Genetic predisposition to childhood obesity does not influence the risk of developing skin cancer in adulthood

Abstract

The relationship between body mass index (BMI) and melanoma and other skin cancers remains unclear. The objective of this study was to employ the Mendelian randomization (MR) approach to evaluate the effects of genetically predicted childhood adiposity on the risk of developing skin cancer later in life. Two-sample MR analyses were conducted using summary data from genome-wide association study (GWAS) meta-analyses of childhood BMI, melanoma, cutaneous squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC). We used the inverse-variance-weighted (IVW) methods to obtain a pooled estimate across all genetic variants for childhood BMI. We performed multiple sensitivity analyses to evaluate the potential influence of various assumptions on our findings. We found no evidence that genetically predicted childhood BMI was associated with risks of developing melanoma, cSCC, or BCC in adulthood (OR, 95% CI: melanoma: 1.02 (0.93-1.13), cSCC 0.94 (0.79-1.11), BCC 0.97 (0.84-1.12)). Our findings do not support the conclusions from observational studies that childhood BMI is associated with increased risks of melanoma, cSCC, or BCC in adulthood. Intervening on childhood adiposity will not reduce the risk of common skin cancers later in life.

Figure 1

Two-sample Mendelian randomization analyses for the associations between childhood BMI and risk of developing melanoma, squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC). OR odds ratio, CI confidence interval, N SNPs number of single nucleotide polymorphisms, NA The MR-PRESSO method did not detect any outlier variant for SCC and melanoma.

Figure 2

Scatter plots illustrating the causal effect of childhood body mass index (BMI) on risk of melanoma, squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC). The gradients of regression lines colors correspond to the instrumental variable estimates of the effect of childhood BMI on melanoma, cSCC or BCC risk, with different MR methods compared. Error bars represent 95% confidence intervals.

Figure 3

Forest plots showing the estimate for squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), and melanoma using each SNP alone as well as the overall estimate using all the SNPs with MR Egger and IVW methods. The error bars represent the 95% confidence intervals.