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MAPPING VITAMIN D DEFICIENCY, BREAST CANCER, AND COLORECTAL CANCER

Authors:
  • Sunlight, Nutrition and Health Research Center

Abstract and Figures

Breast and colorectal cancer incidence rates are highest in countries distant from the equator and lowest in near-equatorial countries. It is known that adequate levels of vitamin D, which require sunlight for synthesis in the skin, tend to be associated with lower age-adjusted incidence rates of these cancers. Residents of near-equatorial areas synthesize far more vitamin D than those living at high latitudes. To describe the associations of these cancers with ultraviolet B (UVB) irradiance, we obtained sunlight measurements from the National Aeronautics and Space Administration (NASA), and age-adjusted breast and colorectal cancer incidence rates for 175 countries from the International Agency for Research on Cancer Global Cancer Database (GLOBOCAN). We created Geographic Information Systems displays of the association between sunlight levels and disease rates using three-dimensional analysis. Countries that received the lowest solar irradiance had rates of breast and colorectal cancer that were several times greater than those of countries with the highest solar irradiance. Countries with intermediate irradiance had intermediate rates of colorectal and breast cancer incidence. Dietary differences might explain some but not all of this association.
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!
M
APPING!VITAMIN!D!DEFICIENCY,!!
BREAST!CANCER,!AND!COLORECTAL!CANCER!
SHARIF!B.!MOHR
1
!
CEDRIC!F.!GARLAND
1,2!
EDWARD!D.!GORHAM
1,2!
WILLIAM B. GRANT
3
ROBYN M. HIGHFILL
1
!
FRANK!C.!GARLAND
1,2
(1) Naval Health Research Center, San Diego CA 92186
(2) Department of Family and Preventive Medicine, School of Medicine, University of
California San Diego, La Jolla, CA
(3) Sunlight, Nutrition, and Health Research Center, San Francisco, CA
ABSTRACT
Breast and colorectal cancer incidence rates are highest in countries distant from the equator and
lowest in near-equatorial countries. It is known that adequate levels of vitamin D, which require
sunlight for synthesis in the skin, tend to be associated with lower age-adjusted incidence rates of
these cancers. Residents of near-equatorial areas synthesize far more vitamin D than those living
at high latitudes. To describe the associations of these cancers with ultraviolet B (UVB)
irradiance, we obtained sunlight measurements from the National Aeronautics and Space
Administration (NASA), and age-adjusted breast and colorectal cancer incidence rates for 175
countries from the International Agency for Research on Cancer Global Cancer Database
(GLOBOCAN). We created Geographic Information Systems displays of the association
between sunlight levels and disease rates using three-dimensional analysis. Countries that
received the lowest solar irradiance had rates of breast and colorectal cancer that were several
times greater than those of countries with the highest solar irradiance. Countries with
intermediate irradiance had intermediate rates of colorectal and breast cancer incidence. Dietary
differences might explain some but not all of this association.
INTRODUCTION
Age-adjusted breast and colorectal cancer incidence rates exhibited a strong latitudinal
gradient, with highest incidence rates in countries distant from the equator. By contrast,
countries closer to the equator experienced much lower incidence rates. This may
implicate inadequate levels of ultraviolet B (UVB), which is needed for photosynthesis of
vitamin D and its metabolites. Low levels of serum 25-hydroxyvitamin D (25[OH]D) are
associated with increased risk of colorectal cancer (1-4). Other factors related to sunlight
and ultraviolet B exposure, such as amount of anthropogenic sulfate-carbon pollution in
the troposphere (5), urbanization, population density, and proportion of the population
engaged outdoors in agriculture may also play an important role. Previous
epidemiological studies have found a statistically significant beneficial effect of vitamin
D or its markers on colorectal and breast cancer risk (1-20). Further evidence is provided
here for the protective effect of solar irradiance and photosynthesized vitamin D for these
cancers.
Residents of areas distant from the equator photosynthesize less vitamin D than those
living at lower latitudes (21). Equatorial countries receive much more UVB than
countries more distant from the equator, which accounts for the latitudinal difference.
Areas nearer the equator also tend to have a higher proportion of their population
engaged in outdoor occupations where individuals would have high occupational
exposure to UVB. This is in contrast to countries at higher absolute latitudes, where most
work tends to be performed indoors.
METHODS
Geographic Information Systems (GIS) displays were created of colorectal and breast
cancer incidence rates, total solar irradiance during the vernal equinox, and ground level
UVB flux, the latter based on a map created by Lubin et al (22). Multiple linear
regression was performed using JMP 5.1.2 (Cary NC: SAS Institute) to examine the
association of age-adjusted incidence rates of colorectal and breast cancer with the above
factors and with total percentage cloud cover, anthropogenic sulfate aerosol optical depth,
stratospheric ozone thickness, population density, urbanization, and proportion of the
population engaged in agriculture. The International Agency for Research on Cancer
(IARC) GLOBOCAN database (23) provided estimated age-adjusted incidence rates for
colorectal and breast cancer for 175 countries. The rates were adjusted by the direct
method to the world standard population. Columbia University provided total solar
radiation at solar noon at the top of the atmosphere on the date of the vernal equinox in
each hemisphere (24). Column sulfate aerosol optical depth at 550 nm and total
proportion of cloud cover data were obtained through the National Aeronautics and Space
Administration (NASA) from various United States and European satellite packages (25,
26). Countries that were not industrialized were categorized for this study as not having
anthropogenic sulfate aerosols. The proportion of the labor force engaged in agriculture
in each country was obtained from Federal Government sources (27). Data on
urbanization and population density were obtained from the United Nations statistics
division (28-30). Population density was defined as the number of individuals per km2.
Adjustment for population density was performed using the following heuristic formula:
adjusted incidence rate = unadjusted incidence rate * (e-1*[(ln population density)/10]).
RESULTS
Countries distant from the equator had the lowest total solar irradiance at the top of the
atmosphere (Figure 1) and UVB (Figure 2).
Figure 1
Total solar irradiance at the vernal equinox at the top of the atmosphere, solar noon,
Watts/meter
2
Solar irradiance watts/m
2
458.60 - 687.90
687.90 - 917.20
917.20 - 1228.00
1228.00 - 1375.81
Source: Columbia University (19)
Figure 2
Estimated equinoctial ultraviolet B flux (280-315 nm) at ground level, solar noon,
Watts/meter
2
. The measurements were integrated over the UVB range.
Source of data used for creation of this map: Dan Lubin and associates, California Space
Institute, Scripps Institution of Oceanography, University of California San Diego (22)
The maps of colorectal and breast cancer by country (Figures 3-5) revealed the highest
incidence rates of colorectal and breast cancer in areas of low total solar irradiance and
UVB.
Figure 3
Age-adjusted colorectal cancer incidence rates, by country, males, 2000.
Incidence pe r 100,000
No data
0.1 - 11.0
11.0 - 25.0
25.0 - 39.0
39.0 - 59.1
Source: GLOBOCAN (18)
Figure 4
Age-adjusted colorectal cancer incidence rates, by country, females, 2000
Incide nce pe r 100,000
No data
0.1 - 12.5
12.5 - 16.0
16.0 - 30.0
30.0 - 42.1
Source: GLOBOCAN (18)
Figure 5
Age-adjusted breast cancer incidence rates, by country, females, 2000
Incide nce pe r 100,000
No data
0.1 - 28.0
28.0 - 35.5
35.5 - 75.8
75.8 - 101.1
Source: GLOBOCAN (18)
Male colorectal cancer was highly correlated with latitude R
2
= 0.47 (Figure 6), a
correlation that persisted and was strengthened by adjustment for population density
(Figure 7). Abbreviations for countries shown in figures are provided in Appendix Table
1.
Figure 6
Colorectal cancer incidence rates, by latitude, males, 2000
0
10
20
30
40
50
60
Incidence rate
ANG
ARG
AUL
AUS
BAN
BAR
BGM
BHM
BOL
BOS
BRZ
BUL
CAR
CBA
CHI
CHL
COM
CYP
CZR
DEN
DRC
EGY
ERI
EST
GAB
GEO
GER
GRE
GUA
ICE
IDA
IND
ISR
ITA
JAP
JOR
KAZ
LAT
MAL
MEX
MLY
MON
MOZ
NOR
NZL
PAN
PAR
PHI
PR
ROM
RUS
SA
SER
SIN
SLK
SPA
SUR
SWA
TKN
TUN
UK
URU
USA
YEM
ZIM
-50 -40 -30 -20 -10 0 10 20 30 40 50 60 70
Latitude
Source: GLOBOCAN (18)
Figure 7
Colorectal cancer incidence rates, by latitude adjusted for population density, males, 2000
0
5
10
15
20
25
30
35
40
45
Incidence rate
ANG
ARG
AUL
BAN
BAR
BGM
BHM
BOL
BOS
BRZ
CAN
CAR
CBA
CHI
CHL
CRA
CYP
CZR
DEN
DRC
EGY
ERI
FIN
GAB
GEO
GER
GRE
ICE
IDA
IND
IRE
ISR
JAP
JOR
LAT
MAL
MEX
MLY
MON
MOZ
NOR
NZL
PAR
PHI
PR
ROM
RUS
SA
SER
SIN
SLK
SPA
SUR
SWA
TKN
TUN
UK
URU
USA
ZIM
-50 -40 -30 -20 -10 0 10 20 30 40 50 60 70
Latitude
Source: GLOBOCAN (18)
Female colorectal cancer incidence rates and latitude had an unadjusted R
2
= 0.45 (Figure
8) and a population-density adjusted R
2
= 0.49 (Figure 9).
Figure 8
Colorectal cancer incidence rates, by latitude, females, 2000
0
5
10
15
20
25
30
35
40
45
Incidence
ALG
ARG
AUL
BAH
BAN
BAR
BFS
BHM
BOS
BOT
BRU
BRZ
CAM
CAN
CDI
CHI
COM
CYP
DEN
EST
FIN
FRA
GRE
GUY
HUN
ICE
IDA
ISR
JAM
JAP
KAZ
KYR
LAO
LAT
LEB
MAC
MAL
MLY
MON
MOZ
NET
NOR
NZL
OMA
PAR
PLY
PND
PNG
PR
QAT
ROM
SA
SIN
SOL
SWA
SYR
TAJ
THA
TRI
TUN
TUR
UAE
UGA
UK
URU
USA
VEN
VIE
ZIM
-50 -40 -30 -20 -10 0 10 20 30 40 50 60 70
Latitude
Source: GLOBOCAN (18)
Figure 9
Colorectal cancer incidence rates, by latitude adjusted for population density, females,
2000
0
5
10
15
20
25
30
Incidence rate
ANG
AUL
BAN
BAR
BFS
BOS
BRZ
CAN
CAV
CDI
CHI
CHL
COL
CZR
DEN
DR
DRC
ECU
FIN
FRA
GAB
GEO
GRE
GUA
GUI
GUY
HON
HUN
ICE
IRE
ISR
JAP
KAZ
LAT
LIT
MAL
MAU
MEX
MON
MOR
NAM
NEP
NOR
NZL
PAR
PER
PHI
POR
QAT
ROM
SA
SAU
SER
SIN
SLK
SUR
SWA
SWE
TAJ
TAN
UAE
UK
URU
USA
ZIM
-50 -40 -30 -20 -10 0 10 20 30 40 50 60 70
Latitude
Source: GLOBOCAN (18)
Female breast cancer incidence rates were also highly associated with latitude and
latitude adjusted for population density, R
2
= 0.43 (Figure 10), and 0.46 (Figure 11)
respectively.
Figure 10
Breast cancer incidence rates, by latitude, females, 2000
0
10
20
30
40
50
60
70
80
90
100
110
Incidence rate
ANG
ARG
AUL
AUS
AZR
BAN
BAR
BHM
BRZ
CAV
CHL
COL
CYP
CZR
DRC
EGY
EST
ETH
FRA
HAI
HUN
ICEISR
ITA
JAM
KYR
LAO
MON
MOZ
MRT
NAM
NOR
NZL
PER
PNG
POR
QAT
RUS
SA
SIN
SOL
SOM
SWA
SWI
SYR
UK
USA
UZB
VEN
-50 -40 -30 -20 -10 0 10 20 30 40 50 60 70
Latitude
Source: GLOBOCAN (18)
Figure 11
Breast cancer incidence rates, by latitude adjusted for population density, females, 2000
0
10
20
30
40
50
60
70
80
Incidence rate
ANG
ARG
AUL
AUS
AZR
BAN
BAR
BEL
BFS
BHM
BRZ
CAN
CAV
CHL
CYP
CZR
DRC
EGY
EST
ETH
FRA
GUA
HAI
HUN
ICE
IRQ
ISR
ITA
JAM
KAZ
KYR
LAO
MAL
MLW
MON
MOZ
MRT
NAM
NEP
NOR
NZL
PER
PNG
POR
QAT
ROM
RUS
RWA
SA
SEN
SIN
SOL
SUR
SWA
SWE
SWI
SYR
TAJ
TRI
UGA
UK
URU
USA
UZB
VEN
ZAM
ZIM
-50 -40 -30 -20 -10 0 10 20 30 40 50 60 70
Latitude
Source: GLOBOCAN (18)
A regression model for male colorectal cancer incidence accounted for 68% of the
variation in rates (R
2
= 0.68) (Table 1). Total solar irradiance at the top of the atmosphere
(p = 0.0004) and proportion of the population engaged in agriculture (p = 0.002), were
statistically significantly inversely associated with colorectal cancer incidence, while total
cloud cover (p = 0.002) and anthropogenic sulfate aerosol optical depth (p = 0.0003)
were positively associated. Stratospheric ozone thickness was not significantly related to
incidence rates of colorectal or breast cancer, and was therefore not included in further
regressions.
Table 1. Association of total solar irradiance and other variables with age-adjusted
incidence rates of colorectal cancer per 100,000 population, males, 175 countries,
2000
Regression Standard
Variable coefficient error
t p
Total solar irradiance, W/m
2*
-0.0181 0.005 -3.53 0.0004
Total cloud cover, pro- 19.9350 6.203 3.21 0.002
portion
Anthropogenic sulfate aerosol 19.0711 5.116 3.73 0.0003
optical depth
Proportion of population 0.0195 0.061 0.32 0.75
living in urban areas
Population density, 0.0016 0.001 1.16 0.25
individuals/km
2
Proportion of population -0.1668 0.053 -3.12 0.002
engaged in agriculture
R
2
for model = 0.68
p
for model < 0.0001
*At equinox.
Results were similar for females (Table 2) with the main difference being the larger
coefficient of variation (R
2
= 0.73). The proportion of the population living in urban
areas was associated with the colorectal cancer incidence rate in females but not males.
Table 2. Association of total solar irradiance and other variables with age-adjusted
incidence rates of colorectal cancer per 100,000 population, females, 175 countries,
2000
Regression Standard
Variable coefficient error
t p
Total solar irradiance, W/m
2*
-0.0096 0.003 -3.02 0.003
Total cloud cover, pro- 14.8314 3.856 3.85 0.0002
portion
Anthropogenic sulfate aerosol 9.6355 3.181 3.03 0.003
optical depth
Proportion of population 0.0792 0.038 2.08 0.04
living in urban areas
Population density, 0.0012 0.001 1.38 0.17
individuals/km
2
Proportion of population -0.0988 0.033 -2.97 0.004
engaged in agriculture
R
2
for model = 0.73
p
for model < 0.0001
*At equinox.
Total solar irradiance (p = 0.0003) and proportion of the population engaged in
agriculture (p = 0.05) were statistically significantly inversely associated with incidence
rates of female breast cancer (Table 3). Total cloud cover (p = 0.02) and the proportion of
the population living in urban areas (p = 0.05), were statistically significantly positively
associated with incidence rates.
Table 3. Association of total solar irradiance and other variables with
age-adjusted incidence rates of breast cancer per 100,000 population,
females, 175 countries, 2000
Regression Standard
Variable coefficient error
t p
Total solar irradiance, W/m
2*
-0.0327 0.009 -3.69 0.0003
Total cloud cover, pro- 26.0517 10.723 2.43 0.02
portion
Anthropogenic sulfate aerosol 13.2226 8.844 1.5 0.14
optical depth
Proportion of population 0.2067 0.106 1.95 0.05
living in urban areas
Population density, -0.0001 0.002 -0.04 0.97
individuals/km
2
Proportion of population -0.1818 0.092 -1.97 0.05
engaged in agriculture
R
2
for model =0.63
p
for model < 0.0001
*At equinox.
CONCLUSIONS
Countries with persistently high percentage of cloud cover had significantly higher
incidence rates of breast and colon cancer. This is the first report to our knowledge of an
adverse association between persistent cloud cover and incidence of any disease.
Consistent with the association with cloud cover, places that had the lowest solar
irradiance had incidence rates of breast and colorectal cancer that were several times
greater than those with the highest. Countries with intermediate irradiance had
intermediate incidence rates. Countries with high levels of anthropogenic sulfate aerosols
(acid haze) also had significantly higher incidence rates of breast and colon cancer than
those with lower levels, consistent with previous research (5). Such aerosols are the
cause of acid precipitation. Their geographic distribution is nearly identical to that of
acid rain (5, 20).
The aerosol optical depths reported by the MODIS package on the Terra satellite were
higher than expected. This suggests the possibility that attenuation of solar radiation may
have been greater than anticipated due to the presence of optically-absorbing particles,
such as elemental carbon (soot) in association with sulfate particles, and possibly
optically-absorbing sulfuric and sulfurous acid droplet aerosols. This is consistent with
recent reports of extensive, thick, and highly persistent atmospheric brown clouds in the
northern hemisphere. The brown clouds are due to the combustion of high sulfur content
bituminous (soft) coal in Asia and the U.S., mainly for electric power generation.
Sulfate-carbonaceous acid haze air pollution is almost exclusively due to burning of soft
coal, and it strongly attenuates UVB (5). However more research is needed to determine
the extent to which the brown cloud and other anthropogenic aerosols are contaminated
with particles that absorb UVB.
The lack of a statistically significant association of stratospheric ozone thickness with
incidence rates was apparently due to the relative uniformity of ozone thickness among
countries, particularly at the equinox. It may have a greater effect at other times of year,
when the distribution of stratospheric ozone could be less uniform. The graphs of
incidence rates were presented according to latitude, which is directly related to total
solar irradiance at the top of the atmosphere. This type of display allows comparison of
the associations with breast and colon cancer in the northern hemisphere compared to the
southern. Similar associations were observed when the incidence rates were plotted
according to total solar irradiance, but, as expected from the earth's approximately
spherical shape, the least-squares lines for the associations tended to be straight or mildly
curvilinear (not shown). The purpose of the maps presented here is to allow
comparisons among countries. The data on which the maps are based generally provided
more geographic resolution than was shown, namely overall estimates for entire
countries. Studies that can take advantage of regional differences in incidence rates
within countries should geocode the data provided in the original sources cited in the
references, rather than use these maps.
The regression models presented here used total solar irradiance at the top of the
atmosphere, and atmospheric characteristics that reduce transmission of UVB and tend to
vary considerably by location, namely cloud cover and column aerosol optical depth, as
the predictor variables. Total solar irradiance at the top of the atmosphere was used since
existing estimates of UVB irradiance derived from remote sensing platforms such as
TOMS and ERBE do not adequately account for the effect of clouds on UVB extinction
(Jay R. Herman, personal communication, 2005). If more information were available on
cloud-cover parameters, including the extinction by clouds at UVB wavelengths, it is
likely that the explanatory power of the regression models that were used could be
enhanced. The regression models did not include Rayleigh scatter, whose attenuation
varies as the inverse of the fourth power of the wavelength. As a result of this
wavelength dependence, extinction due to Rayleigh scatter, although probably relatively
minor, would be greater for UVB than for visible light. The models might have
accounted for slightly more of the variance in incidence rates if Rayleigh scatter had been
taken into account.
More research is clearly needed on absorption and reflection of UVB by clouds, on a
global basis. Above all, more numerous and evenly dispersed ground photometer stations
are needed to measure ultraviolet radiation (290-400 nm) in nanometer increments, and to
provide measurements that are difficult or impossible to accomplish by remote sensing,
such as UVB irradiance in cities, where the UVB absorptive effects of sulfate-
carbonaceous aerosol "dust domes" may be prominent. High-resolution remote sensing
and ground based spectrophotometer measurements are complementary, and expansion of
both types of sensing is needed to adequately understand and monitor the prominent
effects of ultraviolet radiation on human health.
Previous studies have reported associations between dietary factors and risk of colorectal
cancer incidence or mortality, such as an adverse association of intake of animal protein
as a proportion of total energy intake with mortality, and of regular intake of red meat
with incidence (31-32). These associations are thought to be due to intake of
carcinogenic polyamines (32). The present analysis did not include these dietary factors
in the regression models. However, it is likely that variation between countries in them
could account for variance that was not accounted for by total solar irradiance or UVB.
Differences in age at first pregnancy might explain some of the unexplained variance in
incidence rates of breast cancer. However it is unlikely that differences in age at first
pregnancy could account for the inverse association with solar irradiance, which is
stronger. Differences in sex hormone concentrations in women among countries are
generally minor, and could not account for these findings. All incidence rates were age-
adjusted to the same world standard (23), so differences in age distributions among the
countries could not explain any of the associations.
Since the ability of a country to detect and report cancer incidence may depend to a
degree on level of economic development, this possibility was tested by including per
capita health expenditure by country in further regression models. While this variable had
some explanatory power, total solar irradiance and the variables that reduced UVB
irradiance, such as total cloud cover and anthropogenic aerosol optical depth, had the
most powerful effects. These findings support previous research indicating that solar
irradiance, UVB, and photosynthesized vitamin D are associated with lower incidence of
cancers of the colon (1-4, 6-15) and breast (5, 14-20). Preventive measures should
include elimination of anthropogenic sulfate-carbonaceous (acid haze) aerosols that
interfere with photosynthesis of vitamin D. Elimination of these anthropogenic aerosols
would also reduce cloud cover, as cloud cover tends to be associated with sulfate aerosols
that provide condensation nuclei. Ten to fifteen minutes per day of exposure to sunlight
between 10:00 AM and 2:00 PM should be encouraged, without sunscreen, at all ages.
At least one square foot of skin should be exposed for adequate vitamin D
photosynthesis, preferably not the face. Such exposure would prevent nine or more cases
of potentially fatal internal cancers for each possible case of skin cancer that it might
cause.
Vitamin D is also available in oral form, but only in acceptable doses far lower than those
associated with 10-15 minutes of solar exposure. Individuals wishing to consume
vitamin D for reduction of risk of colon and breast cancer should consume at least 1,000
IU/day of vitamin D3 (33), but should not, according to present U.S. guidelines, exceed
2,000 IU/day (34). According to a consensus of observational studies conducted over a
period of 20 years, adequate exposure of the population to moderate amounts mid-day
sunlight or oral vitamin D
3
could reduce the incidence of colon cancer by at least 50%
(35).
The worldwide geographic distribution of breast cancer incidence rates (Figure 5) was
highly similar to the distribution of colorectal cancer incidence rates (Figures 3 and 4).
Rates tended to be lowest in regions of high solar radiation (Figures 1 and 2), and highest
in areas with low solar radiation. This effect is probably due to vitamin D status in
childhood and early adolescence. If initiated in early childhood, the preponderance of
epidemiological evidence suggests that moderate amounts mid-day sunlight or oral
vitamin D
3
could similarly reduce the incidence of breast cancer (5, 16, 18-20).
Delays in implementing simple and inexpensive preventive actions to improve vitamin D
status would be unwise, considering that annually there are 357,000 new cases and
106,000 deaths from breast and colorectal cancers in the U.S. (36) and 2.2 million new
cases and 940,000 deaths in the world (37), at least half of which could be prevented.
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APPENDIX
Table 1. Abbreviations for countries
AFG Afghanistan CRA Costa Rica
ALB Albania CRO Croatia
ALG Algeria CYP Cyprus
ANG Angola CZR Czech Republic
ARG Argentina DEN Denmark
ARM Armenia DJI Djibouti
AUL Australia DR Dominican Republic
AUS Austria DRC Congo
AZR Azerbaijan ECU Ecuador
BAH Bahrain EGY Egypt
BAN Bangladesh ELS El Salvador
BAR Barbados EQG Equatorial Guinea
BEL Belarus ERI Eritrea
BEN Benin EST Estonia
BFS Burkina Faso ETH Ethiopia
BGM Belgium FIJ Fiji
BHM Bahamas FIN Finland
BHU Bhutan FRA France
BLZ Belize GAB Gabon
BOL Bolivia GAM Gambia
BOS Bosnia Herzegovena GEO Georgia
BOT Botswana GER Germany
BRU Brunei GHA Ghana
BRZ Brazil GIB Guinea-Bissau
BUL Bulgaria GRE Greece
BUR Burundi GTA Guatemala
CAM Cameroon GUA Guam
CAN Canada GUI Guinea
CAR Central African Republic GUY Guyana
CAV Cape Verde HAI Haiti
CBA Cuba HON Honduras
CBD Cambodia HUN Hungary
CDI Cote d'Ivoire ICE Iceland
CGB Congo Brazzaville IDA Indonesia
CHD Chad IND India
CHI China IRE Ireland
CHL Chile IRN Iran, Islamic Republic of
COL Colombia IRQ Iraq
COM Comoros ISR Israel
ITA Italy OMA Oman
JAM Jamaica PAK Pakistan
JAP Japan PAN Panama
JOR Jordan PAR Paraguay
KAZ Kazakhstan PER Peru
KEN Kenya PHI Philippines
KUW Kuwait PLY Polynesia
KYR Kyrgyzstan PND Poland
LAO Laos PNG Papua New Guinea
LAT Latvia POR Portugal
LBY Libya PR Puerto Rico
LEB Lebanon QAT Qatar
LES Lesotho ROM Romania
LIB Liberia RUS Russian Federation
LIT Lithuania RWA Rwanda
LUX Luxembourg SA South African Republic
MAC Macedonia SAM Samoa
MAD Madagascar SAU Saudi Arabia
MAL Malta SEN Senegal
MAU Mauritania SER Serbia and Montenegro
MEL Melanesia SIN Singapore
MEX Mexico SKO Korea, Republic of
MIC Micronesia SLK Slovakia
MLI Mali SLN Sierra Leone
MLW Malawi SLV Slovenia
MLY Malaysia SOL Solomon Islands
MOL Moldava SOM Somalia
MON Mongolia SPA Spain
MOR Morocco SRL Sri Lanka
MOZ Mozambique SUD Sudan
MRT Mauritius SUR Suriname
MYA Myanmar SWA Swaziland
NAM Namibia SWE Sweden
NEP Nepal SWI Switzerland
NET Netherlands SYR Syrian Arab Republic
NGA Nigeria TAJ Tajikistan
NIC Nicaragua TAN Tanzania
NIG Niger THA Thailand
NKO Korea, Democratic Republic of TKN Turkmenistan
NOR Norway TOG Togo
NZL New Zealand TRI Trinidad and Tobago
TUN Tunisia
TUR Turkey
UAE United Arab Emirates
UGA Uganda
UK United Kingdom
UKR Ukraine
URU Uruguay
USA United States of America
UZB Uzbekistan
VAN Vanuatu
VEN Venezuela
VIE Viet Nam
YEM Yemen
ZAM Zambia
ZIM Zimbabwe
CORRESPONDING AUTHOR INFORMATION
Cedric F. Garland, Dr.P.H., F.A.C.E.
Professor
Department of Family and Preventive Medicine
University of California, San Diego
9500 Gilman Drive, Dept. 0631C
La Jolla CA 92093-0631, and
Naval Health Research Center
P.O. Box 85122
San Diego CA 92186-5122
Telephone (858) 534-0520/(619) 553-9016
E-mail: cgarland@ucsd.edu
Fax: (858) 534-3777
ACKNOWLEDGEMENTS
This research was supported by a Congressional allocation to the Hollings Cancer Center of the Medical
University of South Carolina, Charleston SC, through the Department of the Navy, Bureau of Medicine and
Surgery, under Work Unit No. 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. Approved for public release; distribution unlimited.
... There was an independent inverse association of UVB irradiance with incidence rates of multiple myeloma, while controlling for several other factors. The percentage of variation among countries explained for multiple myeloma was similar to cancers for which a role of vitamin D has been established in observational studies of individuals, including those of breast (R 2 = 0.55, p < 0.0001) [36], colon (R 2 = 0.68, p < 0.0001) [36], and ovary (R 2 = 0.60, p < 0.0001) [20]. However, studies of this type should be considered as hypothesis-generating, rather than definitive. ...
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Experimental and human epidemiologic data suggest a protective rolefor vitamin D in large bowel cancer. To investigate this association, weconducted a nested case-control study within a Finnish clinical trial cohort.Cases (n = 146) were participants diagnosed with primary adenocarcinoma ofthe large bowel. Controls were matched (2:1) to cases on age, date ofbaseline blood draw, and study clinic. Prediagnostic serum levels of thevitamin D metabolites, 25-hydroxyvitamin D (25-OH D), and1,25-dihydroxyvitamin D (1,25-DIOHD) were used as primary exposure measures.The baseline geometric-mean serum level of 25-OH D was 11.6 percent lower incases than in controls (12.2 cf 13.8 ug/l, P = 0.01) while serum levels of1,25-DIOH D did not differ by case-control status. No association was seenbetween serum levels of 1,25-DIOH D and large bowel cancer risk. However, theestimated relative risk (RR) of large bowel cancer decreased with increasinglevel of serum 25-OH D and the associa tion was more pronounced for rectalcancer (55 cases; RR by quartile = 1.00, 0.93, 0.77, 0.37; trend P = 0.06).Neither exclusion of early cases nor multivariate adjustment for potentialconfounders materially altered these estimates. There was no evidence ofeffect modification by level of 1,25-dihydroxyvitamin D or with other knownrisk-factors for large bowel cancer.
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Epidemiological and laboratory evidence suggest that vitamin D may play a role in reducing risk of breast cancer. Lack of exposure to ultraviolet sunlight can increase the prevalence of vitamin D deficiency, and may place some populations at higher risk of breast cancer. The association between total average annual sunlight energy striking the ground and age-adjusted breast cancer incidence rates in the USSR was evaluated. Breast cancer had a threefold range of incidence. Sunlight levels varied from 210 to 400 calories per cm2 per day. A statistically significant negative association was found between breast cancer incidence rates and total sunlight levels (R = −0.75, p = 0.001). The slope of the regression line corresponded to two additional cases per 100 000 per year for each reduction of 35 calories per cm2 of sunlight. The pattern of increased breast cancer incidence in regions of low solar radiation in the USSR is consistent with the geographical pattern seen for breast cancer mortality in the US and worldwide. A positive relationship between socioeconomic status and breast cancer incidence was also present in the Soviet Union, based on an approximate socioeconomic measure, the number of doctors per 1000 population (R = +0.89, p = 0.0001). The possibility that correlates of socioeconomic status, such as dietary, ethnic, or behavioural factors, could account for the association is discussed.
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Epidemiologic and laboratory evidence suggests that vitamin D may play a role in reducing breast cancer risk. Lack of exposure to ultraviolet sunlight can increase the prevalence of vitamin D deficiency. This deficiency may place some populations at higher risk for breast cancer. The association between total average annual sunlight energy striking the ground and age-adjusted breast cancer mortality rates in 87 regions of the United States was evaluated. Annual age-adjusted mortality rates for breast cancer varied over a 1.8-fold range, from 17-19 per 100,000 in the South and Southwest United States to 33 per 100,000 in the Northeast; the overall U.S. rate was 27.3 per 100,000. Risk of fatal breast cancer in the major urban areas of the United States was inversely proportional to intensity of local sunlight (r = -0.80, P = 0.0001); multiple regression with stratospheric ozone measurements, r = -0.82, P = 0.0001). Vitamin D from sunlight exposure may be associated with low risk for fatal breast cancer, and differences in ultraviolet light reaching the United States population may account for the striking regional differences in breast cancer mortality. The ecological nature of this study is emphasized, and the possibility that an indirect association with dietary and socioeconomic factors could explain these findings is discussed.
Article
Sulfur dioxide absorbs ultraviolet light in the region of the spectrum which is most active in forming vitamin D on the skin. Sulfate particles reflect light at this wavelength. High concentrations of these pollutants (acid haze) may lead to vitamin D deficiencies in exposed populations. Epidemiologic and laboratory evidence suggests that vitamin D plays a role in reducing risk of colon and breast cancer. We examined the association between sulfur dioxide and ultraviolet-light-blocking aerosols in 20 Canadian cities, and age-adjusted breast and colon cancer mortality rates in the census divisions encompassing these cities. Statistically significant positive associations were found between these two measures of air pollution and age-adjusted mortality rates for colon cancer in women (multiple r = +.74, p = 0.003), and men (multiple r = +.61, p = 0.03), and breast cancer in women (multiple r = +.69, p = 0.007). Mortality rates for all other reported cancer sites were also examined, and no statistically significant positive associations were found consistently in both sexes. The ecological nature of this study is emphasized, and the possibility that an indirect association could explain these findings is discussed.
Article
Sunlight has long been recognized as a major provider of vitamin D for humans; radiation in the UVB (290-315 nm) portion of the solar spectrum photolyzes 7-dehydrocholesterol in the skin to previtamin D3, which, in turn, is converted by a thermal process to vitamin D3. Latitude and season affect both the quantity and quality of solar radiation reaching the earth's surface, especially in the UVB region of the spectrum, but little is known about how these influence the ability of sunlight to synthesize vitamin D3 in skin. A model has been developed to evaluate the effect of seasonal and latitudinal changes on the potential of sunlight to initiate cutaneous production of vitamin D3. Human skin or [3 alpha-3H]7-dehydrocholesterol exposed to sunlight on cloudless days in Boston (42.2 degrees N) from November through February produced no previtamin D3. In Edmonton (52 degrees N) this ineffective winter period extended from October through March. Further south (34 degrees N and 18 degrees N), sunlight effectively photoconverted 7-dehydrocholesterol to previtamin D3 in the middle of winter. These results quantify the dramatic influence of changes in solar UVB radiation on cutaneous vitamin D3 synthesis and indicate the latitudinal increase in the length of the "vitamin D winter" during which dietary supplementation of the vitamin may be advisable.
Article
Mortality rates from colon cancer in the USA are highest in populations exposed to the least amounts of natural sunlight; differences in endogenous vitamin D production and calcium absorption could be responsible. To investigate this possibility, the association of dietary vitamin D and calcium with 19-year risk of colorectal cancer was examined in 1954 men who had completed detailed, 28-day dietary histories in the period 1957-59. Risk of colorectal cancer was inversely correlated with dietary vitamin D and calcium. In the quartiles of a combined index of dietary vitamin D and calcium, from lowest to highest, observed risks of colorectal cancer were 38.9, 24.5, 22.5, and 14.3/1000 population. This association remained significant after adjustment for age, daily cigarette consumption, body mass index, ethanol consumption, and percentage of calories obtained from fat.
Article
Garland CF (Department of Epidemiology, The Johns Hopkins University, School of Hygiene and Public Health, 615N Wolfe Street, Baltimore, Maryland 21205, USA) and Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer. International Journal of Epidemiology 1980, 9: 227–231. It is proposed that vitamin D is a protective factor against colon cancer. This hypothesis arose from inspection of the geographic distribution of colon cancer deaths in the U.S., which revealed that colon cancer mortality rates were highest in places where populations were exposed to the least amounts of natural light - major cities, and rural areas in high latitudes. The hypothesis is supported by a comparison of colon cancer mortality rates in areas that vary in mean daily solar radiation penetrating the atmosphere. A mechanism involving cholecalciferol (vitamin D3) is suggested. The possibility that an ecological fallacy or other indirect association explains the findings is explored.