Colorectal cancer (CRC) is the third most common cancer worldwide and in Indonesia. Sporadic CRC account for more than 80% of all CRC cases. The development of sporadic colon cancer is thought to be influenced among other by acquired genetic variations. Copy number variations (CNVs), are believed to play a major role in human health and disease. CNVs can lead to altered expression of genes thereby contributing to cancer development. The aim of the present study was to search for DNA regions with CNVs as biomarkers associated to genetic susceptibility for early risk predictions of colorectal cancer.
Affymetrix SNP 5.0 platform was used in search for CNV loci in DNA from 24 paired tumor and tumor-free colon tissues. Array-detected CNVs were confirmed in 77 independent samples using Taq-Man based Real-Time PCR Method.
Whole genome CNV analysis that compared primary tumor and non-cancerous epithelium revealed gains in chromosomes 7, 8, 11 and 20 and losses in chromosomes 3, 8, 18 and 20. Significant gains were mostly found in chromosome 20 at position 20q13 with a frequency of 50% in tumor samples. Examples of genes that were associated at this cytoband were TSHZ2, and DOK5/IRS6. Verification in larger number of samples revealed that Mean Copy Number Variation from DOK5/IRS6 (ratio Â± SEM) in tumor samples was 1.72 Â± 0.084 haploid copy number, whereas in normal tissues the mean CNV was 1.36 Â± 0.058 haploid copy number. Statistical analysis using Wilcoxon test revealed that the difference of ratio of CNV between tumor and normal tissues was significant (P = 2x10−5). There was a significant association between DOK5/IRS6 CNV with the incidence of colorectal cancer (P = 4x10-4, OR = 4.33, 95%CI 1.78-10.52).
Chromosome 20q13 amplifications were detected in paired tumor and normal tissues of colorectal cancer patients in Makassar, South Sulawesi Population in Indonesia; and CNVs in gene located in this locus were associated with CRC incidence in the study population.
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All authors have declared no conflicts of interest.