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Large Genetic Screen Identifies Eight New Variants Linked to Skin Cancer Risk

By LabMedica International staff writers
Posted on 11 Mar 2020
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Image: Squamous cell carcinoma (SCC) in situ, high magnification, demonstrating an intact basement membrane (Photo courtesy of Wikimedia Commons)
Image: Squamous cell carcinoma (SCC) in situ, high magnification, demonstrating an intact basement membrane (Photo courtesy of Wikimedia Commons)
A large genome-wide association study (GWAS) identified eight new gene loci linked to the risk of developing cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers in the United States. In contrast to melanoma, SCC usually responds to treatment and rarely spreads to other parts of the body.

Previous genome-wide association studies have identified 14 single nucleotide polymorphisms (SNPs) associated with cutaneous SCC. Investigators at Indiana University (Indianapolis, USA) have expanded this knowledge by performing the largest cutaneous SCC meta-analysis to date, incorporating six international cohorts and totaling 19,149 SCC cases and 680,049 controls.

Results of this study revealed eight novel loci associated with SCC and confirmed the 14 previously associated loci. The investigators also performed fine mapping of the causal gene variants. They found that the novel SNPs occurred within skin-specific regulatory elements and implicated loci involved in cancer development, immune regulation, and keratinocyte differentiation.

Results of the current study have increased the known SCC-related loci to 22. However, these loci account for only 8.5% of the heritable risk for squamous cell skin cancer.

“This is the largest genetic-associated study for squamous cell carcinoma of the skin,” said senior author Dr. Jiali Han, professor of epidemiology at Indiana University. “Our multidisciplinary research sheds light on new biology and the etiology of squamous cell carcinoma, confirming some important genes and also identifying genes involved in this particular cancer development. We can certainly say there is some genetic overlap between squamous cell carcinoma, basal cell carcinoma, and melanoma - the three major types of skin cancer - but we also found some genes are specific for squamous cell carcinoma.”

The SCC genome-wide association study was published in the February 10, 2020, online edition of the journal Nature Communications.

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