Correlation between the rs7101 and rs1063169 polymorphisms in the FOS noncoding region and susceptibility to and prognosis of colorectal cancer

Abstract

Background: The FOS gene is located on human chromosome 14q21–31 and encodes the nuclear oncoprotein c-Fos. This study analyzed the correlation between the FOS noncoding region rs7101 and rs1063169 polymorphisms and colorectal cancer susceptibility and prognosis. Methods: We analyzed the FOS genotypes in 432 colorectal cancer patients and 315 healthy subjects by PCR/Sanger sequencing. Survival was analyzed by Kaplan–Meier and Cox regression analysis. Western blot was used to detect the expression of c-Fos protein in cancer tissues and adjacent tissues in colorectal cancer patients with different genotypes. Results: The presence of a T allele at rs7101 and a T allele at rs1063169 in FOS carried a higher risk of colorectal cancer [adjusted odds ratio (OR) = 1.237, 95% confidence interval (95% CI) = 1.131–1.346, P ≤ .001 and adjusted OR = 1.218, 95% CI = 1.111–1.327, P ≤ .001, respectively]. c-Fos protein levels were significantly higher in variant cancer tissues than in normal mucosa tissues ( P < .05), and c-Fos proteins levels were also higher in homozygous variant cancer tissues than in heterozygous variant cancer tissues. The 3-year survival rate of patients with wild-type FOS was higher than that of patients with variant FOS ( P < .05). Conclusion: The rs7101 and rs1063169 polymorphisms in the noncoding region of FOS are associated with the risk of developing colorectal cancer and the progression of colorectal cancer, which may be because the mutation enhances the expression of c-Fos protein to promote the incidence and development of colorectal cancer.

<p>Mutational Characterization and Potential Prognostic Biomarkers of Chinese Patients with Esophageal Squamous Cell Carcinoma</p>

“…54 Interestingly, we identified associations between mutation of FOS, DOT1L, and VEGFA and metastasis-negative lymph nodes in ESCC. The mutation of FOS is reportedly associated with poor prognosis in colorectal cancer, 55 and high expression of DOT1L and VEGFA indicates poor prognosis in many cancers, such as lung cancer, gastric cancer, and clear cell renal cell carcinoma. [56][57][58][59] These reports imply that mutation of these genes is potentially associated with the Figure 6 The correlation between metastatic lymph node status and the prognosis of ESCC patients.…”

The Association between Periodontitis and Human Colorectal Cancer: Genetic and Pathogenic Linkage

“…The characterization of the currently identified leader genes, reported in Table 2 , revealed their involvement in several biological processes, such as cell signaling (i.e., CTNNB1, CBL, GRB2, PIK3CA, PIK3R1), transcriptional pathways (i.e., JUN, RELA), cell proliferation/differentiation (i.e., FOS) and immuno-inflammatory processes (i.e., IL1B, IL4, IL6, IL10; see Table 2 ) [ 22 ]. Evidence supporting the role exerted by leader genes in both CRC and periodontitis pathogenesis [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ], reported in Table 2 , suggested that the pathogenic mechanisms underlying the association between periodontitis and CRC may be mainly related to the effect of the products of the leader genes on cell cycle dysregulation and on alteration of the immuno-inflammatory response.…”

“…Leader genes acting in cell cycle regulation, such as CTNNB1, FOS, JUN, GRB2, PIK3CA, and PIK3R1, may affect homeostasis in both colonic cells and periodontal tissues, causing, if dysregulated, colonic cell proliferation and malignant transformation, on the one hand, and periodontitis development and progression, on the other, as described in Table 2 [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

“…A further literature search, using the keywords reported in Table 1, was conducted on PubMed/MEDLINE and ScienceDirect search engines (using the same key words reported in Table 1), to investigate the role of leader genes in the onset and in the progression of CRC as well as of periodontitis and to highlight their putative pathogenic mechanisms in the genetic linkage between periodontitis and CRC. [16,18,19,21,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41], were employed in the literature search and were logically combined with the boolean operators AND, OR, NOT.…”

“…Cell cycle dysregulation FOS Gene(s) transcription, cell signaling, cell proliferation and differentiation rs7101 and rs1063169 FOS single nucleotide polymorphisms are considered at higher risk of CRC onset [24] and its expression increases in CRC lesions [25]. In addition, a different member of the FOS family, named…”