Childhood obesity not linked to adult skin cancer risk, study says

By Dr. Priyom Bose, Ph.D.Reviewed by Benedette Cuffari, M.Sc.Apr 7 2024

A recent Scientific Reports study investigates whether genetically predicted childhood adiposity influences the risk of developing skin cancer in adulthood.

Study: Genetic predisposition to childhood obesity does not influence the risk of developing skin cancer in adulthood. Image Credit: Gorodenkoff / Shutterstock.com

Background

Several studies have reported that childhood obesity increases the risk of several types of cancers in adulthood. Although a causal link between body mass index (BMI) and melanoma has been established, no studies have evaluated whether childhood obesity influences the risk of developing basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC) in adulthood.

Several mechanisms have been proposed to contribute to the potential causal link between BMI and melanoma. For example, some studies have suggested that obesity increases the risk of melanoma due to greater body surface area (BSA) that subsequently increases the number of target cells at risk. This hypothesis has been supported by some observational studies indicating that BSA positively correlates with increased melanoma risk.

Nevertheless, other studies have hypothesized that obese people receive less sunlight exposure than their non-obese counterparts due to limited outdoor recreational activity. This reduced sunlight exposure could indirectly reduce the risk of melanoma. 

About the study

The current study utilized a Mendelian randomization (MR) approach to determine the effect of genetically predicted childhood adiposity on the development of skin cancer in adulthood. MR uses genetic variation to investigate potential relationships that may exist between exposures and outcomes documented in observational studies.

Generic variants and other relevant data associated with childhood obesity were obtained from a recently published genome-wide association study (GWAS) meta-analysis. The analysis included 61,111 children of European descent between two and ten years of age.

Importantly, these data were pooled from 40 individual studies from the original meta-analysis. The final analyses comprised 10,557 SCC cases, 36,479 BCC cases, and controls.

Study findings

Of the twenty-five genome-wide significant variants for childhood obesity, five were not associated with cSCC, BCC, or melanoma GWAS datasets. Therefore, twenty variants were eligible for the analysis, which explained 2.3% of the variance of BMI in childhood.

The calculated risk estimates did not identify any significant association between genetically predicted childhood BMI and the risk of skin cancer development. Sensitivity analyses were performed to determine any breaches of MR assumptions that resulted in null findings. However, this result was also consistent with the risk estimates obtained in the MR inverse-variance-weighted (IVW) method.

No pleiotropic variants for melanoma or cSCC were detected through the MR pleiotropy residual sum and outlier (MR-PRESSO) method. Here, three outlier variants for BCC were detected. Taken together, genetically predicted childhood obesity exhibited no significant effect on the development of skin cancer, including melanoma, cSCC, or BCC later in life.

The lack of an observed association between genetically predicted childhood obesity and the risk of skin cancer development in adulthood indicates that body size is not likely to increase the risk of different types of skin cancer. Thus, the current study failed to validate whether obesity reduced the risk of melanoma due to limited outdoor activities. However, future studies could further analyze this potential association using pigmentation genes as a proxy for sun exposure.

Strengths and limitations

Key strengths of the current study include the consideration of vital confounding factors and the utilization of a large dataset to determine potential causal effects. Since the childhood GWAS meta-analysis encompassed thousands of children of European descent, population stratification could be effectively performed.

Nevertheless, the current study is associated with certain limitations, such as the inclusion of participants exclusively of European descent, which limits the generalizability of the findings to a broader ethnic population. The genetic predictors of childhood obesity could also differ based on geography and ethnicity.

Conclusions

Despite the limitations, the current study strongly indicated that genetically predicted childhood adiposity does not influence skin cancer risks.

Even if genetically predicted adiposity has an effect on risk of skin cancer, the magnitude of the effect would be very low so would likely have limited public health implications or clinical relevance.”

Future studies are needed to understand whether genetic differences may impact the risk of developing skin cancer. Although genetically predicted adiposity provides essential information, it is not a faultless proxy, as genetic predisposition interacts with lifestyle and environmental factors that might influence childhood BMI.