# A Swedish Haplotype GWAS in Familial and Sporadic Site-Specific Colorectal Cancer

## TL;DR

This study identifies genetic risk loci specific to different parts of the colon in familial and sporadic colorectal cancer cases.

## Contribution

The study uses haplotype-based GWAS to discover site-specific genetic loci in familial and sporadic colorectal cancer.

## Key findings

- 29 distinct risk loci were identified for cecal and proximal colon cancer.
- 14 loci were associated with familial cecal cancer and seven with sporadic cecal cancer.
- 18 of the 29 loci contained coding genes.

## Abstract

Genetic variants specific to anatomical subsites of colorectal cancer are known to play a crucial role in its prognosis and treatment. We undertook a haplotype-based genome-wide association study (GWAS) to identify specific genetic risk loci for three sites: cecum, right colorectum, and left colorectum. Six different haplotype GWAS were performed using familial and sporadic colorectal cancer cases with tumors at three different sites. The studies included 2358 CRC cases and 1642 healthy controls. A logistic regression model using PLINK v.1.07 software was employed, and risk loci with a p-value of 5 × 10−8 were considered statistically significant. In total, 29 distinct risk loci were identified in the analyses of familial and sporadic cases of cecal and proximal colon cancer. The results from the analyses of familial and sporadic left-sided colorectal cancer did not meet the strict criteria for significance. Among the loci that were associated with cecal cancer, 14 were familial, and seven were sporadic. Among the other right-sided colon cancer loci, six were familial, and two were sporadic. Coding genes were found at 18 of the 29 loci. Our findings of site-specific genetic risk loci support the growing evidence for divergent pathways in familial and sporadic colorectal cancer across different colorectal sites. The data support a model where the rise in proximal tumors, both familial and sporadic, is influenced by genetic risk to a higher degree than that of distal tumors. These findings are important for understanding colorectal carcinogenesis and could, after future studies, lead to new applications in cancer prevention, treatment, and prognosis.