Qian Hao

Associations of interleukin-6 gene polymorphisms with cancer risk: Evidence based on 49,408 cancer cases and 61,790 controls

Many molecular epidemiologic studies have shown that interleukin-6 (IL-6) polymorphisms are significantly associated with susceptibility for various cancers. However, the conclusions of these studies are inconsistent. The purpose of the present study was to explore the association between three common IL-6 loci (rs1800795, rs1800796, and rs1800797) and the risk for various cancers. We systematically searched the PubMed, Web of Science, Wanfang and China national knowledge infrastructure (CNKI) databases for relevant publications and obtained 108 eligible studies, involving 49,408 cancer patients and 61,790 cancer-free controls. Odds ratio (OR), 95% confidence interval (CI), and false positive reporting probability (FPRP) were used to evaluate cancer risk. All statistical analyses were performed using the R software meta package. We observed a non-significant association between rs1800795 and overall cancer risk, while rs1800797 was found to have a false positive association with overall risk of cancer. Subgroup analyses of rs1800797 also suggested non-significant association and rs1800795 played a protective role in liver cancer. Rs1800796 was found to be associated with overall cancer risk, particularly in Asian patients and those with prostate cancer. These findings provide evidence that IL-6 polymorphisms may affect cancer risk.

CYP17 polymorphisms are associated with decreased risk of breast cancer in Chinese Han women: a case–control study

Introduction CYP17 is the second most important enzyme in estradiol synthesis. Epidemiological studies have shown the associations between CYP17 polymorphisms and cancer risk. We conducted a case–control study to evaluate the relationship between CYP17 polymorphisms (rs743572 and rs2486758) and breast cancer (BC) risk. Patients and methods This case–control study included 560 BC patients and 583 age-matched healthy controls from Northwest China. Two polymorphisms (rs743572 and rs2486758) of CYP17 were genotyped by using Sequenom MassARRAY. ORs and 95% CIs were used to evaluate the relationship. Results Compared with the wild genotype of rs743572, we found a significantly reduced risk of BC associated with the variant genotypes (heterozygote model: OR=0.69, 95% CI=0.53–0.89; homozygote model: OR=0.68, 95% CI=0.49–0.95; dominant model: OR=0.69, 95% CI=0.54–0.87; overdominant model: OR=0.78, 95% CI=0.62–0.98; allele model: OR=0.79, 95% CI=0.66–0.93). For rs2486758 polymorphism, we did not find any difference in any of the genetic models. Further stratification analysis by clinical characteristics showed rs743572 was associated with estrogen receptor status (heterozygote model: OR=2.13, 95% CI=1.47–3.08; homozygote model: OR=3.29, 95% CI=1.94–5.58; dominant model: OR=2.39, 95% CI=1.69–3.37) and progesterone receptor status (homozygote model: OR=3.17, 95% CI=1.82–5.55), but there was no association between rs2486758 and clinical characteristics of BC. Haplotype analysis showed that Grs743572Crs2486758 haplotype was a protective factor of BC (OR=0.52, 95% CI=0.40–0.67). Survival analysis did not find that CYP17 rs743572 polymorphism was associated with triple-negative BC, either in terms of overall survival or progression-free survival. Conclusion Our results suggest that CYP17 polymorphisms may reduce the susceptibility to BC in Chinese women.

Four common polymorphisms of BRIP1 (rs2048718, rs4988344, rs4986764, and rs6504074) and cancer risk: evidence from 13,716 cancer patients and 15,590 cancer-free controls

Previous studies have showed the associations between various BRCA1-interacting protein 1 (BRIP1) polymorphisms and cancer risk. But, these results were inconsistent. This meta-analysis based on 18 studies involving 13,716 cancer patients and 15,590 cancer-free controls is aimed at to evaluate the relationship between the four common SNPs of BRIP1 (rs2048718, rs4988344, rs4986764, and rs6504074) and cancer risk. The results showed a decreased risk of rs2048718 or rs4986764 for cervical cancer rather than breast cancer in the overall population (P < 0.05). However, rs6504074 was associated with gynecologic cancer risk among overall population (P < 0.05). Further stratification analyses by ethnicity indicated that all 4 polymorphisms (rs2048718, rs4988344, rs4986764, and rs6504074) were strongly related to cancer susceptibility in Chinese people (P < 0.05). This meta-analysis showed that rs6504074 may play a decreased risk of gynecologic cancer in the overall population. Rs4988344, rs4986764, and rs6504074 were significantly related to decreasing cancer risk in Chinese population.

FABP1 Polymorphisms Contribute to Hepatocellular Carcinoma Susceptibility in Chinese Population with Liver Cirrhosis: A Case-Control Study

Purpose: Single nucleotide variations in the liver fatty acid binding protein (L-FABP, FABP1) gene lead to changes in cellular signaling pathways and lipid metabolism. FABP1 polymorphisms were associated with some liver diseases, like steatotic hepatocellular carcinoma. However, the association between FABP1 rs1545224 and rs2241883 polymorphisms and hepatitis B virus-related liver cirrhosis (LC) and hepatocellular carcinoma (HCC) has not been reported. We performed this study to explore their relationship. Methods: One thousand individuals (250 healthy controls, 250 chronic HBV (CHB), 250 LC, and 250 HCC patients) were recruited. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were applied to assess the difference in allele and genotype frequencies. Cochran-Armitage trend test was used to evaluate the cumulative effect. Significant difference would be defined when the P value was less than 0.05. Results: The distribution of rs1545224 GG, AG and AA genotypes in healthy controls or CHB carriers was not significant when compared to LC or HCC patients (P>0.05). LC patients carrying at least one A allele are more likely to develop HCC in contrast with those with G allele (P<0.05). After adjustment for confounders, meaningful results were only seen in the comparison between rs1545224 AG+AA genotype carriers and GG genotype carriers among the LC patients (P<0.05). Rs2241883 polymorphism did not influence the risk of developing LC or HCC in healthy and CHB individuals, nor did it influence the risk of HCC in LC patients (P>0.05). Conclusions: Taken together, FABP1 rs1545224 polymorphism might increase HCC risk in LC patients, indicating that FABP1 rs1545224 polymorphism may be related to the process of developing HCC in Chinese patients with LC.

Prognostic Values of LAPTM4B-35 in Human Cancer: A Meta-analysis

Background: Lysosome-associated protein transmembrane-4β-35(LAPTM4B-35) has been observed overexpressed in multiple malignant tumors. However, the prognostic value of LAPTM4B-35 remains controversial. Therefore, we conducted a meta-analysis to evaluate the prognostic value of LAPTM4B-35 in human cancers. Methods: The relevant publications were obtained by systematically searching the PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI) databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for the prognosis value of LAPTM4B-35 for cancer patient. Results: Our result suggest that LAPTM4B-35 overexpression is significantly associated with poor overall survival (OS) (HR = 2.49, 95% CI = 1.87-3.32, p < 0.001), disease-free survival (DFS) (HR = 2.43, 95% CI = 1.35-4.35, p = 0.003), and progression-free survival (PFS) (HR = 4.12, 95% CI = 2.30-7.37, p < 0.001). Moreover, subgroup analysis revealed significant association with poor OS in lung (HR = 2.05, 95% CI = 1.37-3.06, p < 0.001), gastric carcinoma (HR = 1.88, 95% CI = 1.01-3.50, p < 0.047) and ovarian cancer (HR = 4.94, 95% CI = 1.44-16.94, p = 0.011). Conclusion: LAPTM4B-35 may be a novel predictive biomarker and a potential target for treatment.

Prognostic value of flotillins (flotillin-1 and flotillin-2) in human cancers: A meta-analysis

Increasing evidence indicates that flotillins which associate with cell infiltration and metastasis are overexpressed in multiple tumors. The prognostic role of flotillins remains controversial. We conducted a comprehensive meta-analysis of published research to investigate the prognostic value of flotillins in patients with cancer. Pooled HRs (hazard ratio) with 95% CIs (confidence interval) were collected to estimate the prognostic value. Twenty-seven studies with 4803 cancer patients were finally identified. The results indicated that: (1) elevated flotillins predicted poorer OS (overall survival) (HRu202f=u202f2.17, 95% CI 1.87 to 2.52; HRu202f=u202f1.61, 95% CI 1.44 to 1.81) and DFS (disease-free survival) (HRu202f=u202f2.41, 95% CI 1.83 to 3.18; HRu202f=u202f3.01, 95% CI 2.12 to 4.27) in patients with cancer; (2) Subgroup analysis showed that the prognostic value of flotillin-1 on OS and DFS in the investigated tumors were not altered by tumor type (such as digestive system cancers, renal cell cancer, lung cancer, or others), country (China or Canada), cutoff value, detection method, analysis type or paper quality and flotillin-2 overexpression indicates poor OS in human cancers except for nasopharyngeal carcinoma. Flotillins are promising as new biomarkers to predict poor prognosis of patients with tumors. This conclusion needs more clinical studies with different types of cancer to be proven.

Prognostic values of HE4 expression in patients with cancer: a meta-analysis

Background To evaluate the prognostic impact of HE4 expression in patients with cancer. Materials and methods We searched the PubMed, Web of Science, Chinese National Knowledge Infrastructure and WangFang databases for publications concerning HE4 expression in patients with cancer. The correlation of HE4 expression level with overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) was analyzed. Results In this meta-analysis, 29 studies, with a total of 4,235 patients, were included. Our results showed that HE4 expression was significantly associated with poorer OS (hazard ratio [HR] =2.15, 95% confidence interval [CI] =1.77–2.62, P<0.001). Further subgroup analysis found that this correlation was not affected by race (White: HR =1.92, 95% CI =1.53–2.39, P<0.001; Asian: HR =2.62, 95% CI =2.06–3.35, P<0.001) or tumor types (endometrial cancer: HR =2.91, 95% CI =1.86–4.53, P<0.001; ovarian cancer: HR =1.82, 95% CI =1.50–2.22, P<0.001; lung cancer: HR =2.31, 95% CI =1.54–3.47, P<0.001). Our meta-analysis showed that HE4 overexpression was significantly associated with DFS (HR =2.50, 95% CI =1.86–3.37, P<0.001) and PFS (HR =1.27, 95% CI =1.11–1.45, P=0.001). Conclusion These results suggest that expression of HE4 was associated with a worse prognosis in patients with cancer. HE4 is a potential novel prognostic factor in patients with cancer.

The role of microRNA-608 polymorphism on the susceptibility and survival of cancer: a meta-analysis

The role of rs4919510 polymorphism in microRNA-608 (miR-608) and cancer susceptibility and prognosis remain controversial and debatable. We conducted a meta-analysis of twenty-four eligible publications on the association of rs4919510 polymorphism with cancer risk and/or prognosis. Odds ratios, hazard ratios, and 95% confidence interval were used to investigate the association between this polymorphism and susceptibility, overall survival, and recurrence-free survival of cancer. Overall, eighteen case-control studies and nine cohort studies evaluated the susceptibility and prognostic value of rs4919510 polymorphism in cancer, respectively. Pooled analysis showed that rs4919510 polymorphism was not associated with cancer risk in all five genetic models. When stratifying by different cancer sites, rs4919510 polymorphism was detected to have a significant association with a decreased risk of colorectal cancer in homozygous model (P = 0.006) and recessive model (P = 0.001), subgroup analysis also emerged a weakened correlation between rs4919510 polymorphism and an increased risk of papillary thyroid cancer in heterozygote model (P = 0.04). Furthermore, the prognosis of rs4919510 variant in cancer patients showed that rs4919510 GG genotype was significant association with poor recurrence-free survival in homozygous models (P = 0.04). The meta-analysis suggested that the microRNA-608 rs4919510 polymorphism maybe associate with a significantly decreased risk for colorectal cancer. Further investigations on larger populations are required to evaluate and confirm this relationship.