Elucidating the role of 8q24 in colorectal cancer
Colorectal cancer (CRC) is a common disease, increasing in the Western world and ranking second among the most common causes of cancer-related deaths.We can distinguish between familial and sporadic forms, the latter representing the majority.
One alternative strategy to overcome p53 loss is to manipulate the p53 family members, p63 and p73, which interact with p53.It was found that deleting the ∆N isoforms of p63 and p73 could compensate for p53 loss.Further, p63 regulates Dicer and DGCR8, which are prominent effectors of micro RNAs.To date, ten loci have been associated with an increased risk of CRC.Environmental factors play a role as well as other genetic factors yet to be discovered.This observation can shed light on the mechanisms underlying reported associations between 8q24 variants and disparate chronic diseases.
Single nucleotide polymorphisms (SNPs) in the 8q24 chromosome region have been associated with prostate cancer in genome-wide association studies (1–5).
A systematic pan-cancer analysis of 6538 tumour/normal samples covering ten major cancer types identified a core metabolic signature of 44 genes that exhibit high frequency somatic copy number gains/amplifications ().
Prognostic classifiers using these genes were confirmed in independent datasets for breast and kidney cancers.
They genotyped all subjects for 5 candidate single nucleotide polymorphisms (rs672888, rs1447295, rs9642880, rs16901979, and rs6983267) that were identified in previous genome-wide scans.
Although significant associations with individual single nucleotide polymorphisms were small in magnitude, the authors observed higher increases in the risks of different types of cancer with specific haplotypes, particularly when subjects were homozygous for the haplotype: for breast cancer and homozygotes for haplotype CAGCT, hazard ratio = 3.40, 95% confidence interval: 1.24, 9.21; for prostate cancer and grouped rare haplotypes, hazard ratio = 7.43, 95% confidence interval: 3.00, 18.37; and for brain cancer and homozygotes for haplotype CGGCT, hazard ratio = 13.48, 95% confidence interval: 3.00, 59.53.
Odyssey Fellow (2014-2017) Department of Molecular & Cellular Oncology Bioinformatic analyses to understand the interplay of the p53 pathway in tumorigenesis p53 is mutated in more than 50% of human cancers and plays a critical role in tumor suppression.