Australian researchers have concluded that the genetic architecture of sunburn and tanning are “almost identical”, after a comprehensive review of the two processes.
The findings overturned the group’s hypothesis that the two traits may differ and provided deeper insights into how these traits can be used to inform risk prediction for skin cancer.
The burning question
While sunburn and tanning can happen simultaneously in response to ultraviolet radiation, teasing out exactly how each process contributes to the risk of skin cancer has been a challenge.
“Although biologically distinct, most studies to date have not differentiated between these outcomes, conflating their genetic risk profiles,” the research team from QIMR Berghofer wrote in Journal of Investigative Dermatology [link here].
“Many studies combine tanning and sunburn into a single survey item, making it hard to assess their distinct biological or genetic bases.”
However, previous research has suggested using separate questions about tanning and sunburn increases skin cancer prediction when compared with the Fitzpatrick scale, raising a question over whether the two traits are driven by different processes.
The study aimed to compare and contrast the genetics of tanning ability and sunburn tendency to determine whether they are distinct traits.
The analysis
Genetic data from 24,163 participants in the QSkin cohort was used for two Genome Wide Association Studies (GWAS) looking at tanning and sunburn. A multi-trait analysis also incorporated GWAS data from the UK Biobank.
The work identified 16 genomic risk loci for tanning and sunburn, eight of which overlapped. The multi-trait analysis identified 108 risk loci, 63 of which were shared between the two groups.
“Most genetic variants affected both traits, suggesting a similar underlying biological pathway,” the authors said.
“Additionally, the GREML analysis showed a strong negative genetic correlation of -0.92, suggesting largely overlapping but not identical genetic architectures.”
Overall, “we found the genetic architecture of sunburn and tanning to be almost identical, overturning our hypothesis based on epidemiologic observation that these traits may differ”, the investigators said.
Fourteen of the 16 loci identified had been allocated to either sunburn or tanning in previous GWAS analyses, but the researchers also uncovered two previously unreported SNPs: rs4671938 (in SPTBN1) and rs116980848 (in PTPRN2).
The researchers found a modest phenotypic correlation between tanning and sunburn, which differed from the strong genetic correlation.
“A possible explanation for the weaker phenotypic correlation is measurement error due to limited repeatability in self-reported phenotypes,” the authors said.
The value of a ‘single tanning question’ for risk prediction
Tanning showed stronger genetic associations than sunburn in the analysis, with heritability of 37% compared with 28% for sunburn.
Dr Nirmala Pandeya, statistician at QIMR, was one of the study’s co-authors. Source: QIMR Berghofer
“Self-reported tanning ability also had greater repeatability and was a stronger predictor of future melanoma risk, which was postulated that this might explain better predictive performance,” the authors said.
In light of this, the authors said a single question about tanning “appears to be a more effective proxy for skin response to UVR and thus skin cancer risk than sunburn, and performs better than the Fitzpatrick Scale”.
“We recommend that a single survey item for tanning is the best self-reported measure for skin response to UVR and thus skin cancer risk,” they said.
Limitations of the study included the backgrounds of the cohorts analysed, with both QSkin and the UK Biobank consisting almost entirely of participants with European ancestry.
“As a result, the findings may not be applicable to populations with different ancestral backgrounds.”