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Low rectal cancer is a subtype of colorectal cancer at a special anatomic site with distinct biological behavior. TP53 is one of the most important cancer suppressor genes, and its structural variation and abnormal expression has been revealed to be associated with multiple cancer types. However, to the best of our knowledge, the association of p53 protein expression with its gene polymorphism, biological behavior and prognosis in low rectal cancer has not been clarified. Therefore, the current study aimed to explore these associations. In the present study, 347 patients with low rectal cancer and 353 controls were enrolled. Kompetitive Allele-Specific Polymerase Chain Reaction was used to detect five polymorphic sites of the TP53 gene (rs1042522, rs12947788, rs1625895, rs2909430 and rs12951053), while immunohistochemistry was used to detect the protein expression of TP53. The associations between p53 protein expression and TP53 polymorphism, biological behavior and prognosis in low rectal cancer were systematically analyzed. In low rectal cancer, p53 protein expression was markedly higher in TP53 rs1042522 mutant carriers compared with that in other genotypes where expression was higher in poorly differentiated, III–IV phase and T3-4 phase tumors, and in III–IV phase female patients. The survival time of patients with low p53 protein expression was evidently longer in females, non-smokers and patients >60 years old. In summary, p53 protein expression was identified to be affected by TP53 rs1042522 polymorphism, and was associated with the biological behavior and prognosis of low rectal cancer. TP53 rs1042522 and the associated protein expression could be used as indicators for biological behavior and prognosis in low rectal cancer. [ABSTRACT FROM AUTHOR]

Background: Damage-specific DNA binding protein 2 (DDB2) is implicated in the recognition of DNA damage and the initiation of nucleotide excision repair process. The aim of this study was to explore the role of DDB2 in the initiation, progression, and prognosis of colorectal cancer (CRC).Methods: Totally tissues of 300 CRC and 300 adjacent, 267 colorectal adenoma (CRA) and 214 normal (NOR) were collected. The expression of DDB2 protein was detected by immunohistochemical staining.Results: DDB2 protein was highly expressed in CRC and CRA compared with NOR (P < 0.001, respectively) in the dynamic sequence of NOR → CRA → CRC; CRC tissue demonstrated increased DDB2 expression compared with non-tumor adjacent tissues (P < 0.001). DDB2 expression was higher in T1-T2 than that in T3-T4 in CRC (P = 0.023); cloddy/nested CRC demonstrated increased DDB2 expression than infiltrative CRC (P = 0.007). Survival analysis showed that high DDB2 expression was associated with favorable survival in colon cancer (adjusted HR 0.20, 95% CI 0.06-0.72, P = 0.014) and female CRC patients (adjusted HR 0.27, 95% CI 0.08-0.92, P = 0.036).Conclusion: DDB2 protein expression was associated with the initiation, progression, and prognosis of CRC, and might function as a tumor biomarker for the diagnosis and prognosis of CRC. [ABSTRACT FROM AUTHOR]

Abstract: As an indispensable factor in DNA damage recognition step of nucleotide excision repair, XPA interacts with a series of proteins to initiate repair process. The expression characteristics of XPA in colorectal cancer (CRC) and its influence on CRC prognosis remain elusive. Tissue specimens of CRC and nontumor adjacent tissues from 283 patients were collected. XPA protein expressions were detected by immunohistochemistry staining. Nonparametric test was used to investigate the difference of XPA expression between CRC and nontumor adjacent tissues, as well as the correlation between XPA expression and clinicopathological parameters of CRC. Univariate and multivariate Cox proportional hazards models were applied to estimate the relationship between XPA expression and CRC prognosis. Meanwhile, we analyzed TCGA data to investigate the relation between XPA mRNA expression and survival of CRC. XPA protein expression was significantly decreased in CRC tissues compared with nontumor adjacent tissues (P = 0.001). Subgroup analysis indicated consistently significant down‐regulation of XPA in CRC tissues in age > 60 (P = 0.026), age ≤ 60 (P = 0.008), colon cancer (P = 0.009), and rectal cancer (P = 0.015) patients and males (P = 0.004). For clinicopathological parameters, CRC patients with drinking habits revealed XPA overexpression than nondrinkers (P = 0.032). For prognosis, CRC patients with high XPA protein expression had longer overall survival (OS) (HR = 0.62, 95%CI: 0.39–0.97, P = 0.037). Stratified analysis suggested a better prognosis in relation to high XPA protein expression in patients over 60 years (adjusted HR = 0.48, P = 0.021), with rectal cancer (HR = 0.56, P = 0.037), without distant metastasis (HR = 0.58, P = 0.033), without tumor deposits (HR = 0.40, P = 0.006; adjusted HR = 0.44, P = 0.028), and with tumor diameter over 4 cm (HR = 0.49, P = 0.023). DNA repair protein XPA is significantly decreased in colorectal cancer tissues than in adjacent nontumor tissues. High expression of XPA protein showed significant relationship with better survival of CRC, especially rectal cancer. XPA might be a novel biomarker but might not be an independent factor to predict prognosis of CRC patients. [ABSTRACT FROM AUTHOR]

Background. Nucleotide excision repair (NER) plays a critical role in maintaining genome integrity. This study aimed to investigate the expression of NER genes and their associations with colorectal cancer (CRC) development. Method. Expressions of NER genes in CRC and normal tissues were analysed by ONCOMINE. The Cancer Genome Atlas (TCGA) data were downloaded to explore relationship of NER expression with clinicopathological parameters and survival of CRC. Results. ERCC1, ERCC2, ERCC5, and DDB2 were upregulated while ERCC4 was downregulated in CRC. For colon cancer, high ERCC3 expression was related to better T stage; ERCC5 expression indicated deeper T stage and distant metastasis; DDB2 expression suggested earlier TNM stage. For rectal cancer, ERCC2 expression correlated with favourable T stage; XPA expression predicted worse TNM stage. ERCC2 expression was associated with worse overall survival (OS) in colon cancer (HR=1.53, P=0.043). Colon cancer patients with high ERCC4 expression showed favorable OS in males (HR=0.54, P=0.035). High XPC expression demonstrated decreased death hazards in rectal cancer (HR=0.40, P=0.026). Conclusion. ERCC1, ERCC2, ERCC4, ERCC5, and DDB2 were differently expressed in CRC and normal tissues; ERCC2, ERCC3, ERCC5, XPA, and DDB2 correlated with clinicopathological parameters of CRC, while ERCC2, ERCC4, and XPC might predict CRC prognosis. [ABSTRACT FROM AUTHOR]

Background: Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP) associated with the risk and prognosis of gastric cancer (GC) as predicting biomarkers, and furthermore, its possible mechanisms. Methods: A two-stage case-control study was designed to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588) in 107 GC patients, 107 atrophic gastritis (AG), and matched 124 controls using PCR-RFLP. Two promising SNPs were validated in another independent 1949 samples (including 579 gastric cancer patients, 649 atrophic gastritis and 721 controls) using Sequenom MassARRAY platform and sequencing. Results: We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of gastric cancer and atrophic gastritis by 1.83-fold and 1.86-fold, respectively. For gastric cancer prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P = 0.004). We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the atrophic gastritis group (P = 0.043). Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (P<0.001). Conclusions: pri-let-7a-2 rs629367 CC genotype could increase the risks of gastric cancer as well as atrophic gastritis and was also associated with poor survival of gastric cancer, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of gastric cancer. [ABSTRACT FROM AUTHOR]

Human genomic DNA is in a dynamic balance of damage and repair. Cells employ multiple and specific repair pathways, such as nucleotide excision repair (NER), as unrepaired DNA damage has deleterious consequences and could give rise to carcinogenesis. Gene polymorphisms play a crucial role in predicting the risk and prognosis of cancer. Polymorphisms of NER-related genes could alter the ability of NER to effectively monitor and repair DNA damage, and thus may be associated with genetic susceptibility, chemotherapeutic sensitivity and prognosis of cancer. In recent years, increasing studies have focused on the association between polymorphisms of NER genes and gastric cancer, the world's fourth most common cancer and the second most common cause for cancer-related death. Here we reviewed the recent studies on the associations between polymorphisms of NER genes and gastric cancer from perspectives of genetic susceptibility, chemotherapeutic sensitivity and prognosis. [ABSTRACT FROM AUTHOR]