Polygenic risk scores estimate keratinocyte cancer risk in organ transplant recipients

A polygenic risk score (PRS) helps identify organ transplant recipients (OTRs) who are at high risk of developing keratinocyte cancers (KCs), which in turn could improve screening and preventive strategies, a new study has found.

Drawing from the UK Biobank and 23andMe databases, the researchers generated PRSs in nontransplantee individuals with squamous cell carcinoma (SCC; n=13,981), basal cell carcinoma (BCC; n=33,736), and controls (n>560,000). They then tested the predictive ability of the PRS in an independent OTR cohort.

From the derivation cohort, the researchers identified 142 and 31 single-nucleotide polymorphisms (SNPs) that could potentially provide the best predictive value for BCC (BCC142) and SCC (SCC31), respectively. Subsequent case-control analyses included 630 and 642 participants for the analysis of the respective PRSs.

After adjusting for traditional risk factors, the corresponding risk scores were found to be significantly associated with BCC (odds ratio [OR], 1.60, 95 percent confidence interval [CI], 1.24–2.05; p=2.6×10^–4) and SCC (OR, 1.31, 95 percent CI, 1.03–1.65; p=0.028).

The researchers then divided patients according to PRS. ORs in the top 20 percent of BCC scores saw a 23-percent absolute risk of developing BCC. Those in the bottom 20 percent only had a risk estimate of 8.7 percent, not significantly higher than the 6.8-percent BCC prevalence among nontransplantees. OTRs in the top PRS category of BCC were more than thrice as likely to develop BCC than the bottom group (OR, 3.25, 95 percent CI, 1.44–7.31; p=4.4×10^–3).

For SCC, absolute risks were 24.6 percent and 10.9 percent in the top and bottom 20 percent of PRSs, respectively, representing a more than twofold jump in likelihood (OR, 2.11, 95 percent CI, 0.98–4.53).

“OTRs in the highest genetic risk quintile could benefit from more intense KC screening and preventive strategies than their counterparts,” the researchers said.