Transcript A multifactor ecologic analysis of the geographic

Association of solar ultraviolet B with reduced mortality rates of some types of cancer: multifactorial ecologic study
William B. Grant, Ph.D., Sunlight, Nutrition and Health Research Center (SUNARC)
2107 Van Ness Avenue, Suite 403B, San Francisco, CA 94109-2529, [email protected], www.sunarc.org
Cedric F. Garland, Dr. P.H., Professor, Dept. of Family and Preventive Medicine, UC, San Diego, [email protected]
Objective. The objective of this study is to explain the
geographic variations in cancer mortality rates in the U.S.
Materials and Methods. Ecologic analyses of variations for a
number of cancers for the periods 1950-69 and 1970-94 in
the U.S. were performed using age-adjusted mortality rate
data in association with data on alcohol consumption,
Hispanic heritage, lung cancer mortality rates (as an index of
cigarette smoking), poverty, degree of urbanization, and
ultraviolet B (UVB) irradiance. The square root of the
mortality rate was used in the analysis.
The solar ultraviolet B (UVB) data used for this study were
obtained from the Total Ozone Mapping Spectrometer
(TOMS) data for July 1992 and digitized by state.
Photosynthesis from solar UVB is the largest source of
vitamin D. UVB is highest in the southwest and lowest in the
northeast. This distribution is primarily due to differences in
surface elevation (higher west of the Rocky Mountains) and
column ozone (lower west of the Rockies) and other factors.
The pronounced inverse correlation between UVB and
mortality rates for colon cancer was the first indication that
vitamin D reduces the risk of cancer [Garland and Garland,
1980]. While these UVB data are convenient to use, and
agree fairly well with ground-based data from the USDA UV-B
Monitoring and Research Program , vitamin D production
during other months is also important. In some regions of the
northeastern US, there is insufficient UVB to photosynthesize
vitamin D during 4-5 months of the year,
Mechanisms whereby vitamin D reduces
risk of cancer include differentiation, apoptosis;
reduced cell proliferation, metastasis, and angiogenesis;
Attenuation of growth signaling; increased calcium flux (for
the colon and breast); reduced breast density [Berube et al.,
2004]. Peripheral tissues convert 25(OH)D to 1,25(OH)2D
and vitamin D receptors mediate the actions of 1,25(OH)2D.
Summary of Findings of This Study
Factors ranked in order of standardized regression
(beta) coefficients; I (inverse)
Digestive Tract Cancers (males)
Esophageal: UVB (I), smoking, alcohol, poverty (I)
Gastric: UVB (I), Hispanic ancestry
Colon: UVB (I), smoking, urban, poverty (I)
Rectal: UVB (I), poverty (I), Hispanic ancestry,
smoking, alcohol
Breast and Reproductive System Cancers
Breast: UVB (I), urban, alcohol
Cervical: smoking, UVB (I), urban (I)
Endometrial: UVB (I), poverty (I)
Ovarian: UVB (I), poverty (I), alcohol
Urogenital Cancers (males)
Bladder: poverty (I), smoking, UVB (I)
Prostate: latitude, urban (I), UVB, poverty (I), alcohol
Renal: UVB (I), smoking
Other Cancers (males)
Gallbladder: UVB (I), Hispanic, urban
Laryngeal: smoking, UVB (I), urban
Pancreatic: smoking, UVB (I)
Hodgkin’s lymphoma: UVB (I), poverty, urban
Non Hodgkin’s lymphoma: UVB (I)
Skin Cancers (males)
Melanoma: latitude (a proxy for UVA)
Other skin cancer: latitude (I), alcohol, poverty
Gallbladder and gastric cancer morality rates show elevated risk associated with Hispanic heritage. The association of UVB
with prostate cancer is complex and will require further research; both low and high vitamin D appear associated with risk..
Key References
Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood
of colon cancer? Int J Epidemiol 1980;9:227-231.
Garland C, Shekelle RB, Barrett-Connor E, et al.. Dietary vitamin D and
calcium and risk of colorectal cancer: a 19-year prospective study in men.
Lancet. 1985;1:307-9.
Gorham ED, Garland CF, Garland FC. Acid haze air pollution and breast
and colon cancer mortality in 20 Canadian cities. Can J Public Health.
1989;80:96-100.
Hanchette CL, Schwartz GG. Geographic patterns of prostate cancer
mortality. Evidence for a protective effect of ultraviolet radiation. Cancer.
1992;70:2861-2869.
Lefkowitz ES, Garland CF. Sunlight, vitamin D, and ovarian cancer
mortality rates in U.S. women. Int J Epidemiol. 1994; 23: 1133-6.
Cross HS, Peterlik M, Reddy GS, Schuster I. Vitamin D metabolism in
human colon adenocarcinoma-derived Caco-2 cells: expression of 25hydroxyvitamin D3-1alpha-hydroxylase activity and regulation of sidechain metabolism. J Steroid Biochem Mol Biol. 1997;62:21-28.
Grant WB. An estimate of premature cancer mortality in the United
States due to inadequate doses of solar ultraviolet-B radiation. Cancer
2002;94:1867-1875.
Grant WB. An ecologic study of dietary and solar ultraviolet-B links to
breast carcinoma mortality rates. Cancer. 2002;94:272-281.
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;51:257-262.
Tuohimaa P, Tenkanen L, Ahonen M, et al. Both high and low levels of
blood vitamin D are associated with a higher prostate cancer risk: a
longitudinal, nested case-control study in the Nordic countries. Int J
Cancer. 2004;108:104-8.
Grant WB, Garland CF. A critical review of studies on vitamin D in
relation to colorectal cancer. Nutr Cancer, 2004;48:115-23.
Grant WB. Geographic variation of prostate cancer mortality rates in the
United States: Implications for prostate cancer risk related to vitamin D. Int
J Cancer. 2004;111:470-1.
Grant WB. Insufficient sunlight may kill 45,000 Americans each year from
internal cancer. J Cos Dermatol. 2004;3:176-8.
Smedby KE, Hjalgrim H, Melbye M, et al. Ultraviolet radiation exposure
and risk of malignant lymphomas. J Natl Cancer Inst. 2005;97:199-209.
Data Sources
Solar ultraviolet B and vitamin D
Solar UVB is the primary source of vitamin D.
Skin pigmentation has adapted through millennia to
prevailing solar UV irradiance. Hispanic and black
Americans have skin that protects against erythema but
reduces the production of vitamin D. With care, all can
obtain their vitamin D from UVB. Melanoma and basal
cell carcinoma (BCC) appear related mostly to UVA (315400 nm) overexposure, while actinic keratoses and
squamous cell carcinoma are mostly associated with
UVB overexposure. Use of sunscreen does not protect
against melanoma or BCC, and reduces the production of
vitamin D.
Vitamin D supplements should contain vitamin D3 and
should not contain vitamin A, which diminishes the
effectiveness of vitamin D by competition at the receptor
level. If taking vitamin D supplements, 1,000 I.U./day is
required for substantial reduction of incidence of
colorectal cancer. This dosage is safe according to the
National Academy of Sciences [NAS-Institute of
Medicine, Dietary reference intakes for calcium,
phosphorus, magnesium, vitamin D, and fluoride.
Washington DC: National Academy Press, 1997].
Other diseases related to vitamin D
There is evidence that vitamin D sufficiency is associated
with reduced incidence of bone and muscle diseases,
multiple sclerosis (MS), type 1 diabetes mellitus (DM),
myocardial infarction, and end stage renal disease and
secondary hyperparathyroidism (HPT) [Grant and Holick,
submitted]. There is also observational or other evidence
that vitamin D sufficiency may be associated with
reduced severity of rheumatoid arthritis, tuberculosis,
and type 2 diabetes.
Devesa SS, Grauman DJ, Blot WJ, Pennello GA, Hoover RN, Fraumeni JF Jr. Atlas of Cancer Mortality in the United States, 1950-1994. NIH
Publication No. 99-4564, 1999. http://cancer.gov/atlasplus/new.html
July 1992 DNA-weighted UVB irradiance: http://toms.gsfc.nasa.gov/ery_uv/dna_exp.gif
Nephew TM, Williams GD, Yi H, Hoy AK, Stinson FS, Dufour MC. Surveillance Report #59: Apparent Per Capita Alcohol Consumption:
National, State, and Regional Trends, 1977-99. Washington, DC: NIAAA, 2002. http://www.niaaa.nih.gov/publications/pcyr7099.txt
Hispanic heritage: http://www.census.gov/population/censusdata/urpop0090.txt
Gibson C, Jung K. Historical Census Statistics on Population Totals By Race, 1790 to 1990, and By Hispanic Origin, 1970 to 1990, For The United
States, Regions, Divisions, and States. Population Division. U. S. Census Bureau. Washington, DC 20233. Working Paper Series No. 56. 2002.
Data Maps
Cancer mortality rates on left;
Risk factors below and on right