Comparison of Risk Allele Frequencies for Colorectal Cancer-Associated Single Nucleotide Polymorphisms Among Different Ethnic Groups Running title: CRC Risk Allele Frequency Across Populations

Background Colorectal cancer is the second leading cause of cancer-related fatalities. Recent genome-wide association studies (GWAS) identified genetic loci implicated in colorectal cancer susceptibility. This study aimed to uncover genetic factors influencing colorectal cancer rates among different populations, particularly in East Asia where prevalence is increasing. Methods A total of 423 colorectal cancer-associated single-nucleotide polymorphisms (SNPs) in the GWAS catalog were examined. Allele frequencies of these SNPs were analyzed across various populations. Data on allele frequencies at the population level were sourced from the 1000 Genomes Project and the Korean Reference Genome Database. We used Fisher's exact test to determine if the effect allele at a specific SNP was significantly overrepresented or underrepresented. Results Allele frequencies varied across populations. East Asians and Koreans showed similar patterns, distinct from Europeans. They also displayed higher genetic risk scores, correlating with colorectal cancer incidence. Conclusions Disparities in allele frequencies of colorectal cancer -associated SNPs were identified across populations, particularly between Koreans and other ethnic groups. These distinctions may help elucidate the heightened colorectal cancer prevalence, primarily among Koreans and East Asians. Our study underscores that genetic dissimilarities can, in part, account for the variance in colorectal cancer occurrence among diverse population subgroups.