Relationship between sun exposure and melanoma risk for tumours in different body sites in a large case-control study in a temperate climate

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Abstract

Aim

A melanoma case-control study was conducted to elucidate the complex relationship between sun exposure and risk.

Methods

Nine hundred and sixty population-ascertained cases, 513 population and 174 sibling controls recruited in England provided detailed sun exposure and phenotype data; a subset provided serum 25-hydroxyvitamin D2 + D3 levels.

Results

Phenotypes associated with a tendency to sunburn and reported sunburn at ⩾20 years of age were associated with increased melanoma risk (odds ratio (OR) 1.56, 95% confidence intervals (CI) 1.23–1.99). Holiday sun exposure was not associated with an increased melanoma risk although this may be in part because reported sun exposure overall was much lower in those with a sun-sensitive phenotype, particularly among controls. Head and neck melanoma was associated with less sun exposure on holidays at low latitudes (OR 0.39, 95% CI (0.23–0.68) for >13 h/year compared to <3.1). Overall the clearest relationship between reported sun exposure and risk was for average weekend sun exposure in warmer months, which was protective (OR 0.67, 95% CI 0.50–0.89 for highest versus lowest tertile of exposure). Serum vitamin D levels were strongly associated with increased weekend and holiday sun exposure.

Conclusions

Sun-sensitive phenotypes and reported sunburn were associated with an increased risk of melanoma. Although no evidence was seen of a causal relationship between holiday sun exposure and increased risk, this is consistent with the view that intense sun exposure is causal for melanoma in those prone to sunburn. A protective effect of regular weekend sun exposure was seen, particularly for limb tumours, which could be mediated by photoadaptation or higher vitamin D levels.

Introduction

Many case-control studies have established phenotypic and behavioural risk factors for melanoma in populations of European origin, summarised in meta-analyses.1, 2, 3 A pooled analysis by our group4 of 15 studies confirmed that recreational sun exposure and sunburn are strong predictors of melanoma at all latitudes, whereas measures of occupational and total sun exposure appear to predict melanoma on usually-exposed body sites only at low latitudes.4 Thus in Europe and much of North America the dominant pattern of sun exposure associated with risk in fair-skinned individuals was shown to be recreational.

The relationship between sun exposure and risk is however thought to be complex: for example some studies have suggested that occupational sun exposure might actually be protective for melanoma.2 Hypotheses developed to explain this apparent anomaly are that continuous sun exposure (not associated with severe sunburn) might be protective for melanoma either by inducing photoadaptation (increased melanisation and epidermal thickening)5 or as a result of the induction of higher levels of vitamin D. Intense sun exposure leads to both DNA damage and immunosuppression,6 which are together thought to mediate carcinogenesis, and photoadaptation is thought to reduce the DNA damage.5 There are limited data to support a role for vitamin D in melanoma prevention, although some have hypothesised such a role.7 There was no evidence in a recently published cohort study of a protective effect of reported greater vitamin D intake on melanoma risk8 for example, but there are genetic data to suggest that inherited variation in the vitamin D receptor (VDR) gene is associated with melanoma risk, recently published in meta-analyses.9

We have carried out a large case-control study using a very detailed sun exposure questionnaire10 in order to better understand the complexities of the relationship between sun exposure and melanoma risk.

Section snippets

Materials and methods

Studies were approved by the UK Multi-Centre Research Ethics Committee (MREC) and the Patient Information Advisory Group (PIAG). Population-ascertained incident melanoma cases were recruited to a case-control study in a geographically defined area of the UK (Yorkshire and the Northern Region south of the River Tyne) (67% participation rate); 960 cases (aged 18–76 years) were diagnosed in the period from September 2000 to December 2005, as described previously.9, 11 Recruitment (and therefore

Results

The recruited patients were broadly representative of the total eligible population of melanoma cases (Table 1), with a similar sex ratio.15 The differences predominantly reflect the study of upper age limit of 76 years resulting in proportionately fewer head and neck tumours.

Cases and population controls were of similar age and sex with a small excess of young cases (under 40 years) and older controls. Cases were marginally more deprived than the controls (two sample t-test, p = 0.01), as reported

Discussion

The lack of a simple cumulative relationship between melanoma risk and sun exposure has caused difficulties in interpreting and conveying the nature of risk to the public. This has further recently been compounded by concerns that low levels of vitamin D, which might result from sun avoidance designed to reduce melanoma risk, could have negative effects on health generally.17, 18

We therefore carried out a case-control study addressed to better understanding the relationship between sun exposure

Conflict of interest statement

None declared.

Acknowledgements

The collection of samples in the Melanoma Cohort Study was funded by Cancer Research UK (Project Grant C8216/A6129 and Programme awards C588/A4994 and C588/A10589) and by the NIH (R01 CA83115). Recruitment was facilitated by the UK National Cancer Research Network. Julian H. Barth and Helen P. Field from the Department of Clinical Biochemistry at Leeds Teaching Hospitals Trust carried out the measurement of serum vitamin D. Patricia Mack and Kate Gamble collected data for the studies. Paul King

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