Obesity and risk of malignant melanoma: A meta-analysis of cohort and case–control studies
Introduction
The epidemiology of malignant melanoma (hereafter called melanoma) has followed a long trajectory, starting with the sunlight hypothesis in the ’50s1; the current palette of risk factors essentially encompasses exogenous parameters, among which sun exposure and its correlates represent the primary cornerstone,1, 2 as well as inherent features, such as skin-eye-hair colour, family history,3 presence of common or atypical naevi,4 immunosuppression5 or even novel genetic loci.6 The attempts envisaging a link between melanoma and oral contraceptive use have not proven fruitful.7
Obesity is a well established risk factor for several cancer types8; noticeably, it has been postulated that obesity may account for approximately 20% of all cancer cases.9 The spectrum of obesity-related cancer may span, among other types, colon,10 endometrial,11 postmenopausal breast,9 renal,8, 9 oesophageal,8 thyroid,8, 9 prostate12 and possibly some haematologic malignancies.13
Regarding melanoma, a possible association with obesity remains rather unclear at the meta-analytical level, whereas individual studies have yielded mutually conflicting results. So far, two pooling approaches have appeared in the literature. Renehan et al. performed a meta-analysis especially on prospective (cohort) studies and found elevated melanoma risk with increasing body mass index (BMI) among men.8 On the other hand, Olsen et al. pooled eight case–control studies exclusively conducted on women; their results suggested a null association between BMI or body surface area (BSA) and melanoma risk.14 To our knowledge, no effort has been undertaken till now, aiming to synthesise all published cohort and case–control studies, in order to evaluate the association between melanoma and obesity.
To this end, our aim was to comprehensively examine the association between obesity and melanoma risk, synthesising all available evidence. Two indices have been assessed as markers of obesity, according to the individual studies i.e. BMI and BSA. Separate analyses were undertaken in males and females, so as to uncover sex-specific differences, if any.
Section snippets
Search terms, eligibility and exclusion criteria
This meta-analysis was conducted in accordance with the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines.15 Following a combined computerised and manual systematic database search of medical literature, potentially informative publications were retrieved from electronic search engines (Medline, Scopus, Google Scholar, Ovid and the Cochrane Library). Reference lists were thereafter systematically searched for relevant articles.
Eligible articles included case–control and
Characteristics of eligible studies
As shown in the flow diagram (Fig. 1), a total of 31,619 abstracts were identified and screened. After exclusion of the 31,584 irrelevant abstracts, 10 articles had been performed on mutually overlapping populations. In particular, the article by Odenbro et al.23 overlapped with the article by Samanic et al.,24 while the article by Naldi et al.25 overlapped with the eligible article by Gallus et al.26; in addition, eight articles27, 28, 29, 30, 31, 32, 33, 34 were excluded as they totally
Association of BMI and risk for melanoma among males
Compared with a BMI < 25 kg/m2, the pooled effect estimate for overweight males was 1.31 (95% CI: 1.18–1.45, fixed effects, Fig. 2a); similarly, the pooled effect estimate for obese males was 1.31 (95% CI: 1.19–1.44, fixed effects, Fig. 2b). Of note, the pooled estimates were practically equal regarding overweight and obese males, pointing to the existence of an underlying plateau. The positive association for both obese and overweight males was reproducible in the subsets of case–control and cohort
Discussion
The current meta-analysis, comprising both case–control and cohort studies and using two indices of obesity, showed increased melanoma risk of the same magnitude for overweight and obese males. By contrast, regarding females, the overall meta-analysis and meta-regression analysis pointed to a null association between obesity and melanoma risk. Confounding between sunlight exposure and obesity among females seemed to be a plausible underlying factor for these apparently contradictory results.
Conflict of interest statement
None declared.
Acknowledgements
We would like to thank Dr. Evangelos Evangelou, University of Ioannina, for his kind advice at the initial stage of the analysis. We would like to express our gratitude to the following colleagues, who kindly provided us with valuable data on their studies: Dr. Diane Feskanich, Dr. Silvano Gallus, Dr. Amy E. Millen, Dr. Pär Stattin and Dr. Marco Vinceti. This research has been funded in part by the Athens University Medical School. This work was supported by Karolinska Institutet, Distinguished
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