CHAPTER 9

CORRELATIONS WITH INDICATORS OF CUMULATIVE SUN EXPOSURE

The results from the ecological studies of melanoma and latitude led to case-control studies which further investigated the hypothesis that exposure to UV radiation is causally associated with cutaneous malignant melanoma (CMM) using estimates of cumulative sun exposure. The estimates of sun exposure were defined somewhat differently from study to study, but all were based on individual interviews or questionnaires and, as such, provided an assessment of individual exposure. Two early studies (Lancaster and Nelson 1957; Gellin et al. 1969) might be considered crude by current epidemiologic standards, but they are historically important to the development and exploration of the hypothesis. Three other case-control studies of CMM investigated total or cumulative sun exposure in Western Australia (Holman and Armstrong 1984a, b; Holman et al. 1986), in Queensland, Australia (Green 1984), and in Western Canada (Elwood et al. 1985). The Western Australia and Western Canada studies are the largest case-control studies of CMM to date, and unlike most other studies, they controlled for important confounding variables, such as pigmentary factors.

An early case-control study of melanoma in Sydney, Australia (Lancaster and Nelson 1957) estimated total sun exposure by means of a scoring index based on: length of life in Australia, occupational exposure, industrial hazards, war service, and outdoor sports. This study is of historical importance because it was the first epidemiologic study of CMM to measure sun exposure in individuals. Interview results from 173 CMM cases, 173 non-melanoma skin cancer controls (age- and sex-matched to the cases), and 173 non-skin cancer controls (also age- and sex-matched to the melanoma cases) showed a higher proportion of melanoma cases with "excessive" sun exposure (26.6 percent) as compared with the other skin-cancer controls (21.4 percent) and the non-skin cancer controls (16.2 percent). The authors concluded that this finding, in addition to others, supported the hypothesis that sun exposure is an important factor in the occurrence of CMM.

Gellin et al. (1969) analyzed data from interviews of 79 cutaneous melanoma cases and 1,037 unmatched controls (non-tumor skin conditions) from 1955 to 1967 in New York. Results showed that 68 percent of the melanoma patients reported spending three or more hours per day outdoors as compared with only 37 percent of the controls (p<0.01), a finding which the authors stated "raises the question anew of the role of sunlight in the pathogenesis of this form of cutaneous malignancy."

Green (1984) analyzed interview data from 183 melanoma patients and 183 matched population controls (age + 5 years, sex, residence) in Queensland, Australia, to investigate the "relationship between cumulative hours of solar ultraviolet B (UV-B) radiation and melanoma (excluding lentigo maligna melanoma)." Total hours of sun exposure (as a surrogate for UV-B) were estimated by summation of reported occupational and recreational sun hours from 10 years of age onward. Results showed the cases to be more heavily exposed to the sun than controls: the relative risks increased from 3.2 (95% C.I., 0.9-12.4) for intermediate exposure (2,000-49,999 hours) to 5.3 (95% C.I., 0.9-30.8) for 50,000 or more hours of sun exposure when compared with less than 2,000 hours after adjustment for exact age, presence of nevi on arms, hair color, and sunburn propensity. The intermediate exposure category was, however, extremely broad, and it is not known how this may have affected the results or how many cases and controls were in the highest group. Eliminating exposures before 10 years of age could also have affected the results if, in fact, early sun exposures are important to the development of melanoma (see Chapter 8). Further analyses using actinic skin damage (keratoses or other skin cancers) as indicators of heavy lifetime exposure to solar UV radiation showed that the CMM patients had significantly more actinic lesions on their faces in comparison with controls (p<0.0001), resulting in an increased CMM relative risk of 2.8 (95% C.I. 1.1-7.2) after adjustment for exact age and presence of nevi on the arms. Socioeconomic factors were not controlled for and may have biased study findings.

Holman and Armstrong (1984a) analyzed data on cumulative sun exposure at residence from 511 melanoma cases and 511 matched (age, sex, residence) controls in Western Australia during 1980 and 1981. The measure of cumulative sun exposure was based on location and duration at each residence and mean annual hours of bright sunshine at each location, resulting in an estimate for lifetime exposure at home rather than an actual estimate of time spent in the sun. Analysis showed a significantly decreased odds ratio for migrants to Australia relative to native Australians; therefore, most analyses were restricted to native-born Australians. Results (Table 9-l) show significant positive trends for all CMM (p=0.003) and for SSM (p=0.020). A strong positive gradient with increasing sun exposure was seen for HMFM with an odds ratio of 3.78 for the highest exposure group; however, the p-value for trend (0.101) failed to reach statistical significance, probably due to the small number of pairs with HMFM in the analysis.

Data from this study on sun exposure were also examined by age for high levels (>2,800 mean annual hours of bright sunlight) of exposure during any age period (0-9, 10-24, 25-39, >40 years). The greatest risks for SSM were observed for high levels of sunlight in the 10-24 year age group (OR = 11.31, 95% C.I. 1.40-91.11) and in the 25-39 year age groups (OR = 3.40, 1.41-8.20). Elevated risks were seen for HMFM in each of the age groups but were not significant, probably due to small numbers.

While the measure of sun exposure in these analyses was basically ecological in nature, i.e., annual hours of bright sunlight at residence, an analysis of actinic skin damage by cutaneous microtopography showed an increasing risk for all CMMs with worsening actinic skin damage (Table 9-2). Analysis by histogenetic type showed significantly increased risks with increasing grade of actinic damage for both HMFM and SSM. History of non-melanotic skin cancer also resulted in an increased risk of melanoma, as shown in Table 9-3. The increased risk of melanoma with history of non-melanoma skin cancer remained even after control for pigmentary factors (OR = 2.87, 95% C.I. 1.64-5.04, p=0.0002). The finding of increased CMM risk with increasing actinic skin damage and with previous non-melanoma skin cancer was seen to support an association between cutaneous melanoma and sun exposure, with the strongest associations for SSM and HMFM (Holman and Armstrong 1984b).

In contrast with these results, a more recent analysis of total outdoor exposure from the same study population (Holman et al. 1986) showed that, with the exception of HMFM, all histologic types of melanoma appear to be inversely associated with total outdoor exposure (estimated by mean weekly total occupational and recreational outdoor sun exposure averaged over a working life) after control pigmentation factors. HMFM showed slightly elevated risks in the two highest exposure categories (OR = 1.40 for 16-22 hours/week; OR = 1.32 for >23 hours/week) but neither odds ratio was statistically significant, nor was there a significant trend. The inverse associations for the remaining histogenetic types (SSM, UCM, and NM) were also not significantly different from the baseline exposure group (0-10 hours/week). Analysis of the recreational sun exposure variable in this study (Holman et al. 1986) is discussed in Chapter 8 as a measure of intermittent sun exposure.

A case-control study of CMM in Western Canada (Elwood et al. 1985) examined histories of sun exposure from occupational, recreational, and vacation activities for 595 melanoma patients and 595 matched population controls (matched on age, sex, and province of residence). A significant increase in risk with increasing sun exposure from recreational and vacation activities was found even after adjusting for hair color, skin color, history of freckles, and ethnic origin (p<0.01). For occupational exposure, no trend was observed, and the only elevated risk was in the mild exposure group (approximately 8 hours per week) (RR = 1.8, 95% C.I. 1.2, 2.5). Analysis of sun exposure from all sources combined showed some elevated risks in the higher groups when compared with the lowest, but none were statistically significant, nor was there a significant trend of increase.

FINDINGS

Results of case-control studies of CMM and total sun exposure seem to vary by the measure used to estimate the exposure, and may be affected by adjustment for pigmentation factors such as hair and skin color, propensity to sunburn, and ethnic origin; adjustment for these factors tends to lower the risk estimates. Two early studies showed significantly higher proportions of melanoma cases than controls with high sun exposure, although pigmentary factors were not considered in the analyses.

Findings based on the information from the three most recent case-control studies are presented below:

9.1 A study from Western Australia which controlled for the potentially confounding effects of pigmentary factors found significantly elevated odds ratios for total CMM, SSM, and HMFM associated with increased annual hours of bright sunlight at residence, increasing actinic skin damage, and previous non-melanoma skin cancer. The same study found no increased risk for CMM or any histogenetic type of CMM with increasing total outdoor exposure in summer, as measured by mean weekly total occupational or recreational sun exposure averaged over working life.

9.2 In Queensland, Australia, elevated CMM risks were associated with increasing estimated total hours of sun exposure after 10 years of age, while controlling for exact age, presence of nevi on arms, hair color, and sunburn propensity. The confidence intervals for intermediate and higher levels of exposure included unity.

9.3 In Western Canada, an analysis of total sun exposure showed some increased risks in higher exposure groups compared with the lowest exposure group, but none were statistically significant nor was there a significant trend of increasing risk.

9.4 Studies which have evaluated the association of CMM with a measure of delivered dose of UVR (presumably modified by an individual's susceptibility to solar radiation) have shown an increased CMM risk associated with increased sun damage to the skin, even when a consistent association with cumulative exposure (as assessed by questionnaire) was not found.

REFERENCES

Elwood, J.M., Gallagher, R.P., Hill, G.B., and Pearson, J.C.G. Cutaneous melanoma in relation to intermittent and constant sun exposure - The Western Canada melanoma study. Int J Cancer 35:427-433 (1985).

Gellin, G.A., Kopf, A.W., and Garfinkel, L. Malignant melanoma: A controlled study of possibly associated factors. Arch Derm 99:43-48 (1969).

Green, A. Sun exposure and the risk of melanoma. Aust J Dermatol 25(3):99-102 (1984).

Holman, C.D.J., and Armstrong, B.K. Cutaneous malignant melanoma and indicators of total accumulated exposure to the sun: An analysis separating histogenetic types. JNCI 73:75-82 (1984a).

Holman, C.D.J., and Armstrong, B.K. Pigmentary traits, ethnic origin, benign nevi, and family history as risk factors for cutaneous malignant melanoma. JNCI 72:257-266 (1984b).

Holman, C.D.J., Armstrong, B.K., and Heenan, P.J. Relationship of cutaneous malignant melanoma to individual sunlight-exposure habits. JNCI 76:403-414 (1986).

Lancaster, H.O., and Nelson, J. Sunlight as a cause of melanoma: A clinical survey. Med J Aust. April 6:452-456 (1957).