Elucidating the role of 8q24 in colorectal cancer
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.
Hence, it is hypothesized that non-coding RNAs regulated by p63 and p73 can be used to therapeutically target the p53 pathway..
Further, the expression and role of p63 and p73 isoforms in human tumors is not fully deciphered.
Interestingly, this signature is strongly associated with hypoxia, with nine out of ten cancer types showing increased expression and five out of ten cancer types showing increased gain/amplification of these genes in hypoxic tumours ( ≤ 0.01).
Further validation in breast and colorectal cancer cell lines highlighted squalene epoxidase, an oxygen-requiring enzyme in cholesterol biosynthesis, as a driver of dysregulated metabolism and a key player in maintaining cell survival under hypoxia.
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.
We can distinguish between familial and sporadic forms, the latter representing the majority.
Other cancers were subsequently associated with this region, including colorectal cancer (6–10), breast cancer (11, 12), pancreatic cancer (13), bladder cancer (14–16), thyroid cancer (17), smoking-related cancers (15), chronic lymphocytic leukemia (18), testicular germ tumors (19), and gliomas (20).
Investigators have also found relations between other conditions, such as diabetes mellitus (21), age-related hearing impairment (22), schizophrenia (23, 24), bipolar disorder (25), and cleft lip and palate (26, 27) and SNPs in this region.
Although a wide range of diseases was observed to be associated with a variety of SNPs, one SNP in particular (rs6983267) was associated with multiple outcomes. Although some transcripts have been described in this region, such as , but the evidence is conflicting (29, 30).
Finally, a role for micro RNA has been suggested (31–33).
Search for elucidating the role of 8q24 in colorectal cancer:
High-penetrance mutations in a small group of genes have been identified as the causal agent of colorectal cancer (CRC) in high-risk families.