Bahrami Afsane, Hassanian Seyed Mahdi, Khazaei Majid, Gharib Masoumeh, Rahmani Mahsa, Fiuji Hamid, Jazayeri Mir Hadi, Moetamani-Ahmadi Mehrdad, Ferns Gordon A, Avan Amir
Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjnad, Iran.
Department of Modern Sciences & Technologies; School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmacogenomics. 2018 Apr;19(5):463-474. doi: 10.2217/pgs-2017-0096. Epub 2018 Apr 9.
Colorectal cancer (CRC) is a major cause of cancer-related-death worldwide. Despite extensive efforts to identify valid biomarkers for the risk stratification of CRC patients, there are few of proven clinical utility. It is recognized that genetic factors play a major role in determining susceptibility to CRC. Recent genome-wide association studies have demonstrated common genetic variants in a region on chromosome 9p21 associated with an increased risk of CRC. Several genetic polymorphisms have been identified in this region that are associated with CRC. Three genes are located at this locus; CDKN2B(encoding-p15), CDKN2A (encoding-p16/p14) and 3' end of CDKN2BAS (termed-antisense-noncoding-RNA in the INK4-locus [ANRIL]). ANRIL has a post-transcriptional modulatory activity, which has been shown to perturb the expression of nearby genes. It also plays an important role in coordinating tissue remodeling through regulation of cell proliferation, apoptosis, aging, extra-cellular matrix remodeling and inflammatory response. However, the role of ANRIL is not well understood in CRC. Hypermethylation of the p14 and p16 genes is often found in some tumors, including CRC. However, further studies are necessary to explore the clinical utility of these putative markers in risk stratification, and in the assessment of prognosis. In this review, we have summarized the prognostic and therapeutic potential of the p14 and p16 genes in patients with colorectal cancer.
结直肠癌（CRC）是全球癌症相关死亡的主要原因。尽管人们为确定CRC患者风险分层的有效生物标志物付出了巨大努力，但经证实具有临床实用性的标志物却很少。人们认识到遗传因素在决定对CRC的易感性方面起主要作用。最近的全基因组关联研究已经证明，9号染色体p21区域的常见基因变异与CRC风险增加有关。在该区域已鉴定出几种与CRC相关的基因多态性。该基因座上有三个基因：CDKN2B（编码p15）、CDKN2A（编码p16/p14）和CDKN2BAS的3'端（称为INK4基因座中的反义非编码RNA [ANRIL]）。ANRIL具有转录后调节活性，已被证明会干扰附近基因的表达。它还通过调节细胞增殖、凋亡、衰老、细胞外基质重塑和炎症反应，在协调组织重塑中发挥重要作用。然而，ANRIL在CRC中的作用尚未得到充分了解。p14和p16基因的高甲基化在包括CRC在内的一些肿瘤中经常出现。然而，有必要进一步研究这些假定标志物在风险分层和预后评估中的临床实用性。在这篇综述中，我们总结了p14和p16基因在结直肠癌患者中的预后和治疗潜力。
