title: Single nucleotide polymorphisms associated with colorectal cancer susceptibility and loss of heterozygosity in a Taiwanese population.
abstract: Given the significant racial and ethnic diversity in genetic variation, we are intrigued to find out whether the single nucleotide polymorphisms (SNPs) identified in genome-wide association studies of colorectal cancer (CRC) susceptibility in East Asian populations are also relevant to the population of Taiwan. Moreover, loss of heterozygosity (LOH) may provide insight into how variants alter CRC risk and how regulatory elements control gene expression. To investigate the racial and ethnic diversity of CRC-susceptibility genetic variants and their relevance to the Taiwanese population, we genotyped 705 CRC cases and 1,802 healthy controls (Taiwan Biobank) for fifteen previously reported East Asian CRC-susceptibility SNPs and four novel genetic variants identified by whole-exome sequencing. We found that rs10795668 in FLJ3802842 and rs4631962 in CCND2 were significantly associated with CRC risk in the Taiwanese population. The previously unreported rs1338565 was associated with a significant increased risk of CRC. In addition, we also genotyped tumor tissue and paired adjacent normal tissues of these 705 CRC cases to search for LOH, as well as risk-associated and protective alleles. LOH analysis revealed preferential retention of three SNPs, rs12657484, rs3802842, and rs4444235, in tumor tissues. rs4444235 has been recently reported to be a cis-acting regulator of BMP4 gene; in this study, the C allele was preferentially retained in tumor tissues (p = 0.0023). rs4631962 and rs10795668 contribute to CRC risk in the Taiwanese and East Asian populations, and the newly identified rs1338565 was specifically associated with CRC, supporting the ethnic diversity of CRC-susceptibility SNPs. LOH analysis suggested that the three CRC risk variants, rs12657484, rs3802842, and rs4444235, exhibited somatic allele-specific imbalance and might be critical during neoplastic progression.
authors: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan; Department of Education and Research, Taipei City Hospital, Taipei, Taiwan.
authors: Chih-Yung
authors: CY
authors: Yang
authors: Department of Surgery, Taipei City Hospital, Taipei, Taiwan.
authors: Ruey-Hwa
authors: RH
authors: Lu
authors: Division of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Taiwan.
authors: Chien-Hsing
authors: CH
authors: Lin
authors: VYM Genome Research Center, National Yang-Ming University, Taipei, Taiwan.
authors: Chih-Hung
authors: CH
authors: Jen
authors: VYM Genome Research Center, National Yang-Ming University, Taipei, Taiwan.
authors: Chien-Yi
authors: CY
authors: Tung
authors: Department of Surgery, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Shung-Haur
authors: SH
authors: Yang
authors: Department of Surgery, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Jen-Kou
authors: JK
authors: Lin
authors: Department of Surgery, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Jeng-Kai
authors: JK
authors: Jiang
authors: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan; Department of Education and Research, Taipei City Hospital, Taipei, Taiwan; VYM Genome Research Center, National Yang-Ming University, Taipei, Taiwan.
authors: Chi-Hung
authors: CH
authors: Lin
mesh_terms: D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D060005:Genotyping Techniques; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan / Q000208:ethnology