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Weighing the Evidence Linking UVB Irradiance, Vitamin D, and Cancer Risk–reply–I

      In reply: We agree with Dr Grant that evidence from ecological studies suggests that vitamin D may reduce cancer risk. Increasing distance from the equator is associated with increased risk of several cancers at a population level. However, one of the major limitations of ecological studies is referred to as the ecological fallacy, which is the error of making inferences at an individual level on the basis of aggregate population level data. It is entirely possible that a disease association found by comparing populations is absent, or even in the opposite direction, when individual level data are examined. Individuals in the population who develop cancer may not be those with low vitamin D status. In the case of ecological studies involving international cancer registries, many low-income countries are close to the equator and their cancer registries may be limited by the fact that many cancers are undiagnosed and underreported, resulting in a high likelihood of an ascertainment bias.
      • Valsecchi MG
      • Steliarova-Foucher E
      Cancer registration in developing countries: luxury or necessity?.
      Ecological studies are useful for generating hypotheses, but experimental studies and individual level data are necessary to ascertain causality.
      The association of reduced sunlight exposure at higher latitudes with increased cancer risk does not indicate that low vitamin D status causes increased cancer risk. Many confounding environmental and population variables are associated with both latitude and vitamin D exposure that can affect disease risk. For example, income, industrialization, temperature, water consumption, meat and fat intake, outdoor activity, obesity, and affective disorders are all associated with latitude and could be hypothesized to affect cancer risk apart from vitamin D status. Although vitamin D deficiency may be identified as a major risk factor for certain types of cancer or other diseases, experimental studies are needed to confirm this, in part because RCTs have failed to demonstrate the benefit of vitamin D supplementation for the prevention of breast and colon cancer.
      • Chlebowski RT
      • Johnson KC
      • Kooperberg C
      • et al.
      Calcium plus vitamin D supplementation and the risk of breast cancer.
      • Wactawski-Wende J
      • Kotchen JM
      • Anderson GL
      • et al.
      Calcium plus vitamin D supplementation and the risk of colorectal cancer.
      A large 5-year RCT of vitamin D supplementation currently under way may clarify the nonskeletal benefits of vitamin D, but the duration may be too short to establish its effect in long-latency diseases like cancer.
      • Manson JE
      • Buring JE
      • Brigham and Women's Hospital

      REFERENCES

        • Valsecchi MG
        • Steliarova-Foucher E
        Cancer registration in developing countries: luxury or necessity?.
        Lancet Oncol. 2008; 9: 159-167
        • Chlebowski RT
        • Johnson KC
        • Kooperberg C
        • et al.
        Calcium plus vitamin D supplementation and the risk of breast cancer.
        J Natl Cancer Inst. 2008; 100: 1581-1591
        • Wactawski-Wende J
        • Kotchen JM
        • Anderson GL
        • et al.
        Calcium plus vitamin D supplementation and the risk of colorectal cancer.
        N Engl J Med. 2006; 354: 684-696
        • Manson JE
        • Buring JE
        • Brigham and Women's Hospital
        Vitamin D and Omega-3 Trial (VITAL). National Library of Medicine, Bethesda, MDJanuary 26, 2011 (ClinicalTrials.gov Web site. http://clinicaltrials.gov/show/NCT01169259 Accessed February 1, 2011.)

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