Abstract
The incidence of basal cell carcinoma (BCC) is higher among men than women. Susceptibility loci for BCC have been identified through genome-wide association studies, and two previous studies have found polygenic risk scores (PRS) to be significantly associated with the risk of BCC. However, to our knowledge, sex-stratified PRS analyses examining the genetic contribution to BCC risk among men and women have not been previously reported. To quantify the contribution of genetic variability on the BCC risk by sex, we derived a polygenic risk score and estimated the genetic relative risk distribution for men and women. Using 29 published single nucleotide polymorphisms, we found that the estimated relative risk of BCC increases with higher percentiles of the polygenic risk score. For men, the estimated risk of BCC is twice the average population risk at the 88th percentile, while for women, this occurs at the 99th percentile. Our findings indicate that there is a significant impact of genetic variation on the risk of developing BCC and that this impact may be greater for men than for women. Polygenic risk scores may be clinically useful tools for risk stratification, particularly in combination with other known risk factors for BCC development.
Highlights
Basal cell carcinomas (BCCs) arise in over two million Americans annually, more frequently among men than women (Asgari et al, 2015)
We identified 29 single nucleeotide polymorphisms (SNPs) at 27 loci meeting our inclusion criteria (Table 1)
A two-fold increase in relative risk has been suggested as a benchmark for clinical significance in studies of genetic risk (Roberts et al, 2012)
Summary
Basal cell carcinomas (BCCs) arise in over two million Americans annually, more frequently among men than women (Asgari et al, 2015). Multiple BCC susceptibility loci have been identified via genome-wide association studies (GWAS) (Chahal et al, 2016b; Nan et al, 2011; Rafnar et al, 2009; Stacey et al, 2015, 2014, 2011, 2008). Two studies have previously examined the associations between PRS and BCC (Fritsche et al, 2018; Stapleton et al, 2019), neither stratified by sex. Since the impact of inherited genetic variation on differential BCC risk by sex has not been established, we created a PRS using published GWAS loci to estimate the sex-specific relative risk distribution owing to known risk alleles, with the goal of identifying high-risk men and women
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