IJE Advance Access originally published online on December 14, 2005
International Journal of Epidemiology 2006 35(2):231-232; doi:10.1093/ije/dyi292
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Commentary |
Commentary: Seeing the light
School of Public Health, Edward Ford Building A27, The University of Sydney, NSW 2006, Australia. E-mail: brucea{at}health.usyd.edu.au
Cedric and Frank Garland1 observed that metropolitan states in the south-west of the US had lower mortality rates from colon cancer in 1959–61, on average 
10 per 100 000 per year age-adjusted in white males, than metropolitan states in the north-west, on average 15 per 100 000. They reported that the rank order coefficient of correlation between colon cancer mortality and solar irradiance across the metropolitan states was –0.7. It was –0.6 across non-metropolitan states and the same values were obtained when cancer mortality rates for US counties in 1950–69 were used instead of the whole-of-state values. They noted, from broad regional data, that the probably mainly south to north gradient in colon cancer mortality did not appear to correlate well with patterns of dietary meat, fruit, or vegetable intake but acknowledged that its correlation with solar irradiance might still be due to confounding with some other dietary, behavioural, or, perhaps, genetic factor.
Apperly2 had reported an association between mortality from all cancers and solar irradiance across the states of the US 40 years earlier and suggested ‘it may be possible to reduce our cancer deaths by exposing suitable skin areas to sunlight ... insufficient to cause skin cancer’. While the Garlands did not acknowledge this work they can be reasonably excused for not having uncovered it.
Unsurprisingly, the Garlands advanced the possibility that photolytic production of vitamin D in the skin might explain the correlation between colorectal cancer mortality and solar irradiance. This is the major source of vitamin D for most human populations. They advanced an argument about anti-inflammatory effects of calcium (the absorption of which is promoted by vitamin D) in the bowel mucosa and evidence of a protective effect of milk against colon cancer in one US study (milk was and is mandatorily fortified with vitamin D in the US) in support of this possibility.
The Garlands and others published papers reporting on correlations in the US between solar irradiance and cancers of the breast,3 prostate,4 and ovary5 over the subsequent decade or so. None of these, or the original paper on colon cancer, initially attracted much attention. Indeed, the International Agency for Research on Cancer's 1992 monograph on the carcinogenic risk of solar and ultraviolet radiation to humans stated that ‘no adequate data were available to the Working Group’ when referring to all cancers other than skin, lip, and ocular cancers.6 The Garland's papers on breast and colon cancer were evaluated by the Group, of which I was a member, but considered to be of little evidentiary value because they were geographical correlation studies.
The Garlands, however, successfully pursued their hypothesis that a protective effect of vitamin D might underlie the inverse association they observed between colon cancer mortality and solar irradiance and stimulated the conduct of analyses of the associations between colon cancer mortality and, respectively, dietary vitamin D intake and plasma vitamin D in subjects in the Western Electric Health Study and the Washington County, Maryland, cohort study. Both analyses suggested that vitamin D was strongly protective against colon cancer.7,8 A recent review has assessed the evidence for a protective effect of vitamin D per se against cancer as substantial for colorectal cancer, inconsistent for prostate cancer, and ‘too sparse to support a conclusion’ for breast cancer.9 Thus for colorectal cancer at least, the Garland's work initiated a valuable research direction, although not yet exploited for cancer prevention.
That sun exposure, whether mediated by vitamin D or not, might have protective effects against cancer was not explored further, except by way of additional, broad geographical correlation studies, until the papers of Luscombe et al.10 in 2001 and Freedman et al.11 in 2002. The former observed a strong inverse association between recalled personal sun exposure and risk of prostate cancer, which has since been confirmed by a second, essentially identical study by the same investigators.12 The latter found inverse associations of occupational sun exposure, evaluated from job title, with colon and breast cancers but not with prostate or ovarian cancers.
Subsequently, and unexpectedly (because the opposite was hypothesized) an apparently strong protective effect of sun exposure has been observed against non-Hodgkin lymphoma,13 and since confirmed,14 and sun exposure has been reported to improve survival after a diagnosis of cutaneous melanoma, independently of efforts at earlier diagnosis.15 What an irony! Variation in survival with season of diagnosis has also been reported for cancers of the breast, colon, and prostate, cutaneous melanoma and Hodgkin lymphoma.16–18
The worms are at last wriggling out of the can that the Garlands opened 25 years ago.
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1 Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol 1980;9:227–31. (Reprinted Int J Epidemiol 2006;35:217–20.)
2 Apperly FL. The relation of solar radiation to cancer mortality in North America. Cancer Res 1941;1:191–95.
3 Garland FC, Garland CF, Gorham ED, Young JF. Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med 1990;19:614–22.[CrossRef][Web of Science][Medline]
4 Hanchette CL, Schwartz GG. Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation. Cancer 1992;70:2861–69.[CrossRef][Web of Science][Medline]
5 Lefkowitz ES, Garland CF. Sunlight, vitamin D and ovarian cancer mortality rates in US women. Int J Epidemiol 1994;23:1133–36.
6 International Agency for Research on Cancer. Solar and Ultraviolet Radiation. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 55. Lyon: International Agency for Research on Cancer, 1992.
7 Garland C, Shekelle RB, Barrett-Connor E, Criqui MH, Rossof AH, Paul O. Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospetive study in men. Lancet 1985;1:307–09.[CrossRef][Web of Science][Medline]
8 Garland CF, Garland FC, Comstock GW, Helsing KJ, Shaw EK, Gorham ED. Serum 25-hydroxyvitamin D and colon cancer: eight year prospective study. Lancet 1989;2:1176–78.[Web of Science][Medline]
9 Giovannucci E. The epidemiology of vitamin D and cancer incidence and mortality: A review. Cancer Causes Control 2005;16:83–95.[CrossRef][Web of Science][Medline]
10 Luscombe CJ, Fryer AA, French ME et al. Exposure to ultraviolet radiation: association with susceptibility and age at presentation with prostate cancer. Lancet 2001;358:641–42.[CrossRef][Web of Science][Medline]
11 Freedman DM, Dosemeci M, McGlynn K. Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case-control study. Occup Environ Med 2002;59:257–62.
12 Moon SJ, Fryer AA, Strange RC. Ultraviolet radiation: Effects on risks of prostate cancer and other internal cancers. Mutat Res 2005;571:207–19.[Medline]
13 Hughes AM, Armstrong BK, Vajdic CM et al. Sun exposure may protect against non-Hodgkin lymphoma: a case-control study. Int J Cancer 2004;112:865–71.[CrossRef][Web of Science][Medline]
14 Smedby KE, Hjalgrim H, Melbye M et al. Ultraviolet radiation exposure and risk of malignant lymphomas. J Natl Cancer Inst 2005;97:199–209.
15 Berwick M, Armstrong BK, Ben Porat L et al. Sun exposure and mortality from melanoma. J Natl Cancer Inst 2005;97:195–99.
16 Robsahm TE, Tretli S, Dahlback A, Moan J. Vitamin D3 from sunlight may improve the prognosis of breast-, colon- and prostate cancer. Cancer Causes Control 2004;15:149–58.[CrossRef][Web of Science][Medline]
17 Porojnicu AC, Robsahm TE, Ree AH, Moan J. Season of diagnosis is a prognostic factor in Hodgkin's lymphoma: a possible role of sun-induced vitamin D. Br J Cancer 2005;93:571–74.[CrossRef][Web of Science][Medline]
18 Boniol M, Armstrong BK, Dore JF. Variation in incidence and fatality of melanoma by season of diagnosis in New South Wales, Australia. Cancer Epidemiol Biomarkers Prev (in press).
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