Wen Qiong Xue

Association of the Asp312Asn and Lys751Gln polymorphisms in the XPD gene with the risk of non-Hodgkin's lymphoma: evidence from a meta-analysis.

Polymorphisms in DNA repair genes may alter DNA repair capacity and, consequently, lead to genetic instability and carcinogenesis. Several studies have investigated the association of the Asp312Asn and Lys751Gln polymorphisms in the xeroderma pigmentosum complementation group D (XPD) gene with the risk of non-Hodgkin’s lymphoma (NHL), but the conclusions have been inconsistent. Therefore, we performed this meta-analysis to more precisely estimate these relationships. A systematic literature search was performed using the PubMed, Embase, and Chinese Biomedical (CBM) databases. Ultimately, 6 studies of Asp312Asn, comprising 3,095 cases and 3,306 controls, and 7 studies of Lys751Gln, consisting of 3,249 cases and 3,676 controls, were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of each association. Overall, no association was observed between the Asp312Asn polymorphism and NHL risk (homozygous: OR = 1.11, 95% CI = 0.94-1.32; heterozygous: OR = 1.00, 95% CI = 0.89-1.11; recessive: OR = 1.12, 95% CI = 0.95-1.31; dominant: OR = 1.02, 95% CI = 0.92-1.13; and allele comparison: OR = 1.04, 95% CI = 0.96-1.12) or between the Lys751Gln polymorphism and NHL risk (homozygous: OR = 0.97, 95% CI = 0.83-1.15; heterozygous: OR = 0.96, 95% CI = 0.86-1.06; recessive: OR = 1.00, 95% CI = 0.86-1.16; dominant: OR = 0.96, 95% CI = 0.87-1.06; and allele comparison: OR = 0.98, 95% CI = 0.91-1.05). Furthermore, subgroup analyses did not reveal any association between these polymorphisms and ethnicity, the source of the controls, or the NHL subtype. These results indicated that neither the Asp312Asn nor Lys751Gln XPD polymorphism was related to NHL risk. Large and well-designed prospective studies are required to confirm this finding.

HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway.

Long non‐coding RNAs (LncRNAs) have been recently found to be pervasively transcribed in the genome and critical regulators of the epigenome. HOTAIR, as a well‐known LncRNA, has been found to play important roles in several tumors. Herein, the clinical application value and biological functions of HOTAIR were focused and explored in esophageal squamous cell carcinoma (ESCC). It was found that there was a great upregulation of HOTAIR in ESCC compared to their adjacent normal esophageal tissues. Meanwhile, patients with high HOTAIR expression have a significantly poorer prognosis than those with low expression. Moreover, HOTAIR was further validated to promote migration and invasion of ESCC cells in vitro. Then some specific molecules with great significance were investigated after HOTAIR overexpression using microarray and quantitative real time‐polymerase chain reaction (qPCR). WIF‐1 playing an important role in Wnt/β‐catenin signaling pathway was selected and further tested by immunehistochemistry. Generally, inverse correlation between HOTAIR and WIF‐1 expression was demonstrated both in ESCC cells and tissues. Mechanistically, HOTAIR directly decreased WIF‐1 expression by promoting its histone H3K27 methylation in the promoter region and then activated the Wnt/β‐catenin signaling pathway. This newly identified HOTAIR/WIF‐1 axis clarified the molecular mechanism of ESCC cell metastasis and represented a novel therapeutic target in patients with ESCC.

Quantitative Association of Tobacco Smoking With the Risk of Nasopharyngeal Carcinoma: A Comprehensive Meta-Analysis of Studies Conducted Between 1979 and 2011

Over the years, many studies have attempted to establish a link between tobacco smoking and an increased risk of nasopharyngeal carcinoma (NPC), but their results have been inconsistent. To clarify this link, we first conducted a comprehensive meta-analysis to integrate the findings of epidemiologic studies from the last half-century. The methodology used for this study followed the checklist proposed by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) Group. Pooled risk estimates were generated using a random-effects model. Twenty-eight case-control studies and 4 cohort studies involving a total of 10,274 NPC cases and 415,266 comparison subjects were included. A substantial effect of smoking on the risk of NPC was identified in this study. The results showed that ever smokers had a 60% greater risk of developing the disease than never smokers (95% confidence interval: 1.38, 1.87); this was a robust dose-dependent association. More importantly, stronger associations were observed in low-risk populations and among persons with the predominant histological type of differentiated NPC than in high-risk populations and persons with an undifferentiated type; the odds ratios were 1.76 and 2.20, respectively, versus 1.29 and 1.27. In this comprehensive meta-analysis, well-established statistical evidence was provided about the role of tobacco smoking in the etiology of NPC.

Global trends in incidence and mortality of nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a rare malignancy with an extraordinarily skewed geographic distribution worldwide. Although decreasing trends in incidence and mortality of NPC have been sporadically reported in some high-risk areas, no comprehensive description of the global trends has ever been made. We accessed incidence (1970-2007) and mortality (1970-2013) data from multiple sources, with the main ones being the Cancer Incidence in Five Continents (CI5) series and the World Health Organization (WHO) cancer mortality database. During the entire period studied, age-standardized incidence rates (ASIRs) of NPC decreased significantly in southern and eastern Asia, north America and Nordic countries with average annual percent changes (AAPCs) of -0.9% to -5.4% in males and -1.1% to -4.1% in females. Declines in age-standardized mortality rates (ASMRs) are even more remarkable and extensive, with AAPCs varying from -0.9% and -0.8% to -3.7% and -6.5% in males and females, respectively. Decreasing trends in NPC incidence are probably due to tobacco control, changes in diets and economic development. Declines in mortality rates are the results of advancements in diagnostic and radiotherapy techniques, as well as decreased incidence rates.

Association of MTHFR C677T and A1298C polymorphisms with non-Hodgkin lymphoma susceptibility: Evidence from a meta-analysis

Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism and DNA synthesis. A number of studies have examined the association of MTHFR C677T and A1298C polymorphisms with non-Hodgkin lymphoma (NHL) susceptibility; however, the conclusions were contradictory. We searched available publications assessing the polymorphisms of MTHFR and NHL susceptibility from MEDLINE, EMBASE and CBM. Genotype-based mRNA expression analysis was performed using data from 270 individuals with three different ethnicities. Ultimately, a total of 7448 cases and 11146 controls from 25 studies were included for the C677T polymorphism, 6173 cases and 9725 controls from 19 studies for the A1298C polymorphism. Pooled results indicated that neither C677T nor A1298C polymorphism was associated with NHL susceptibility. However, C677T polymorphism showed a statistically significantly increased risk for Caucasians, but a decreased risk for Asians in the subgroup analysis by ethnicity. The same variants may confer increased susceptibility to develop follicular lymphoma (FL). Moreover, A1298C polymorphism was associated with increased NHL risk for Asians. This meta-analysis indicated that C677T polymorphism was associated with altered NHL susceptibility for Caucasians, Asians and FL. Increased NHL risk was also shown for A1298C among Asians. These findings warrant validation in large and well-designed prospective studies.

Plasma microRNA profiling in nasopharyngeal carcinoma patients reveals miR-548q and miR-483-5p as potential biomarkers

MicroRNAs (miRNAs), which play a role in tumorigenesis, may also serve as diagnostic or prognostic biomarkers. However, studies on human miRNA profiles in plasma from nasopharyngeal carcinoma (NPC) patients are in their infancy. Here, we used microarrays to perform systematic profiling of human miRNAs in plasma from NPC patients. We subsequently used real-time quantitative polymerase chain reaction (Q-PCR) to validate miRNAs with aberrant expression that could serve as potential biomarkers. By comparing the plasma miRNA profiles of 31 NPC patients and 19 controls, 39 of 887 human miRNAs were found to be aberrantly expressed. Considering the fold change and P value, miR-548q and miR-483-5p were validated in 132 samples from 82 NPC patients and 50 controls. Moreover, high expression of miR-548q and miR-483-5p was further found in 3 NPC cell lines and clinical biopsy tissues from 54 NPC patients and 22 controls. Our results revealed that miR-548q and miR-483-5p are potential biomarkers of NPC. Combining the receiver operating characteristic (ROC) analyses of these 2 miRNAs, an area under the ROC curve (AUC) of 0.737 with 67.1% sensitivity and 68.0% specificity were obtained, showing the preliminary diagnostic value of plasma miRNAs. Moreover, most NPC patients with a poor outcome exhibited high expression (> median) of miR-548q (70.6%) and miR-483-5p (64.7%) in tissue samples, indicating their prognostic value. The high expression levels of miR-548q and miR-483-5p in plasma, cell lines, and clinical tissues of NPC patients indicate that their roles in NPC should be explored in the future.

Increased RIPK4 expression is associated with progression and poor prognosis in cervical squamous cell carcinoma patients

Aberrant expression of receptor interacting protein kinase 4 (RIPK4), a crucial regulatory protein of Wnt/β-catenin signaling, has recently been reported to be involved in several cancers. Here, we report the potential clinical implication and biological functions of RIPK4 in cervical squamous cell carcinoma (CSCC). One hundred and ninety-eight CSCC cases, 109 low-grade squamous intraepithelial lesions (LSILs), 141 high-grade squamous intraepithelial lesions (HSILs) and 63 chronic cervicitis were collected. The expression of RIPK4 was detected by immunohistochemistry (IHC), and its clinical value and oncogenic functions were further assessed. RIPK4 expression increased significantly with disease progression from 3.2% in chronic cervicitis, 19.3% in LSILs and 85.1% in HSILs to 94.4% in CSCCs (P < 0.001). Moreover, RIPK4 may serve as a useful biomarker to distinguish HSIL from chronic cervicitis/LSIL, which are two different clinical types for therapeutic procedures, with a high sensitivity and specificity (85.1% and 86.6%, respectively) and the performance improved when combined with p16INK4a. Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037). Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells. RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients.

Association of BRCA2 N372H polymorphism with cancer susceptibility: A comprehensive review and meta-analysis

BRCA2 gene plays an important role in homologous recombination. Polymorphic variants in this gene has been suggested to confer cancer susceptibility. Numerous studies have investigated association between BRCA2 N372H polymorphism and risk of several cancers, especially breast cancer. However, the results were inconsistent. We performed a comprehensive meta-analysis to provide a more precise assessment of the association between N372H and cancer risk, following the latest meta-analysis guidelines (PRISMA). Forty six studies involving 36299 cases and 48483 controls were included in our meta-analysis. The crude ORs and the 95% CIs were used to evaluate the strength of the association. The results indicated that the BRCA2 N372H variant was significantly associated with an increased risk of overall cancer (dominant model: OR = 1.07, 95% CI = 1.01–1.13; recessive model: OR = 1.12, 95% CI = 1.02–1.23). Moreover, stratified analyses by the cancer type and source of control observed significantly increased risk associated with BRCA2 N372H in subgroups with ovarian cancer, non-Hodgkin lymphoma and population-based controls, but not breast cancer or hospital-based controls. We also found such association among Africans. Overall, the meta-analysis suggested that BRCA2 N372H may be a cancer susceptibility polymorphism. Well-designed and large-scale studies are needed to substantiate the association between BRCA2 N372H polymorphism and cancer risk.

Association between genetic variants in the XPG gene and gastric cancer risk in a Southern Chinese population.

Xeroderma pigmentosum group G (XPG) recognizes and excises DNA damage on the 3′ side during the DNA repair process. Previous studies indicated that XPG gene polymorphisms may associate with gastric cancer susceptibility, but results were inconsistent. We evaluated the association of five potentially functional XPG polymorphisms (rs2094258 C>T, rs751402 C>T, rs2296147 T>C, rs1047768 T>C, and rs873601 G>A) with gastric cancer susceptibility in 1142 gastric cancer cases and 1173 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression models. Overall, no significant association was detected between any of selected polymorphism and gastric cancer risk. However, we found that individuals carrying 3-4 risk genotypes were at significantly higher risk of gastric cancer than those with 0-2 risk genotypes (OR=1.32, 95% CI=1.04-1.68, P=0.021). The stratification analysis revealed that the cumulative effect of risk genotypes (3-4 vs. 0-2) on gastric cancer were more prominent among subgroups older than 58 years and men. In conclusion, our results indicated that none of the selected XPG polymorphism could significantly alter gastric cancer susceptibility alone. These polymorphisms might collectively confer increased gastric cancer susceptibility. These findings would be strengthened by larger prospective multicenter studies involving different ethnic populations.

XPG rs2296147 T>C polymorphism predicted clinical outcome in colorectal cancer

Xeroderma pigmentosum group G (XPG), one of key components of nucleotide excision repair pathway (NER), is involved in excision repair of UV-induced DNA damage. Single nucleotide polymorphisms (SNPs) in the XPG gene have been reported to associate with the clinical outcome of various cancer patients. We aimed to assess the impact of four potentially functional SNPs (rs2094258 C>T, rs2296147 T>C, rs751402 G>A, and rs873601 G>A) in the XPG gene on prognosis in colorectal cancer (CRC) patients. A total of 1901 patients diagnosed with pathologically confirmed CRC were genotyped for four XPG polymorphisms. Cox proportional hazards model analysis controlled for several confounding factors was conducted to compute hazard ratios (HRs) and 95% confidence intervals (CIs). Of the four included SNPs, only rs2296147 was shown to significantly affect progression-free survival (PFS) in CRC. Patients carrying rs2296147 CT/TT genotype had a significantly shorter median 10 years PFS than those carrying CC genotype (88.5 months vs. 118.1 months), and an increased progression risk were observed with rs2296147 (HR = 1.324, 95% CI = 1.046–1.667). Moreover, none of the four SNPs were associated with overall survival. In conclusion, our study showed that XPG rs2296147 CT/TT variants conferred significant survival disadvantage in CRC patients in term of PFS. XPG rs2296147 polymorphism could be predictive of unfavorable prognosis of CRC patients.