originally published online on March 15, 2008
American Journal of Epidemiology 2008 167(8):1016; doi:10.1093/aje/kwn040
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LETTERS TO THE EDITOR |
RE: "BODY SIZE, WEIGHT CYCLING, AND RISK OF RENAL CELL CARCINOMA AMONG POSTMENOPAUSAL WOMEN: THE WOMEN'S HEALTH INITIATIVE (UNITED STATES)"
1 Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892
2 Cancer Stem Cell Section, Laboratory of Cancer Prevention, and Center for Cancer Research, National Cancer Institute, Frederick, MD 21702
(e-mail: galanthus7{at}yahoo.com)
Luo et al. (1) recently showed that central adiposity may largely account for the link between obesity and the risk of renal cell carcinoma. The possible biologic mechanisms of this link discussed in their article include elevated levels of insulin, insulin-like growth factor-1, and sex steroids. However, we believe an additional important mechanistic possibility is chronic hypoxia. Genetic syndromes that predispose to renal cell carcinoma, such as the von Hippel-Lindau (VHL) syndrome, and some epidemiologic risk factors both lead to perturbations in hypoxia detection (2), which may be a common link in causing renal cell carcinoma. These mechanisms may all reflect the kidney's physiologic mechanism of hypoxia detection that has gone awry. VHL is physiologically involved in hypoxia detection, leading to an increase in erythropoietin production and an increase in red blood cell production (3). Chronic hypoxia may lead to a similar tumorigenic mechanism as VHL mutations, in oxygen-detecting tissues, such as the kidney. In addition to the metabolic changes noted by Luo et al., obesity can lead to chronic hypoxia through sleep apnea. Furthermore, central adiposity, in particular, predisposes to sleep apnea (4, 5), which may explain the findings of Luo et al. Although our hypothesis is speculative, we believe that the potential link between sleep apnea, as well as other causes of chronic hypoxia, and renal cell carcinoma merits epidemiologic study.
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- Luo J, Margolis KL, Adami HO, et al. Body size, weight cycling, and risk of renal cell carcinoma among postmenopausal women: the Women's Health Initiative (United States). Am J Epidemiol (2007) 166:752–9.
[Abstract/Free Full Text] - Sharifi N, Farrar WL. Perturbations in hypoxia detection: a shared link between hereditary and sporadic tumor formation? Med Hypotheses (2006) 66:732–5.[CrossRef][Web of Science][Medline]
- Kaelin WG Jr. The von Hippel-Lindau gene, kidney cancer, and oxygen sensing. J Am Soc Nephrol (2003) 14:2703–11.
[Abstract/Free Full Text] - Vgontzas AN, Papanicolaou DA, Bixler EO, et al. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab (2000) 85:1151–8.
[Abstract/Free Full Text] - Grunstein R, Wilcox I, Yang TS, et al. Snoring and sleep apnoea in men: association with central obesity and hypertension. Int J Obes Relat Metab Disord (1993) 17:533–40.[Web of Science][Medline]
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  K. L. Margolis, J. Luo, W. Ye, H.-O. Adami, and for the Women's Health Initiative Investigators FOUR AUTHORS REPLY Am. J. Epidemiol., April 15, 2008; 167(8): 1016 - 1016. [Full Text] [PDF]
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