A Swedish cohort analysis in this issue (1) demonstrates a significant reduction in all cause mortality and in cardiovascular mortality associated with several measures of sun exposure. In addition, ultraviolet exposure from tanning beds is associated with a significant increase in all cause mortality and cancer mortality. A potential explanation for the protective association is that UV exposure results in high levels of serum vitamin D which may improve survival. However, that explanation does not hold for ultraviolet exposure from tanning beds, which in this study is associated with a significant increase in all cause mortality and cancer mortality. Such a finding is curious and inconsistent with a vitamin D hypothesis. These results should impel investigators to study further the biology of ultraviolet radiation, both natural and artificial, and its health effects. Cancer Epidemiol Biomarkers Prev; 20(4); 582–4. ©2011 AACR.

Commentary on Yang et al., p. 683

Poison is in everything, and no thing is without poison. The dosage makes it either a poison or a remedy.

Paracelsus

There has been much discussion in the literature as to the benefits and risks of UV exposure, both natural and artificial. The risks of excess UV exposure focus on skin cancer and the benefits on vitamin D. However, a very recent Institute of Medicine report (2) clearly states that “there is not sufficient evidence to establish a relationship between vitamin D and health outcomes other than bone health” and that the recommendations are based on minimal solar exposure (i.e., almost none). A new article in this issue of Cancer Epidemiology, Biomarkers & Prevention (1) demonstrates both beneficial and harmful effects from different forms of UV exposure—natural and artificial–in a prospective study of 38,472 women in Sweden who were followed for 15 years. Among this group, 754 deaths occurred—457 from cancer and 100 from cardiovascular disease. Overall mortality was reduced among those who had been sunburned 2 or more times a year as teenagers compared with those who had been sunburned 1 or fewer times (HR = 0.7; 95% CI 0.5–0.9). In addition, overall mortality and CVD mortality was reduced (HR = 0.7, 95% CI 0.6–0.9; HR = 0.5, 05% CI 0.3–0.8, respectively) among those who had taken sunbathing vacations more than once a year during 3 decades. Conversely solarium use once or more per month for at least a decade increased the risk of all cause deaths compared with those who never used solaria (HR = 1.9; 95% CI, 1.3–2.7) as well as total cancer deaths (HR 1.6; 95% CI, 1.0, 2.8). The study has an excellent design (a prospective cohort), repeated measures of sun exposure and diet and is able to control for a number of potential confounders, such as pigmentation, BMI, education, and exercise. These results are likely to be controversial, but understanding their biological basis will be critical to evaluate the risks and benefits of UV exposure.

Due to the lack of strong data for the relationship between UV exposure and serum vitamin D, it is difficult to draw conclusions about the rationale for the effects seen in the Yang and colleagues paper (1) where 2 of multiple measures of sun exposure in a prospective cohort are associated with improved overall mortality and improved cardiovascular mortality. However, it should be pointed out that the lack of an association for these measures in relationship to cancer mortality is not inconsistent with varied studies to date, ecological, and prospective (e.g., 3). It may be that different measures than those used by Yang and colleagues are inversely associated with cancer mortality, such as solar elastosis and serum vitamin D (e.g., 4–6).

Intermittent UV and melanoma risk

Meta-analyses of the many studies conducted on the role of solar UV exposure and melanoma etiology are highly consistent and demonstrate an increased risk of approximately 1.6 for the development of melanoma with high levels of intermittent sun exposure (7–9). Within this cohort Veierod had previously found an increased risk between UV exposure, both natural and artificial, and the development of melanoma (10). Thus, the study itself is internally consistent with known effects of UV. Artificial UV exposure clearly increases risk for melanoma and nonmelanoma skin cancer (11) as has been demonstrated in ecological (12), case–control (13), and cohort studies (10). Conversely, it is well established that chronic sun exposure does not increase risk for developing melanoma although the mechanism for that observation is unclear (7–9).

Benefits from UV exposure

Although the risks for skin cancer from excessive sun exposure are well known, the benefits from UV exposure are less well known. Yang and colleagues (1) found an inverse association between measures of sun exposure and overall mortality and mortality from cardiovascular disease. They suggested that one mode of action was through UV and serum vitamin D. There is a large literature developing on the relationship between UV exposure or serum vitamin D and disease. The evidence for an inverse association between serum vitamin D and cancer risk is equivocal and strongest for colorectal cancer (e.g., 14). The association with mortality is also inconsistent, with some cohort studies indicating that high levels of serum vitamin D associated with improved survival (15) and some indicating a need for caution (16). There are many substantiated benefits from attaining optimal vitamin D levels: rickets among the young and bone fractures among the elderly. Optimal levels have yet to be clearly defined. The IOM report found no evidence for maintaining serum vitamin D levels above 30 ng/mL, or 50 nmol/L, which is in direct opposition to many investigators who are promulgating much higher levels (e.g., 17).

Noncancer disease incidence and mortality has also been previously related to higher serum vitamin D levels. As cardiovascular disease-related deaths are anticipated to increase by 80% among females by 2020, this area is important for investigation (18). Among patients with end stage renal disease, 1 alpha-vitamin D and paricalcitol are effective drugs to reduce mortality risk from cardiovascular disease (19–21). Excess parathyroid hormone (associated with low levels of serum vitamin D) increases blood pressure and contributes to cardiovascular disease. Zittermann (19) points out the relatively strong inverse and statistically significant association between ischemic heart disease death rates in Europe and latitude, as a proxy for UV exposure and serum vitamin D levels, 0.49 for females and 0.51 for males.

On the other hand, it is possible that UV exposure may have potential benefits that do not accrue through serum vitamin D. Lucas and Ponsonby (22) concluded that “although the major beneficial effect of UV is as the major source of serum vitamin D, it is not clear that maintaining sun avoidance by supplementing vitamin D will be sufficient to avoid the risks of too little exposure to UV.” Increased UV exposure has multiple pathways that serve to protect from disease: endocrine function (23), direct immunosuppression (e.g, 24); immunosuppression due to inhibition of melatonin production (e.g., 25); increased serotonin turnover (e.g., 26); increased alpha melanocyte stimulating hormone (e.g, 27); increased DNA repair capacity (e.g, 28); as well as therapeutic effects on psoriasis (e.g, 29), eczema (e.g, 30), and vitiligo (e.g, 31). Further, evidence for a benefit from UV exposure is relatively strong for autoimmune diseases. Multiple sclerosis (MS) has been shown in ecological studies to have generally greater incidence and prevalence at higher latitudes (32) and analytic studies demonstrate that higher overall UV exposure is inversely associated with MS (e.g., 33). Type I diabetes also shows a latitudinal gradient such that there is a higher incidence at higher latitudes (34).

Sunbeds and increased mortality

The surprising finding that sunbed use is assoicated with increased mortality is not yet explained, and so it may be worth additional speculation. One suspects unmeasured or residual confounding not accounted for by the lifestyle factors controlled in analyses, such as education as a proxy for socioeconomic status. It may, for example, be plausible that there are individuals without the means to take any vacations who use solaria as a substitute for the perceived benefits from sunny holidays abroad. In addition, existing comorbidities may prevent holidays but not solaria use, and these could potentially confound the results. This finding needs replicaton and should support additional study to understand the mechanism for the association found.

Summary

Lack of information on the association between UV radiation and vitamin D or other hormonal and endocrine effects hampers the ability to precisely explain the results of Yang and colleagues (1). However, even with that caveat, these results are likely to add to the weight of the evidence for benefits from sun exposure and risks associated with indoor tanning.

No potential conflicts of interest were disclosed.

1.
Yang
L
,
Lof
M
,
Veierod
MB
,
Sandin
S
,
Adami
H-O
,
Weiderpass
E
. 
Ultraviolet exposure and mortality among women in Sweden
.
Cancer Epidemiol Biomarkers Prev
2011
;
20
:
683
90
.
2.
Ross
CA
,
Taylor
CL
,
Yaktine
AL
,
Dell Valle
HB
(
eds
). 
Committee to Review Dietary Reference Intakes for Vitamin D and Calcium
.
Institute of Medicine, National Academy Press
,
Washington, DC
, 
2010
.
3.
Boscoe
FP
,
Schymura
MJ
. 
Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993–2002
.
BMC Cancer
2006
;
6
:
264
.
4.
Newton-Bishop
JA
,
Beswick
S
,
Randerson-Moor
J
,
Chang
YM
,
Affleck
P
,
Elliott
F
, et al
Serum 25-hydroxyvitamin D3 levels are associated with breslow thickness at presentation and survival from melanoma
.
J Clin Oncol
2009
;
27
:
5439
44
.
5.
Rosso
S
,
Sera
F
,
Segnan
N
,
Zanetti
R
. 
Sun exposure prior to diagnosis is associated with improved survival in melanoma patients: results from a long-term follow-up study of Italian patients
.
Eur J Cancer
2008
;
44
:
1275
81
.
6.
Berwick
M
,
Armstrong
BK
,
Ben-Porat
L
,
Fine
J
,
Kricker
A
,
Eberle
C
,
Barnhill
R
. 
Sun exposure and mortality from melanoma
.
J Natl Cancer Inst
2005
;
97
:
195
9
.
7.
Gandini
S
,
Sera
F
,
Cattaruzza
MS
,
Pasquini
P
,
Picconi
O
,
Boyle
P
, et al
Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure
.
Eur J Cancer
2005
;
41
:
45
60
8.
Elwood
JM
,
Jopson
J
. 
Melanoma and sun exposure: an overview of published studies
.
Int J Cancer
1997
;
73
:
198
203
.
9.
Nelemans
PJ
,
Rampen
FHJ
,
Ruiter
DJ
,
Verbeek
ALM
. 
An addition to the controversy on sunlight exposure and melanoma risk: A meta-analytical approach
.
J Clin Epidemiol
1995
;
58
:
1331
42
10.
Veierød
MB
,
Adami
HO
,
Lund
E
,
Armstrong
BK
,
Weiderpass
E
. 
Sun and solarium exposure and melanoma risk: effects of age, pigmentary characteristics, and nevi
.
Cancer Epidemiol Biomarkers Prev
2010
;
19
:
111
20
.
11.
International Agency for Research on Cancer Working Group on artificial ultraviolet (UV) light and skin cancer
. 
The association of use of sunbeds with cutaneous malignant melanoma and other skin cancers: A systematic review
.
Int J Cancer
2007
;
120
:
1116
22
12.
Héry
C
,
Tryggvadóttir
L
,
Sigurdsson
T
,
Olafsdóttir
E
,
Sigurgeirsson
B
,
Jonasson
JG
, et al
A melanoma epidemic in Iceland: possible influence of sunbed use
.
Am J Epidemiol
2010
;
172
:
762
7
.
13.
Lazovich
D
,
Vogel
RI
,
Berwick
M
,
eMA
,
Anderson
KE
,
Warshaw
EM
. 
Indoor tanning and risk of melanoma: A case-control study in a highly exposed population
.
Cancer Epidemiol Biomarkers Prev
2010
;
19
:
1557
68
14.
Gonzalez
CA
,
Riboli
E
. 
Diet and cancer prevention: Contributions from the European Prospective Investigation into Cancer and Nutrition (EPIC) study
.
Eur J Cancer
2010
;
46
:
2555
62
.
15.
Virtanen
JK
,
Nurmi
T
,
Voutilainen
S
,
Mursu
J
,
Tuomainen
TP
. 
Association of serum 25-hydroxyvitamin D with the risk of death in a general older population in Finland
.
Eur J Nutr
2010
;
epub ahead of press
.
16.
Freedman
DM
,
Looker
AC
,
Abnet
CC
,
Linet
MS
,
Graubard
BI
. 
Serum 25-hydroxyvitamin D and cancer mortality in the NHANES III study (1988–2006)
.
Cancer Res
2010
;
70
:
8587
97
.
17.
Bischoff-Ferrari
HA
. 
Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes
.
Adv Exp Med Biol
2008
;
624
:
55
71
.
18.
Lucas
RM
,
Ponsonby
A-L
. 
Considering the potential benefits as well as adverse effects of sun exposure: Can all the potential benefits be provided by oral vitamin D supplementation?
Progr Biophysics Mol Biology
2006
;
92
:
140
9
.
19.
Yusuf
S
,
Reddy
S
,
Ounpuu
S
,
Anand
S
. 
Global burden of cardiovascular diseases: part II: Variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies
.
Circulation
2001
;
104
:
2855
64
.
20.
Zitterman
A
. 
Vitamin D and disease prevention with special reference to cardiovascular disease
.
Prog Biophys Mol Biology
2006
;
92
:
39
48
.
21.
Shoji
T
,
Shinohara
K
,
Kimoto
E
,
Emoto
M
,
Tahara
H
,
Koyama
H
, et al
Lower risk for cardiovascular mortality in oral 1 alpha-hydroxy vitamin D3 users in a haemodialysis population
.
Nephrol Dial Transplant
2004
;
19
:
179
84
.
22.
Teng
M
,
Wolf
M
,
Ofsthun
N
,
Lazarus
JM
,
Hernan
MA
,
Camargo
CA
 Jr
, et al
Activated injectable vitamin D and hemodialysis survival: a historical cohort study
.
J Am Soc Nephrol
2005
;
16
:1
115
25
.
23.
Studzinski
GP
,
Moore
DC
. 
Sunlight – can it prevent as well as cause cancer?
Cancer Res
1995
;
55
:
4014
22
.
24.
Halliday
GM
,
Byrne
SN
,
Kuchel
JM
,
Poon
TS
,
Barnetson
RS
. 
The suppression of immunity by ultraviolet radiation: UVA, nitric oxide and DNA damage
.
Photochem Photobiol Sci
2004
;
3
:
736
40
.
25.
Liebmann
PM
,
Wolfler
A
,
Felsner
P
,
Hofer
D
,
Schavenstein
K
. 
Melatonin and the immune system
.
Int Arch Allergy Immunol
1997
;
112
:
203
11
.
26.
Lambert
GW
,
Reid
C
,
Kaye
DM
,
Jennings
GL
,
Esler
MD
. 
Effect of sunlight and season on serotonin turnover in the brain
.
Lancet
2002
;
360
:
1840
42
.
27.
Sieffert
K
,
Granstein
RD
. 
Neuropeptides and neuorendocrine hormones in ultraviolet radiation-induced immunosuppression
.
Methods
2002
;
28
:
97
103
.
28.
Gilchrest
BA
,
Eller
MS
. 
DNA photodamage stimulates melanogenesis and other photoprotective responses
.
J Investig Dermatol Symp Proc
1999
;
4
:
35
40
.
29.
Johnson-Huang
LM
,
Suárez-Fariñas
M
,
Sullivan-Whalen
M
,
Gilleaudeau
P
,
Kruegen
IG
,
Lowes
MA
. 
Effective narrow-band UVB radiation therapy suppresses the IL-23/IL-17 axis in normalized psoriasis plaques
.
J Invest Dermatol
2010
;
130
:
2654
63
.
30.
Reynolds
NJ
,
Franklin
V
,
Gray
JC
,
Diffey
BL
,
Farr
PM
. 
Narrow-band ultraviolet B and broad-band ultraviolet A phototherapy in adult atopic eczema: a randomised controlled trial
.
Lancet
2001
;
357
:
2012
16
.
31.
Akar
A
,
Tunca
M
,
Koc
E
,
Kurumlu
Z
. 
Broadband targeted UVB phototherapy for localized vitiligo: a retrospective study
.
Photodermatol Photoimmunol Photomed
2009
;
25
:
161
3
.
32.
McMichael
AJ
,
Hall
AJ
. 
Multiple sclerosis and ultraviolet radiation: time to shed more light
.
Neuroepidemiology
2001
;
20
:
165
7
.
33.
Staples
J
,
Ponsonby
AL
,
Lim
L
. 
Low maternal exposure to ultraviolet radiation in pregnancy, month of birth, and risk of multiple sclerosis in offspring: longitudinal analysis
.
BMJ
2010
;
340
:
c1640
.
34.
Shapira
Y
,
Agmon-Levin
N
,
Shoenfeld
Y
. 
Defining and analyzing geoepidemiology and human autoimmunity
.
J Autoimmun
2010
;
34
:
168
77
.

Supplementary data