Body mass index and height and risk of cutaneous melanoma: Mendelian randomization analyses

Abstract

Background Height and body mass index (BMI) have both been positively associated with melanoma risk, although findings for BMI have been less consistent than height. It remains unclear, however, whether these associations reflect causality or are due to residual confounding by environmental and lifestyle risk factors. We re-evaluated these associations using a two-sample Mendelian randomization (MR) approach. Methods We identified single nucleotide polymorphisms (SNPs) for BMI and height from separate genome-wide association study (GWAS) meta-analyses. We obtained melanoma SNPs from the most recent melanoma GWAS meta-analysis comprising 12 874 cases and 23 203 controls. We used the inverse variance-weighted estimator to derive separate causal risk estimates across all SNP instruments for BMI and height. Results Based on the combined estimate derived from 730 SNPs for BMI, we found no evidence of an association between genetically predicted BMI and melanoma [odds ratio (OR) per one standard deviation (1 SD) (4.6 kg/m2) increase in BMI 1.00, 95% confidence interval (CI): 0.91–1.11]. In contrast, we observed a positive association between genetically-predicted height (derived from a pooled estimate of 3290 SNPs) and melanoma risk [OR 1.08, 95% CI: 1.02–1.13, per 1 SD (9.27 cm) increase in height]. Sensitivity analyses using two alternative MR methods yielded similar results. Conclusions These findings provide no evidence for a causal association between higher BMI and melanoma, but support the notion that height is causally associated with melanoma risk. Mechanisms through which height influences melanoma risk remain unclear, and it remains possible that the effect could be mediated through diverse pathways including growth factors and even socioeconomic status.

Body size and composition and risk of site-specific cancers in the UK Biobank and large international consortia: A mendelian randomisation study

“…We report a positive association between genetically predicted BMI and squamous cell lung cancer risk, consistent with previous MR findings [19]. Our findings of no association between BMI and melanoma risk are consistent with findings of a recent MR investigation [67]. However, we observed an inverse association between FMI and melanoma risk, but a positive association for FFMI.…”

Association between physical activity, grip strength and sedentary behaviour with incidence of malignant melanoma: results from the UK Biobank

“…Adult attained height has been found to be a proxy for genetic, environmental, nutritional and hormonal factors, which increase the risk of malignant melanoma. 12,48 Also, previous studies showed that height is positively associated with grip strength. [49][50][51] Height is Grip strength: increment of 16/8/11.5 kg (overall/women/men).…”

Construction and validation of a prognostic risk model of angiogenesis factors in skin cutaneous melanoma

“…In general, the incidence rate of melanoma in males is higher than that in females, but it is also influenced by other factors, such as location and age [ 29 ]. Height is positively correlated with the risk for melanoma, but there is insufficient evidence for the correlation between high body mass index (BMI) and melanoma [ 30 ]. In contrast, in male patients with metastatic melanoma who received targeted or immunotherapy, those who were obese had higher progression-free survival and overall survival rates than those with a normal BMI [ 31 ].…”