Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies around the world. Genetic factors play a significant role in the etiology of both familial and sporadic CRC. Family-based linkage studies and recent genome sequencing studies have identified multiple CRC susceptibility genes, such as APC, MUTYH, MLH1, MSH2, MSH6, PMS2, PTEN, STK11, GREM1, BMPR1A, SMAD4, POLE, POLD1, NTHL1, and TP53. Deleterious mutations in these genes, however, are rare and account for less than 6% of CRC cases in the general population. Since 2005, genome-wide association studies (GWAS) have emerged as a powerful tool to identify common genetic variants associated with complex traits in humans, including CRC. However, most of the GWAS for CRC are conducted in European-ancestry populations, and risk variants for CRC identified in these GWAS explain only a small fraction of the familial relative risk of CRCs, particularly in non-European descendants.
In 2010, we initiated the Asia Colorectal Cancer Consortium (ACCC) to identify new genetic risk factors for CRC. Given the differences in genetic architecture and environmental exposure between Asian and European descendants, we hypothesized that our study could identify CRC genetic risk variants more specific to the Asian population and uncover important novel genetic risk variants that might otherwise be difficult to identify in European descendants. Currently, the ACCC includes GWAS data from more than 22,500 CRC cases and 212,400 controls of East-Asian ancestry from 14 studies conducted in China, Japan, and South Korea. Over the years, we identified approximately 50 novel CRC risk loci and independent risk variants in known CRC risk loci in the ACCC. In collaboration with GWAS conducted in European-ancestry populations, we identified more than 100 additional novel risk loci. Data from ACCC have been used in other studies, including transcriptome-wide association studies to identify potential susceptibility genes for CRC. In addition, using data from the ACCC, we have established models to predict CRC risk in Asians. Research conducted in the ACCC has significantly contributed to our understanding of CRC genetics and biology, which has important implications in CRC prevention and treatment. (ACCC is supported in part by NIH grant R01 CA188214.)