GWAS Links New Variant in Long Non-Coding RNA LINC02006 with Colorectal Cancer Susceptibility

SIMPLE SUMMARY: Identifying risk factors for cancer development can allow for appropriate stratification and surveillance of individuals at risk, increasing their chances of benefiting from early disease detection; however, most of the genetic factors contributing to the risk of colorectal cancer (CRC) remain undetermined. Here, we adopted a new approach for selecting index polymorphism for further validation in combination with a genome-wide association study of pooled DNA samples for CRC susceptibility variants in the Polish population. This study, including 2013 patients and controls, uncovered five susceptibility loci not previously reported for CRC. Four of identified variants were located within genes likely involved in tumor invasiveness and metastasis, suggesting that they could be markers of poor prognosis in CRC patients. Our results provide evidence that conducting association studies on small but homogenous populations can help us discover new common risk variants specific to the studied population. ABSTRACT: Despite great efforts, most of the genetic factors contributing to the risk of colorectal cancer (CRC) remain undetermined. Including small but homogenous populations in genome-wide association studies (GWAS) can help us discover new common risk variants specific to the studied population. In this study, including 465 CRC patients and 1548 controls, a pooled DNA samples-based GWAS was conducted in search of genetic variants associated with CRC in a Polish population. Combined with a new method of selecting single-nucleotide polymorphisms (SNPs) for verification in individual DNA samples, this approach allowed the detection of five new susceptibility loci not previously reported for CRC. The discovered loci were found to explain 10% of the overall risk of developing CRC. The strongest association was observed for rs10935945 in long non-coding RNA LINC02006 (3q25.2). Three other SNPs were also located within genes (rs17575184 in NEGR1, rs11060839 in PIWIL1, rs12935896 in BCAS3), while one was intergenic (rs9927668 at 16p13.2). An expression quantitative trait locus (eQTL) bioinformatic analysis suggested that these polymorphisms may affect transcription factor binding sites. In conclusion, four of the identified variants were located within genes likely involved in tumor invasiveness and metastasis. Therefore, they could possibly be markers of poor prognosis in CRC patients.