CLL Coverage from Every Angle

Genetic Relationship Between CLL and Non-Melanoma Skin Cancer?

By: Lauren Harrison, MS
Posted: Thursday, May 13, 2021

A single pleiotropic locus, 6p25.3, may be behind the observed association between genetic susceptibility to squamous cell carcinoma and increased risk of chronic lymphocytic leukemia (CLL), according to a recent meta-analysis. In addition, genetic susceptibility for CLL appears to increase the risk of basal cell carcinoma. Sonja I Berndt, PharmD, PhD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues published these findings in the International Journal of Epidemiology.

Researchers utilized data from several previous CLL and non-melanoma skin cancer genome-wide association studies to identify single nucleotide polymorphisms (SNPs) associated with CLL or skin cancer. There were 43 SNPs identified for CLL, 35 for basal cell carcinoma, and 14 for squamous cell carcinoma.

Within the 43 genetic loci for CLL and the 49 loci for skin cancers, 8 chromosomal regions were identified that had at least 1 CLL SNP and 1 skin cancer SNP located within 1 Mb of each other. The linkage disequilibrium was weak for most of these regions, except for 3q28 and 6p25.3. The allele for squamous cell carcinoma risk was positively correlated with the CLL risk allele at the 6p25.3 location, whereas the basal cell carcinoma risk allele was negatively correlated with the CLL risk allele at 3q28. In addition, at 17p13.1, the basal cell carcinoma risk allele was associated with an increased risk of CLL (odds ratio = 1.92).

A higher CLL–polygenic risk score was associated with an increased risk of basal cell carcinoma (odds ratio = 1.13), although there seemed to be no association between basal cell carcinoma polygenic risk score and CLL risk. Thus, the authors suggest, CLL may play a role in basal cell carcinoma risk, but the opposite does not appear to be true. In contrast, higher squamous cell carcinoma polygenic risk scores were noted to increase the risk of CLL (odds ratio = 1.22), a relationship driven by the 6p25.3 locus. CLL polygenic risk score seemed to have no impact on squamous cell carcinoma risk.

Disclosure: The study authors reported no conflicts of interest.

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