SCIENCE@home

Genes or environment: what counts most in basal cell carcinoma?

G. Argenziano,G. Brancaccio

Published 2019 in Journal of the European Academy of Dermatology and Venereology

ABSTRACT

Basal cell carcinoma (BCC) accounts for almost the 80% of skin cancer, and actual BCC tumour burden is much greater in the population than is apparent from normal incidence rates. Several observational studies have identified associations between age, sex and anatomical site, and BCC histopathological subtypes. In particular, patients with a superficial BCC more often have their BCC on the trunk and extremities than in the head and neck region, are younger and are more often female. In this issue of the journal, Verkouteren et al. tested the reproducibility of these findings and investigated for potential new predictors for patients with a superficial first BCC (sBCC). Their results, adjusted for 11 potential confounders, confirmed the finding that sBCC is more frequently seen on trunk and extremities of younger female patients as compared to nonsuperficial BCC (nsBCC). These differences in age, sex and localization could suggest a different genetic predisposition to develop sBCC. Hence, authors compared carefully selected BCC candidate single-nucleotide polymorphisms (SNPs) between patients with a superficial first BCC (sBCC) and those with a non-superficial first BCC. Of the 19 included candidate SNPs in the multivariable regression analysis, rs12203592 looked most promising (OR: 1.83, 95% CI: 1.13–2.97, P-value 0.014). This SNP is an intron variant mapped to the interferon regulatory factor 4 (IRF4) gene, which belongs to a well-known family of transcription factors that are important in the regulation of the immune system. It is possible that certain SNPs downregulate the immune system which could lead to the formation of sBCC in relatively sun-unexposed areas earlier in life. However, the SNP rs12203592 lost its significance after adjustment for multiple testing. Thus, no significant differences in genetic make-up between sBCC and nsBCC patients were found in the study by Verkouteren et al. The fact that patients with superficial first BCC were significantly younger than non-superficial first BCC patients and developed their BCCs more often on relatively sun-unexposed sites could mean that a different pattern of ultraviolet radiation (UVR) exposure, namely intense intermittent, plays a role in the aetiology of sBCC as compared to nsBCC. However, the aetiological role of UVR in BCC is still controversial. Both high lifetime cumulative UV doses and intermittent exposure are associated with BCC development although, unlike squamous cell carcinoma, pathogenetic mechanisms need further classification. Markers of chronic photodamage such as actinic keratosis, solar elastosis and lentigines have a modest association with BCC, and studies of personal sun exposure suggest lower than expected levels of risk, with typically less than a doubling in risk with high self-reported levels of sun exposure. Moreover, there are no studies achieving statistical significance in showing that sunscreens prevent BCCs. In conclusion, given the age, sex and preferred location of sBCC and the controversial role of UVR in the development of BCC, it appears more reasonable that sBCC is linked most to genetic than environmental factors. Finding a specific genetic alteration may be a challenge, but in our estimation further investigations should follow this road.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-7 of 7 references · Page 1 of 1

CITED BY

  • No citing papers are available for this paper.

Showing 0-0 of 0 citing papers · Page 1 of 1