Brief Reports

Role of Ultraviolet B Irradiance and Vitamin D in

Prevention of Ovarian Cancer
Cedric F. Garland, DrPH, Sharif B. Mohr, MPH, Edward D. Gorham, PhD, William B. Grant, PhD,
Frank C. Garland, PhD

Background: There is a north–south gradient in age-adjusted mortality rates of ovarian cancer in the
United States, with the highest rates in the Northeast and the lowest in the South through
Southwest. This suggests that lower levels of solar irradiance might be associated with
higher risk of ovarian cancer. Laboratory findings also suggest that low levels of vitamin D
metabolites could play a role in the etiology of ovarian cancer.
Methods: The association of solar ultraviolet B (UVB) irradiance, stratospheric column ozone, and
fertility rates at ages 15 to 19 years with incidence rates of ovarian cancer in 175 countries
in 2002 were examined using multiple linear regression in 2006.
Results: Age-adjusted ovarian cancer incidence rates generally were highest in countries located at
higher latitudes (R2⫽0.45, pⱕ0.01). According to multivariate analysis, UVB irradiance
(pⱕ0.002) and fertility rates at ages 15 to 19 (p⫽0.01) were inversely associated with
incidence rates, while stratospheric ozone (pⱕ0.0008), which reduces transmission of UVB,
was positively associated with incidence (R2⫽0.49, p⬍0.0001).
Conclusions: Solar UVB irradiance was inversely associated with incidence rates of ovarian cancer in
this study, adding new evidence to the theory that vitamin D might play a role in the
prevention of ovarian cancer. Cohort studies are needed to confirm this possible
association.
(Am J Prev Med 2006;31(6):512–514) © 2006 American Journal of Preventive Medicine

Introduction associated with lower regional sunlight, although two

reported no association in Norway10 and Japan.11 A

T
here are approximately 20,200 new cases and
15,300 deaths from cancer of the ovary each
year in the United States,1 but little is known
about its etiology. Mortality rates from ovarian cancer
are lowest in areas of the United States with high solar
irradiance2,3 and solar ultraviolet B (UVB),4 similar to
the pattern of lower rates in these areas of colon5 and
breast cancer in Canada,6 the United States,7 and the
former Soviet Union.8
Greater exposure to solar UVB in areas with high
solar irradiance results in greater cutaneous photosyn-
thesis of vitamin D in populations in these areas,
resulting in higher levels of anticarcinogenic vitamin D
metabolites.5
Of six studies of sunlight or UVB and ovarian can-
cer,2– 4,9 –11 four2– 4,9 reported higher mortality rates
From the Department of Family and Preventive Medicine, University
of California-San Diego (C. Garland, Gorham, F. Garland), La Jolla,
California; Behavioral Sciences and Epidemiology Program, Naval
Health Research Center (Mohr, Gorham, F. Garland), San Diego,
California; and Sunlight, Nutrition and Health Research Center
(Grant), San Francisco, California
Address correspondence and reprint requests to: Cedric F. Gar-
land, Department of Family and Preventive Medicine, University of
California San Diego, 9500 Gilman Drive, La Jolla CA 92093-0631.
E-mail: garlandc@nhrc.navy.mil.
case– control study reported that low oral vitamin D
intake was associated with twice the risk of ovarian
cancer.12 The present study characterizes differences in
ovarian cancer incidence rates in 175 countries accord-
ing to latitude, solar UVB irradiance, stratospheric
ozone, and fertility rates.
Methods
Data Sources
Age-adjusted incidence rates of ovarian cancer were obtained
for 175 countries using the International Agency for Research
on Cancer (IARC) GLOBOCAN database.13 GLOBOCAN
uses national cancer registries and vital events registers to
estimate annual age-adjusted incidence rates per 100,000
population in 175 countries. The latest year for which com-
plete data were available was 2002.
A file was created that contained information for each
country on solar UVB irradiance at the top of the atmosphere
at the vernal equinox, latitude, and total column ozone.
Because women in near-equatorial countries tended to have
more children at younger ages,14 fertility rates per 1000
women at ages 15 to 19 years14 were also obtained. Latitude
was determined for each country by using population cen-
troids provided by the Center for International Earth Sci-

512 Am J Prev Med 2006;31(6) 0749-3797/06/$–see front matter

© 2006 American Journal of Preventive Medicine • Published by Elsevier Inc. doi:10.1016/j.amepre.2006.08.018
ences Network of Columbia University. Stratospheric column
ozone was obtained from the National Aeronautics and Space
Administration’s satellite instrument packages.15
Amount of solar UVB irradiance at the top of the atmosphere,
by latitude, at the vernal equinox, was calculated with an
algorithm provided by Columbia University,16 which was derived
using the formula (A’ ⫽ A ⴱ cos x) where x is the latitude of the
country in degrees from the equator. A’ was defined as solar
radiation for the country’s latitude on the date of the winter
solstice, in watts/m2, and A was defined as solar radiation at the
equator.1 Because UVB is 0.4% of total solar irradiance, total
solar irradiance at the top of the atmosphere was multiplied by
0.004 in order to estimate the UVB irradiance.
Statistical Analysis
Age-adjusted incidence rates for each country were plotted by
latitude, and the best fit to the data points was obtained using
a polynomial trend line. Multiple linear regression was used
to assess the relationship between age-adjusted incidence
rates of ovarian cancer and solar UVB irradiance at the top of
the atmosphere in Watts/m2, stratospheric ozone in Dobson
units, and fertility rates at ages 15 to 19 years. Solar UVB
irradiance was estimated for the vernal equinox (March 21 in
the northern hemisphere and September 22 in the south-
ern). Stratospheric ozone was measured for the winter sol-
stice in each hemisphere. All analyses were performed in 2006
using JMP, version 5.1.2 (SAS Institute, Cary NC, 2005).
Results
Ovarian cancer incidence was in general highest at the
highest latitudes in both hemispheres (R2⫽0.45,
p⬍0.01) (Figure 1). After including UVB irradiance,
stratospheric ozone, and fertility rates at ages 15 to 19
in a regression model, UVB irradiance (p⬍0.01) and
fertility rates at ages 15 to 19 (p⫽0.002) were inversely
associated with incidence rates, while stratospheric
ozone (p⫽0.0008) was positively associated with inci-
dence rates (R2⫽0.49, p⬍0.0001) (Table 1).
Discussion and Conclusion
Only modest progress has been made to date in under-
standing the etiology of ovarian cancer. The main associ-
ations that have been reported are a positive association
with nulliparity,17 and higher number of ovarian cycles,18
and a negative association with oral contraceptive use.19
One observational study of the effect of vitamin D on
ovarian cancer risk was found in the literature search.12 It
reported an odds ratio of 0.43 (p⬍0.01) in women who
consumed more than 360 IU per day of vitamin D
compared to women who consumed less than 214 IU per
day. Migration studies would be useful in assessing the
relationship between age at trans-latitude migration and
risk of ovarian cancer, but such studies were beyond the
scope of this report.
The association of solar UVB irradiance and atmo-
spheric factors with risk of ovarian cancer (R2⫽0.49,
December 2006
Figure 1. Ovarian cancer age-adjusted incidence rates, by
latitude, 2002. Source: Data from GLOBOCAN. AUL, Austra-
lia; BHU, Bhutan; BOT, Botswana; BRU, Brunei; BUL, Bul-
garia; CAM, Cameroon; CAR, Central African Republic; CHL,
Chile; COL, Colombia; COM, Comoros; CRO, Croatia; DR,
Dominican Republic; EGY, Egypt; ELS, El Salvador; FIJ, Fiji;
FIN, Finland; GAM, Gambia; GTA, Guatemala; ICE, Iceland;
IDA, Indonesia; IRQ, Iraq; ISR, Israel; KUW, Kuwait; LES,
Lesotho; LIT, Lithuania; MLW, Malawi; MLY, Malaysia; MOL,
Moldova; MON, Mongolia; NAM, Namibia; NOR, Norway;
PAK, Pakistan; PAR, Paraguay; PER, Peru; PHI, Philippines;
PNG, Papua New Guinea; RUS, Russia; SA, South Africa;
SKO, South Korea; SLK, Slovakia; SLN, Sierra Leone; SLV,
Slovenia; SRL, Sri Lanka; SWE, Sweden; SWI, Switzerland;
TAJ, Tajikistan; TAN, Tanzania; TKN, Turkmenistan; TUN,
Tunisia; TUR, Turkey; UK, United Kingdom; USA, United
States; UZB, Uzbekistan; VAN, Vanuatu.
p⬍0.0001) is similar in strength and direction to that of
colon cancer (R2⫽0.61, p⬍0.01),20 suggesting that vita-
min D may play a role in ovarian cancer risk that could
be similar in magnitude to its reported association with
colon cancer. Fertility was inversely associated with
incidence of ovarian cancer, a finding that has been
observed in other studies.17 The independent associa-
tion of UVB with incidence of ovarian cancer does not
rule out the possibility of an association with dietary
factors, especially intake of red meat.21,22
Laboratory studies have found that the ovary contains
1,25(OH)2D receptors,23 and expresses vitamin D-1-al-
phahydroxylase (CYP27B1), an enzyme that metabolizes
serum 25(OH)D, the main circulating vitamin D metab-
olite, to 1,25(OH)2D, the most active vitamin D metabo-
lite.23 Two studies found that 1,25(OH)2D acts as a potent
anticarcinogen in the ovary.24,25 Because tissue levels of
1,25(OH)2D depend on serum 25(OH)D levels,26 which
in turn depend on sunlight or vitamin D intake,27,28 this
helps to explain a possible association between vitamin D
deficiency and risk of ovarian cancer.
There are many confounding variables besides sun
exposure associated with where a person lives and her risk
of ovarian cancer, such as lactation, hysterectomy, tubal
ligation, oral contraception, ethnicity, socioeconomic
Am J Prev Med 2006;31(6) 513
Table 1. Solar ultraviolet B irradiance and other covariates in association with ovarian cancer incidence rates, 175 countries,
2000a
Variable Coefficient Standard error
Solar UVB irradiance b
⫺0.3877 0.1236
Stratospheric ozonec 0.0271 0.0079
Fertility rate, ages 15–19 yearsd ⫺0.0103 0.0040
a
R 2⫽0.49, p⬍0.0001.
b
Watts/m2 at vernal equinox.
c
Ozone in Dobson units. (Source: NASA TOMS Satellite package.15)
d
Source: United Nations.14
*p⬍0.05;
**p⬍0.01;
***p⬍0.001.
class, and genetic factors. In addition, countries at the
highest latitudes that experience the highest incidence of
ovarian cancer are mostly developed countries, which
differ greatly from developing countries in terms of
reproductive factors, oral contraceptive use, and dietary
patterns. Therefore, the results of this study should be
considered as hypothesis generating and not definitive.
The evidence from this study adds to other studies2–
4,9,12,24,25 that suggest that vitamin D status may be
inversely associated with risk of ovarian cancer. More
observational studies, especially of large cohorts, are
needed to investigate this possible association.
This research was supported by a congressional allocation to the
Hollings Cancer Center of the Medical University of South
Carolina, Charleston SC and the Penn State University Cancer
Institute of the Hershey Medical Center, Hershey PA, through
the Department of the Navy, Bureau of Medicine and Surgery
(under Work Unit 60126). The views expressed in this report are
those of the authors and do not represent an official position of
the Department of the Navy, Department of Defense, or the U.S.
government.
WBG has provided expert testimony on UVB vitamin D for
Fabutan Corp, Canada, and has received fees for speaking on
the benefits of UVB exposure and vitamin D to reduce the
risk of cancer.
No other financial conflicts of interest were reported by the
authors of this paper.
References
1. American Cancer Society. Cancer facts and figures, 2006. Atlanta GA:
American Cancer Society, 2006.
2. Lefkowitz ES, Garland CF. Sunlight, vitamin D, and ovarian cancer
mortality rates in U.S. women. Int J Epidemiol 1994;23:1133– 6.
3. Freedman D, 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.
4. Grant WB. An estimate of premature cancer mortality in the U.S. due to
inadequate doses of solar ultraviolet-B radiation. Cancer 2002;94:1867–75.
5. Garland C, Garland F. Do sunlight and vitamin D reduce the likelihood of
colon cancer? Int J Epidemiol 1980;9:227–31.
6. Gorham E, Garland C, Garland F. Acid haze air pollution and breast and
colon cancer in 20 Canadian cities. Can J Public Health 1989;80:96 –100.
7. Garland F, Garland C, Gorham E, Young J Jr. Geographic variation in
breast cancer mortality in the United States: a hypothesis involving expo-
sure to solar radiation. Prev Med 1990;19:614 –22.
514 American Journal of Preventive Medicine, Volume 31, Number 6
Normalized regression
coefficient t p
⫺0.2241 ⫺3.14 0.002**
0.2222 3.40 0.0008***
⫺0.0669 ⫺2.57 0.01*
8. Gorham ED, Garland FC, Garland CF. Sunlight and breast cancer inci-
dence in the USSR. Int J Epidemiol 1990;19:820 – 4.
9. Grant WB. Ecologic studies of solar UV-B radiation and cancer mortality
rates. Recent Results Cancer Res 2003;164:371–7.
10. Robsahm TE, Tretli S, Dahlback A, Moan J. Vitamin D3 from sunlight may
improve the prognosis of breast-, colon- and prostate cancer (Norway).
Cancer Causes Control 2004;15:149 –58.
11. Mizoue T. Ecological studies of solar radiation and cancer mortality in
Japan. Health Phys 2004;87:532– 8.
12. Salazar-Martinez E, Lazcano-Ponce EC, Gonzalez Lira-Lira G, Escudero-De los
Rios P, Hernandez-Avila M. Nutritional determinants of epithelial ovarian
cancer risk: a case-control study in Mexico. Oncology 2002;63:151–7.
13. Ferlay J, Bray F, Pisani P, Parkin D. GLOBOCAN 2002: cancer incidence,
mortality and prevalence worldwide. IARC CancerBase No. 5, version 2.0.
Lyon: IARC Press, 2004.
14. United Nations Population Division. World population prospects: the 2004
revision population database. Available at: http://esa.un.org/unpp/index.
asp?panel⫽2.
15. U.S. National Aeronautics and Space Administration. Total Ozone Map-
ping Spectrometer (TOMS) images. Available at: http://jwocky.gsfc.
nasa.gov/eptoms/ep.html.
16. Columbia University. The Earth’s radiation budget, part I. Available at:
www.ldeo.columbia.edu/edu/dees/ees/climate/labs/radiation1/.
17. Edmondson RJ, Monaghan JM. The epidemiology of ovarian cancer. Int J
Gynecol Cancer 2001;11:423–9.
18. Holschneider CH, Berek JS. Ovarian cancer: epidemiology, biology, and
prognostic factors. Semin Surg Oncol 2000;19:3–10.
19. Pike MC, Spicer DV. Hormonal contraception and chemoprevention of
female cancers. Endocr Relat Cancer 2000;7:73– 83.
20. Gorham E, Garland C, Garland F, et al. Vitamin D and prevention of colon
cancer. J Steroid Biochem Mol Biol 2006. In press.
21. Bosetti C, Negri E, Franceschi S, Pelucchi C, Talamini R, Montella M, et al.
Diet and ovarian cancer risk: a case-control study in Italy. Int J Cancer
2001;93:911–5.
22. Tavani A, La Vecchia C, Gallus S, et al. Red meat intake and cancer risk: a
study in Italy. Int J Cancer 2000;86:425– 8.
23. Friedrich M, Rafi L, Mitschele T, Tilgen W, Schmidt W, Reichrath J.
Analysis of the vitamin D system in cervical carcinomas, breast cancer and
ovarian cancer. Recent Results Cancer Res 2003;164:239 – 46.
24. Li P, Li C, Zhao X, Zhang X, Nicosia SV, Bai W. p27(Kip1) stabilization and
G arrest by 1,25-dihydroxyvitamin D in ovarian cancer cells mediated
through down-regulation of cyclin E/cyclin-dependent kinase 2 and Skp1-
Cullin-F-box protein/Skp2 ubiquitin ligase. J Biol Chem 2004;279:25260 –7.
25. Jiang F, Bao J, Li P, Nicosia SV, Bai W. Induction of ovarian cancer cell
apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of
telomerase. J Biol Chem 2004;279:53213–21.
26. Bouillon RA, Auwerx JH, Lissens WD, Pelemans WK. Vitamin D status in
the elderly: seasonal substrate deficiency causes 1,25-dihydroxycholecalcif-
erol deficiency. Am J Clin Nutr 1987;45:755– 63.
27. Holick M. Photosynthesis of previtamin D3 in human skin and the
physiological consequences. Science 1980;210:203–5.
28. Guillemant J, Le HT, Maria A, Allemandou A, Peres G, Guillemant S.
Wintertime vitamin D deficiency in male adolescents: effect on parathyroid
function and response to vitamin D3 supplements. Osteoporos Int
2001;12:875–9.
www.ajpm-online.net