Environmental Health Perspectives Volume
103, Supplement 8, November 1995
[Citation
in PubMed]
Overview of Ultraviolet Radiation and Cancer: What Is the Link? How
Are We Doing?
Martin A. Weinstock
Dermatoepidemiology Unit, VA Medical Center, Roger Williams Medical Center,
and Brown University, Providence, Rhode Island
Abstract
Sun exposure has now been established as the most important avoidable
cause of nonmelanoma skin cancer (NMSC) and melanoma. With specific reference
to melanoma, there are several key issues that remain to be resolved. These
include definition of the action spectrum, the importance of systemic effects
of sun exposure, whether a tan is protective, the risk of tanning booth
exposures, and the efficacy of sunscreens. Also the role, if any, of sun
exposure in noncutaneous malignancies remains to be established. Melanoma
incidence and mortality have increased dramatically over the past several
decades, but these increases have now slowed, and for mortality among those
15 to 45 years of age, decreasing rates are now observed. Improving the
coverage of the Surveillance, Epidemiology, and End Results (SEER) registries
by requiring pathology laboratories in non-SEER areas to report cancers
among SEER area residents will allow correct interpretation of these trends
in the future at minimal cost. The available data on trends in NMSC incidence
and mortality are suboptimal but suggest a pattern of declining mortality
despite increasing incidence. Trends in NMSC morbidity have not been defined.
Establishing NMSC registries in a few diverse sentinel areas would allow
more reliable inference and monitoring. Techniques are being developed for
reducing sun exposures and increasing early detection of skin cancers in
the general population, but improved monitoring of incidence, mortality,
and morbidity is required to monitor the effects of current and future ozone
depletion and to evaluate prevention and early detection measures. -- Environ
Health Perspect 103(Suppl 8):00-00 (1995)
Key words: ultraviolet rays, melanoma, basal cell carcinoma, squamous
cell carcinoma, incidence, mortality, morbidity, epidemiology, cancer registries
This article was presented at the President's Cancer Panel
Conference on Avoidable Causes of Cancer held 7-8 April 1994 in Bethesda,
Maryland. Manuscript received 9 March 1995; manuscript accepted 24 March
1995.
The author is supported by grants 49531 and 50087 from
the National Cancer Institute, grant 43051 from the National Institute
of Arthritis, Musculoskeletal, and Skin Disease, and the Department of
Veterans Affairs Medical Research Funds and Cooperative Studies Program.
Address correspondence to Dr. Martin A. Weinstock, Dermatoepidemiology
Unit, VA Medical Center #111D, 830 Chalkstone Avenue, Providence, RI 02908-4799.
Telephone: (401) 457-3333. Fax: (401) 457-3332. E-mail:
Martin_Weinstock_MD@brown.edu
Abbreviations used: NMSC, nonmelanoma skin cancer; SEER,
surveillance, epidemiology, and end results; BCC, basal cell carcinoma;
SCC, squamous cell carcinoma; UVA, ultraviolet A; UVB, ultraviolet B; UVC,
ultraviolet C; ICD, International Classification of Diseases.
Introduction
Ultraviolet radiation exposure has a variety of adverse health effects,
including both malignancies and nonmalignant disorders of the skin and other
organs. The most common ultraviolet-related malignancies are nonmelanoma
skin cancers (NMSCs), which, in the United States, are approximately equal
in incidence to all other malignancies combined (1). NMSC conventionally
includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC); the
former is more common, but the latter is more aggressive and more commonly
leads to death (2).
Malignant melanoma is less common than either BCC or SCC, but is of greater
public health concern. It is not uncommon; indeed, it is more common than
any noncutaneous malignancy in the 25- to 29- year-old age group, and its
incidence is increasing faster than any noncutaneous cancer site among men
and, with the exception of lung cancer, among women (3). More significantly,
it is responsible for approximately 7000 deaths per year, which is far greater
than the mortality associated with NMSC (4).
There are nonneoplastic disorders and other cutaneous malignancies that
have been linked to ultraviolet exposure, including atypical fibroxanthoma
(5); other dermatoses (6,7); immune dysfunction (8);
and ocular disease, particularly cataracts (9,10), but these will
not be further discussed here.
The Link
A vast array of epidemiologic and other investigations allows us to conclude
that sun exposure causes skin cancer of each of the three most common types:
BCC, SCC, and melanoma. Melanoma has been more closely linked to intense,
intermittent exposures to the sun, whereas NMSC is more closely linked to
cumulative exposure. However, this distinction is far from absolute; in
populations with high ultraviolet exposure, cumulative exposure may be closely
linked to melanoma (11,12). Sun exposures early in life, especially
in childhood and adolescence, are particularly associated with melanoma,
although such exposures are likely to play an important role in BCC and
SCC as well (13,14). Studies of special contexts (human models) have
been informative (15). Even in the context of familial melanoma and
of xeroderma pigmentosum, the very limited available evidence supports the
link between sun exposure and cutaneous malignancy (16-20).
Unresolved Issues
Ultraviolet light is not a single entity but rather a spectrum of electromagnetic
radiation that includes a broad band of wavelengths. Convention has defined
ultraviolet A (UVA) to include those wavelengths longer than 320 nm, ultraviolet
B (UVB) those in the range of 280 to 320 nm, and ultraviolet C (UVC) those
below 280 nm. UVC does not penetrate the earth's atmosphere, so human exposure
is a result of exposures to artificial sources. UVB is responsible for sunburns
and is the range most strongly blocked by common sunscreens. UVA, unlike
UVB, varies relatively little with solar elevation, and hence with the time
of day or season of the year. The various recommendations for skin cancer
prevention that have been offered to the general public differ in their
relative effectiveness for different ultraviolet wavelengths. For example,
clothing typically reduces ultraviolet exposure to the skin more uniformly
across the spectrum than avoiding the midday sun, which will disproportionately
reduce UVB exposure.
A key issue for each of the three common types of skin cancers is, therefore,
documentation of the action spectrum (i.e., the relation between carcinogenesis
and wavelength). Epidemiologic research has not been able to document an
action spectrum for any of these malignancies. Fortunately, there are well-established
animal models for SCC, which have been used to estimate the action spectrum.
These studies have documented maximal carcinogenicity in the UVB region
(21,22). Animal models have been proposed for melanoma; some action
spectrum data have been derived from a fish model, which suggests substantial
carcinogenic potential for UVA, but the relevance of these experiments to
the disorder in human remains to be clarified (23-26).
A second key unresolved issue is the relative importance of local versus
systemic effects of sun exposure. The majority of BCCs and of SCCs occur
on the chronically sun-exposed skin of the face, although most melanomas
occur elsewhere on the body, and the evidence from case-control studies
regarding melanomas that occur at common locations has not demonstrated
associations between location of sun exposure and location of the melanoma
(27-29). Among patients with xeroderma pigmentosum, NMSCs are more
concentrated on the face than melanomas (30). On the other hand,
the most sun-protected areas of the body do have the lowest incidence per
unit surface area of melanoma (12). It is also clear from the laboratory
that both local and systemic effects of ultraviolet exposure exist (8,31).
For anogenital or vaginal melanoma, where direct sun exposure is not involved,
populations with greater presumed cutaneous sun exposure because they live
nearer to equatorial latitudes do not have a higher incidence (32,33).
Hence, epidemiologic evidence has not be able to completely resolve the
relative importance of a systemic effect, if any, of sun exposure on the
genesis of melanoma, although direct exposure appears to be important.
A third key unresolved issue is whether a tan (facultative pigmentation)
protects against melanoma for some groups. It is clear that individuals
with darker untanned skin color (constitutive pigmentation) are at substantially
lower risk of melanoma. Suntans also protect against sunburn, which is associated
with melanoma risk (34). There have now been several studies published
that suggest that frequent sun exposure may be associated with lower relative
risks among those who tan readily (presumably as a result of their developing
a photoprotective tan) compared to the relative risks of similar exposures
among those who are more sun sensitive and less capable of tanning; however,
this hypothesis remains controversial (28,35-38).
The risk of melanoma associated with exposure to artificial sources of
ultraviolet is also uncertain. Several, but not all, studies of this question
have noted an association between these exposures and melanoma risk (39,40).
The fourth issue is the efficacy of sunscreens for melanoma prevention.
We know from trials among human populations that conventional sunscreens
are efficacious for preventing sunburns and for reducing the multiplicity
of actinic keratoses (41). However, we have no direct evidence, from
either animal models or human studies, about their efficacy for melanoma
prevention. Indeed, one publication has even suggested that sunscreen use
causes melanoma and was responsible for the sharp rise in melanoma incidence
observed over the last several decades (42), although this suggestion
is not supported by any substantial evidence and does not fit with our current
understanding of the genesis of melanoma. Hence, although we presume that
sunscreens are effective, we do not have proof and cannot presently quantify
their effectiveness.
Finally, the role of sun exposure, if any, in noncutaneous malignancies
has not been established. A number of cancer sites exhibit a latitude gradient
that is presently unexplained. However, there is no strong evidence to support
a role for the sun in the etiology of any noncutaneous malignancy, except
perhaps as a cause of ocular malignancy due to direct exposure.
These half dozen issues represent key areas of uncertainty in our understanding
of the link between the ultraviolet radiation and cutaneous malignancy.
The list is not comprehensive, and it focuses on those issues that pertain
to melanoma. The uncertainties stand out against a background of general
acceptance of sun exposure as the major avoidable cause of melanoma, accounting
for over 90% of the melanomas in the United States and about two-thirds
of the melanomas worldwide (43).
Current Trends--Melanoma
Age-adjusted mortality rates for malignant melanoma in the United States
have been increasing consistently over many decades and continued to increase
throughout the 1980s. This increase occurred among whites but not blacks.
In 1990 the rate among whites was 2.5 per 100,000 individuals per year,
and among blacks 0.4 per 100,000 individuals per year. Age-adjusted melanoma
incidence has also been increasing among whites since at least the 1930s,
and is now over 10 times more common than it was. In recent years, the incidence
has been more than 12 times higher among whites (12.0 per 100,000 individuals
per year) than among blacks (0.9 per 100,000 individuals per year) (3).
Some stratospheric ozone depletion has occurred since the 1930s, but
that appears to have contributed little to the present increase in melanoma
because the magnitude of the depletion has been quite modest. Rather, the
observed increases in both incidence and mortality appear to be most closely
linked to behavioral and lifestyle factors, including the popularity of
tanning and the corresponding unpopularity of pale skin among whites, the
changing styles of dress in general and recreational (particularly beach)
attire in particular, the increase in leisure time during these decades,
and the increased accessibility of recreation in areas of intense sunlight
because of the widespread availability of automobiles and air travel.
Past trends will not necessarily continue, however, and recent data provide
evidence that these trends may indeed change. Age-specific mortality data
were evaluated for the years 1969 through 1990 for whites in the United
States. Despite an overall increase in mortality during this period, the
youngest age groups (ages 15-29 years and 30-44 years) experienced declines
in mortality for both genders (44). These data have been used to
project an actual decline in age-adjusted melanoma mortality in the second
decade of the 21st century (45,46). Without understanding the cause
of the current trends, however, predictions regarding future trends must
be viewed cautiously.
It is clear that case fatality from melanoma has declined substantially
despite the absence of major therapeutic advances. This decline undoubtedly
played an important role in the observed changes in mortality. However,
the role of changes in incidence remains unclear.
The primary source of melanoma incidence data in the United States is
the SEER Program of the National Cancer Institute. Despite the general excellence
of the SEER program, it has encountered difficulties in recent years in
attaining complete registration of melanoma (47-50). As a result,
the observed pattern in the SEER data of relatively stable incidence rates
must be interpreted with care.
Among these issues, out-of-area diagnosis may be the most difficult problem
for a disorder such as melanoma, which is cured in the majority of patients
and frequently diagnosed and cured in an outpatient setting. Dermatologists
frequently biopsy a skin lesion to diagnose melanoma. They typically excise
the melanoma in their offices, and then mail the specimen to a pathology
laboratory. If the pathology laboratory is in the cancer registry area and
the registry is functioning properly, these cases will be registered. However,
the pathology laboratory sometimes is located outside the registry area,
in which case the cancer registry may miss the case entirely. This trend
toward outpatient and out-of-area diagnosis threatens the usefulness of
the existing system of cancer registries in guiding policy, practice, and
research for cancers that are commonly diagnosed among outpatients.
Were a national cancer registry to be developed, this problem would largely
disappear. However, much less expensive alternatives are available. It would
be sufficient to require that pathology laboratories in non-SEER areas record
their patients' zip codes and report the cancers that occur among SEER area
residents. Effort and expense involved in this approach would be minimal,
yet would be essential to guarantee the integrity of the SEER registry data
in the current changing health care climate.
Current Trends--NMSC
NMSCs as a group have a case fatality rate of less than 1%; however,
this low percentage still results in over a thousand deaths annually because
of the frequency with which these malignancies occur. Unfortunately, NMSC
mortality is poorly tracked by our vital statistics in the United States.
We recently investigated over 100 deaths among residents of Rhode Island
that were attributed to NMSC by vital statistics data. Over half of these
deaths were misclassified, and the majority of misclassified cases were
instances of squamous carcinoma of the mucosal surfaces in the head and
neck. These cases were described on death certificates as dying from squamous
or epidermoid carcinoma of the head and neck and the coding rules assigned
them the code 173.4, which incorrectly classified the cause of death as
NMSCs. Therefore, to obtain accurate mortality estimates for NMSC, it is
recommended that the International Classification of Diseases (ICD) coding
system be modified to exclude squamous cell carcinoma of the head and neck
and other similar terms from code 173.4 (the NMSCs of the scalp and neck).
Extrapolation from our observations to the existing nationwide statistics
regarding NMSC mortality suggested that the mortality rate from this cause
has indeed been declining over the past two decades. The age-adjusted rates
for whites and blacks for 1987 to 1988, which is the most recent published
data, were 0.5 and 0.3 per 100,000 individuals per year, and the rate among
men was substantially higher than that among women (51).
Data regarding the incidence of NMSC is also quite limited compared with
corresponding data on melanoma. The only available data from diverse areas
of the United States are from a 17-year-old study of the National Cancer
Institute. Since sun exposure accounts for the vast majority of NMSCs as
well as melanomas, one would expect NMSC incidence to be increasing substantially
in recent decades. This expectation was confirmed by data from the British
Columbia Cancer Registry and from Kaiser-Permanente data from Oregon. Extrapolation
of these trends to the entire U.S. population suggested that 900,000 to
1,200,000 persons would be diagnosed with NMSC nationwide in 1994 (1).
Approximately this many people are diagnosed with all other types of cancer
combined. This projection may be subject to considerable error, but it is
presently the best available estimate because NMSC is not included in standard
U.S. cancer registries. Registration of NMSC in a few diverse sentinel areas,
therefore, would be crucial for understanding future trends in the incidence
of NMSC, particularly in view of ozone depletion and public health campaigns
for prevention and early detection of cancer.
Since NMSC is so common, morbidity becomes a key component of its public
health impact. In individual cases, morbidity ranges from quite minor to
severe, which can include the loss or impairment of vital facial structures
such as eyes, ears, or the nose. There is at present no published method
for assessing NMSC morbidity among the general population, although one
is under development in our unit. Use of morbidity data will become increasingly
important in the assessment of the public health impact of this disorder.
Conclusions
Actual ultraviolet exposure received by the general population is affected
both by the flux in the environment--which in turn is a function of
stratospheric ozone depletion, cloud cover, artificial cover, surface albedo,
altitude and latitude--and by behaviors of the populations exposed. Significant
progress is being made in understanding how to affect behaviors of high
risk populations, but more accurate monitoring of incidence, morbidity,
and mortality will be required to assess the effects of these factors on
the public health burden from skin cancers.
REFERENCES
1. Miller DL, Weinstock MA. Nonmelanoma skin cancer in
the United States: incidence. J Am Acad Dermatol 30:774-778 (1994).
2. Weinstock MA, Bogaars HA, Ashley M, Litle V, Bilodeau
E, Kimmel S. Nonmelanoma skin cancer mortality: a population-based study.
Arch Dermatol 127:1194-1197 (1991).
3. Miller BA, Ries LAG, Hankey BF, Kosary CL, Harras A,
Devesa SS, Edwards BK, eds. SEER Cancer Statistics Review, 1973-1990. NIH
Publ No 93-2789. Bethesda, MD:National Institutes of Health, 1993.
4. Boring CC, Squires TS, Tong T, Montgomery S. Cancer
statistics, 1994. CA Cancer J Clin 44:7-26 (1994).
5. Dei Tos AP, Maestro R, Doglioni C, Gasparotto D, Boiocchi
M, Laurino L, Fletcher CD. Ultraviolet-induced p53 mutations in atypical
fibroxanthoma. Am J Pathol 145:11-17 (1994).
6. Council on Scientific Affairs. Harmful effects of ultraviolet
radiation. JAMA 262:380-384 (1989).
7. Taylor CR, Stern RS, Leyden JJ, Gilchrest BA. Photoaging/photodamage
and photoprotection. J Am Acad Dermatol 22:1-15 (1990).
8. Baadsgaard O. In vivo ultraviolet irradiation
of human skin results in profound perturbation of the immune system: relevance
to ultraviolet-induced skin cancer. Arch Dermatol 127:99-109 (1991).
9. Cruickshanks KJ, Klein R, Klein BEK. Sunlight and age-related
macular degeneration: the Beaver Dam Eye Study. Arch Ophthalmol 111:514-518
(1993).
10. Taylor HR. The biological effects of UVB on the eye.
Photochem Photobiol 50:489-492 (1989).
11. Elwood JM. Melanoma and sun exposure: contrasts between
intermittent and chronic exposure. World J Surg 16:157-166 (1992).
12. Green A, MacLennan R, Youl P, Martin N. Site distribution
of cutaneous melanoma in Queensland. Int J Cancer 53:232-236 (1993).
13. Weinstock MA. Ultraviolet radiation and skin cancer:
epidemiologic data from the United States and Canada. In: Environmental
UV Photobiology (Young AR, Bjîrn LO, Moan J, Nultsch W, eds). New
York:Plenum Press, 1993;295-344.
14. Armstrong BK, Kricker A. Skin cancer. Dermatol Clin
13:583-594 (1995).
15. Weinstock MA. Human models of melanoma. Clin Dermatol
10:83-89 (1992).
16. Kraemer KH, Greene MH. Dysplastic nevus syndrome: familial
and sporadic precursors of cutaneous melanoma. Dermatol Clin 3:225-237 (1985).
17. Lynch HT, Frichot BC, Lynch JF. Cancer control in xeroderma
pigmentosum. Arch Dermatol 113:193-195 (1977).
18. Davis BE, Koh HK, Rohrer TE, González E, Cleaver
JE. Sunlight avoidance and cancer prevention in xeroderma pigmentosum. Arch
Dermatol 130:806-808 (1994).
19. Cox SE, Roberts LJ, Bergstresser PR. Prevention of
skin cancer in xeroderma pigmentosum: the physician as advocate. J Am Acad
Dermatol 29:1045-1046 (1993).
20. Bech-Thomsen N, Wulf HC, Ullman S. Xeroderma pigmentosum
lesions related to ultraviolet transmittance by clothes. J Am Acad Dermatol
24:365-368 (1991).
21. de Gruijl FR, Sterenborg HJ, Forbes PD, Davies RE,
Cole C, Kelfkens G, van Weelden H, Slaper M, van der Leun JC. Wavelength
dependence of skin cancer induction by ultraviolet irradiation of albino
hairless mice. Cancer Res 53:53-60 (1993).
22. Cole CA, Forbes D, Davies RE. An action spectrum for
UV photocarcinogenesis. Photochem Photobiol 43:275-284 (1986).
23. Ley RD, Applegate LA, Padilla RS, Stuart TD. Ultraviolet
radiation-induced malignant melanoma in Monodelphis domestica. Photochem
Photobiol 50:1-5 (1989).
24. Setlow RB, Grist E, Thompson K, Woodhead AD. Wavelengths
effective in induction of malignant melanoma. Proc Natl Acad Sci USA 90:6666-6670
(1993).
25. Klein-Szanto AJP, Silvers WK, Mintz B. Ultraviolet
radiation-induced malignant skin melanoma in melanoma-susceptible transgenic
mice. Cancer Res 54:4569-4572 (1994).
26. Epstein JH. Experimental models for primary melanoma.
Photodermatol Photoimmunol Photomed 9:91-98(1992).
27. Green A, Bain C, McLennan R, Siskind V. Risk factors
for cutaneous melanoma in Queensland. Recent Results Cancer Res 102:76-97
(1986).
28. Weinstock MA, Colditz GA, Willett WC, Stampfer MJ,
Bronstein BR, Mihm MC Jr, Speizer FE. Melanoma and the sun: the effect of
swim suits and a "healthy" tan on the risk of nonfamilial malignant
melanoma in women. Am J Epidemiol 134:462-470 (1991).
29. Lee JAH, Merrill JM. Sunlight and the etiology of malignant
melanoma: a synthesis. Med J Aust 2:846-851 (1970).
30. Kraemer KH, Lee MM, Andrews AD, Lambert WC. The role
of sunlight and DNA repair in melanoma and nonmelanoma skin cancer: the
xeroderma pigmentosum paradigm. Arch Dermatol 130:1018-1021 (1994).
31. Stierner U, Rosdahl I, Augustsson A, Kagedal B. UVB
irradiation induces melanocyte increase in both exposed and shielded human
skin. J Invest Dermatol 92:561-564 (1989).
32. Weinstock MA. Epidemiology and prognosis of anorectal
melanoma. Gastroenterology 104:174-178 (1993).
33. Weinstock MA. Malignant melanoma of the vulva and vagina
in the United States: patterns of incidence and population-based estimates
of survival. Am J Obstet Gynecol 171:1225-1230 (1994).
34. Weinstock MA, Colditz GA, Willett WC, Stampfer MJ,
Bronstein BR, Mihm MC Jr, Speizer FE. Nonfamilial cutaneous melanoma incidence
in women associated with sun exposure before 20 years of age. Pediatrics
84:199-204 (1989).
35. Dubin N, Mosseson M, Pasternack BS. Sun exposure and
malignant melanoma among susceptible individuals. Environ Health Perspect
81:139-151 (1989).
36. White E, Kirkpatrick CS, Lee JAH. Case-control study
of malignant melanoma in Washington State. 1: constitutional factors and
sun exposure. Am J Epidemiol 139:857-868 (1994).
37. Nelemans PJ, Groenendal H, Kiemeney LALM, Rampen FHJ,
Ruiter DJ, Verbeek ALM. Effect of intermittent exposure to sunlight on melanoma
risk among indoor workers and sun-sensitive individuals. Environ Health
Perspect 101:252-255 (1993).
38. Herzfeld PM, Fitzgerald EF, Hwang SA, Stark A. A case-control
study of malignant melanoma of the trunk among white males in upstate New
York. Cancer Detect Prev 17:601-608 (1993).
39. Walter SD, Marrett LD, From L, Hertzman C, Shannon
HS, Roy P. The association of cutaneous malignant melanoma with the use
of sunbeds and sunlamps. Am J Epidemiol 131:232-243 (1990).
40. Westerdahl J, Olsson H, Måsbäck A, Ingvar
C, Jonsson N, Brandt L, Jonsson PE, Muller T. Use of sunbeds or sunlamps
and malignant melanoma in southern Sweden. Am J Epidemiol 140:691-699 (1994).
41. Thompson SC, Jolley D, Marks R. Reduction of solar
keratoses by regular sunscreen use. N Engl J Med 329:1147-1151 (1993).
42. Garland CF, Garland FC, Gorham ED. Rising trends in
melanoma: a hypothesis concerning sunscreen effectiveness. Annu Epidemiol
3:103-110 (1993).
43. Armstrong BK, Kricker A. How much melanoma is caused
by sun exposure? Melanoma Res 3:395-401 (1993).
44. Weinstock MA. Epidemiology of melanoma. In: Current
Research and Clinical Management of Melanoma (Nathanson L, ed). Boston:Kluwer
Academic Publishers, 1993;29-56.
45. Scotto J, Pitcher H, Lee JAH. Indications of future
decreasing trends in skin-melanoma mortality among whites in the United
States. Int J Cancer 49:490-497 (1991).
46. Roush GC, McKay L, Holford TR. A reversal in the long-term
increase in deaths attributable to malignant melanoma. Cancer 69:1714-1720
(1992).
47. Karagas MR, Thomas DB, Roth GJ, Johnson LK, Weiss NS.
The effects of changes in health care delivery on the reported incidence
of cutaneous melanoma in western Washington State. Am J Epidemiol 133:58-62
(1991).
48. Wright M. Underreporting of melanoma gives false sense
of security. Dermatology Times. August 1991;45.
49. Koh HK, Geller A, Miller DR, Clapp RW, Lew RA. Underreporting
of cutaneous melanoma in cancer registries nationwide. J Am Acad Dermatol
27:1035-1036 (1992).
50. Bolognia JL, Headley A, Fine J, Berwick M. Histologic
evaluation of pigmented lesions in Connecticut and its influence on
the reporting of melanoma. J Am Acad Dermatol 26:198-202 (1992).
51. Weinstock MA. Nonmelanoma skin cancer mortality in
the United States, 1969 through 1988. Arch Dermatol 129:1286-1290 (1993).
[
Table
of Contents]
Last Update: September 8, 1998
