Dong Hang

Worldwide Prevalence of Human Papillomavirus and Relative Risk of Prostate Cancer: A Meta-analysis.

Despite the increasing number of studies conducted recently to evaluate the association between HPV infections and the risk of prostate cancer, the results remain inconclusive. Furthermore, the prevalence and distribution of overall and individual HPV types worldwide in prostate cancer has not been reported until now. Therefore, we estimated the prevalence of HPV in prostate cancer by pooling data of 46 studies with 4919 prostate cancer cases, taking into account the heterogeneity of major related parameters, including study region, specimen type, HPV DNA source, detection method, publication calendar period and Gleason score. Moreover, we tested the association of HPV infections with prostate cancer risks by a meta-analysis of 26 tissue-based case-control studies. We found that the prevalence of HPV infection was 18.93% (95% CI = 17.84–20.05%) in prostate cancer cases, and most of which were high-risk HPV types (17.73%, 95% CI = 16.52–18.99%). The prevalence varied by region, PCR primers used, publication calendar period and Gleason score. Our study also showed a significantly increased risk of prostate cancer with the positivity of overall HPV detected in prostate tissues (OR = 1.79, 95% CI = 1.29–2.49) and revealed the geographic variation of association strength (P < 0.001). In conclusion, HPV infections may contribute to the risk of prostate cancer.

Expression Quantitative Trait Loci for CARD8 Contributes to Risk of Two Infection-Related Cancers—Hepatocellular Carcinoma and Cervical Cancer

Caspase recruitment domain family, member 8 (CARD8) can coordinate innate and adaptive immune responses and sensitize cells to apoptosis, which may participate in tumorigenesis of virus-induced hepatocellular carcinoma (HCC) and cervical cancer. By bioinformatics analyses, we identified several single nucleotide polymorphisms (SNPs) within a new identified long non-coding RNA (lncRNA) as expression quantitative trait loci (eQTLs) for CARD8. In this study, we therefore hypothesized that CARD8 eQTLs SNPs within lncRNA may influence the risk of HCC and cervical cancer. We performed two independent case-control studies of 1,300 cases with HBV-positive HCC and 1,344 normal controls, together with 1,486 cervical cancer patients and 1,536 control subjects to test the association between eQTLs SNP (rs7248320) for CARD8 and the risk of HCC and cervical cancer. The variant genotype of rs7248320 was significantly associated with increased risk of HCC and cervical cancer [GG vs. AA/GA: adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.03–1.61, P = 0.028 for HCC; adjusted OR = 1.34, 95% CI = 1.09–1.66, P = 0.006 for cervical cancer]. Moreover, the effect of rs7248320 on cervical cancer risk was more prominent in premenopausal women. Further interactive analysis detected a significantly multiplicative interaction between rs7248320 and menopausal status on cervical cancer risk (P = 0.018). These findings suggest that CARD8 eQTLs SNP may serve as a susceptibility marker for virus-related HCC and cervical cancer.

Low-frequency nonsynonymous variants in FKBPL and ARPC1B genes are associated with breast cancer risk in Chinese women.

Genome‐wide association studies have reported more than 100 independent common loci associated with breast cancer risk. The contribution of low‐frequency or rare variants to breast cancer susceptibility has not been well explored. Thus, we applied exome chip to genotype >200 000 low‐frequency and rare variants in 1064 breast cancer cases and 1125 cancer‐free controls and subsequently validated promising associations in another 1040 breast cancer cases and 1240 controls. We identified two low‐frequency nonsynonymous variants at FKBPL (rs200847762, OR = 0.34, 95% CI = 0.20–0.57, P = 4.31 × 10−5) and ARPC1B (rs1045012, OR = 0.56, 95% CI = 0.43–0.74, P = 4.30 × 10−5) associated with breast cancer risk. In stratification analyses, we found that the protective effect of rs200847762 was stronger in ER‐positive breast cancer (OR = 0.18, 95% CI = 0.06–0.42) than that in ER‐negative one (OR = 0.59, 95% CI = 0.31–1.05). Our findings indicate that low‐frequency variants may also contribute to breast cancer susceptibility and genetic variants in 6p21.33 and 7q22.1 are important in breast carcinogenesis.

A novel plasma circular RNA circFARSA is a potential biomarker for non-small cell lung cancer.

Emerging evidence indicates that circular RNAs (circRNAs) are implicated in cancer development. This study aimed to evaluate whether circulating circRNAs may serve as novel biomarkers for non‐small cell lung cancer (NSCLC). We used RNA sequencing (RNA‐seq) and quantitative real‐time PCR to explore cancer‐related circRNAs. Bioinformatics and functional analyses were performed to reveal biological effects of circRNAs on lung cancer cells. A total of 5471 distinct circRNAs were identified by total RNA‐seq, in which 185 were differentially expressed between cancerous and adjacent normal tissues. A circRNA derived from exon 5–7 of the FARSA gene, termed circFARSA, was observed to increase in cancerous tissues (P = 0.016), and was more abundant in patients’ plasma than controls (P < 0.001). Overexpression of circFARSA in A549 cell line significantly promoted cell migration and invasion. In silico analysis suggested that circFARSA might sponge miR‐330‐5p and miR‐326, thereby relieving their inhibitory effects on oncogene fatty acid synthase. Summarily, this study revealed circRNA profile of NSCLC for the first time and provided the evidence of plasma circFARSA as a potential noninvasive biomarker for this malignancy.

Genetic variants within the cancer susceptibility region 8q24 and ovarian cancer risk in Han Chinese women

Accumulating evidence suggests that genetic variants at chromosome 8q24 confer susceptibility to various types of cancer. This case-control study was designed to explore the relationship between genetic variants at 8q24 and ovarian cancer risk in Han Chinese women. Two variants (rs13281615 A > G and rs6983267 T > G) were genotyped in 377 ovarian cancer cases and 1034 cancer-free controls using TaqMan allelic discrimination assay. Logistic regression analysis revealed that the G allele of rs6983267 was significantly associated with increased risk of ovarian cancer (additive model: adjusted OR = 1.21, 95% CI = 1.01–1.43, P = 0.048; recessive model: adjusted OR = 1.51, 95% CI = 1.06–2.15, P = 0.023). However, no significant association was observed between rs13281615 and ovarian cancer. In stratified analysis, the risk effect of rs6983267 variant remained significant in premenopausal women (additive model: adjusted OR = 1.62, 95% CI = 1.18–2.23, P = 0.003). Summarily, this study suggested that 8q24 rs6983267 may contribute to the susceptibility of ovarian cancer in premenopausal Han Chinese women, supporting the pleiotropy of 8q24 in carcinogenesis.

KIT polymorphisms were associated with the risk for head and neck squamous carcinoma in Chinese population.

KITLG/KIT pathway plays a vital role in multiple types of human cancer including head and neck squamous cell carcinoma (HNSCC). Genetic variations in KITLG and KIT may affect the expression or function of these genes, thereby modifying cancer risk. In this study, we evaluated the association of KITLG and KIT polymorphisms with HNSCC risk among Chinese population. Twenty‐two tagging SNPs in KITLG and KIT genes were genotyped in a case‐control study with 576 HNSCC patients and 1552 healthy controls. Logistic regression analyses revealed that an upstream SNP rs6554198 [additive model: adjusted odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.74–0.97, P = 0.019] and two intron SNPs rs2237025 (additive model: adjusted OR = 0.82, 95%CI = 0.70–0.95, P = 0.007), and rs17084687 (additive model: adjusted OR = 0.85, 95%CI = 0.73–0.99, P = 0.042) of KIT were significantly associated with the decreased risk of HNSCC. Combined analysis of the three SNPs showed that subjects carrying the protective alleles had decreased risk of HNSCC in a dose‐response manner (Ptrend = 0.001). Furthermore, interaction analyses revealed a significant multiplicative interaction between rs17084687 and drinking on HNSCC risk (P = 0.012). Luciferase activity assay indicated that the allele A of potentially functional rs6554198 led to significantly lower transcription activity of KIT compared to the risk allele G. Summarily, our findings suggested that SNPs in KIT gene may play a role in genetic susceptibility to HNSCC, which may improve our understanding of the pathogenic mechanisms of this disease.

Evaluation of genetic variants in autophagy pathway genes as prognostic biomarkers for breast cancer

Autophagy-related genes (ATGs) play a critical role in the development of various diseases including cancer. However, the role of ATGs in breast cancer survival remains unclear. This study aims to investigate whether genetic variants in core ATGs are correlated with the prognosis of breast cancer. A total of 14 potentially functional variants in core ATGs were genotyped in 790 breast cancer patients. The association of each variant with breast cancer-specific survival was evaluated by log-rank test and Cox regression model. In silico analysis was also performed to evaluate the potential function of selected variants. We found that one variant in ATG7 rs8154 (A>G) was significantly associated with breast cancer-specific survival after adjusted for age and clinical stage (HR=1.61, 95% CI: 1.12-2.31, P=0.010). Stratified analysis showed that the prognostic role of rs8154 was significant in subgroups of elder age, elder menarche age, and postmenopausal status (all P<0.001). Interaction effects were also detected between rs8154 and these grouping variables. In silico analysis revealed that rs8154 was annotated to be expression quantitative trait loci (eQTL) and methylation quantitative trait loci (meQTL) based on Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets (both P<0.05). In addition, upregulated expression of ATG7 in breast cancer tissues was observed and is significantly associated with poorer overall survival (log-rank P=0.015), poorer relapse free survival (log-rank P=0.017), and poorer distant metastasis free survival (log-rank P=0.034) in different datasets. Summarily, ATG7 variant rs8154 represents a novel prognostic marker for breast cancer patients, which may shed light on clinical risk stratification and therapeutic decision making.

Hepatitis B virus infection and risk of non-alcoholic fatty liver disease: A population-based cohort study

Although non‐alcoholic fatty liver disease (NAFLD) has been studied extensively, the potential risk factors for NAFLD among chronic hepatitis B (CHB) patients have not been fully known.

Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance and seroconversion in hepatitis B e antigen-negative chronic infection patients: A population-based prospective cohort

Seroclearance of hepatitis B surface antigen (HBsAg) has been widely studied; however, seroconversion of HBsAg and characteristics of viral load among hepatitis B e antigen (HBeAg)‐negative chronic infection patients after HBsAg lost is not clear. We performed a large‐scale study in a HBeAg‐negative chronic infection cohort to evaluate spontaneous HBsAg seroclearance incidence from October 2012 to April 2017 in Jiangsu province, China. We also elucidated the characteristics of HBsAg seroconversion and hepatitis B virus (HBV) DNA detectability among patients who cleared HBsAg. A total of 2997 HBeAg‐negative chronic infection patients (mean age 52.3 ± 12.9 years at baseline) were included. With 10 519 person‐years of follow‐up, 348 patients successfully spontaneously cleared HBsAg, with an incidence rate of 3.31 per 100 person‐years. Patients with HBV DNA detectable ~1999 IU/mL at baseline had a lower probability of HBsAg seroclearance relative to those with undetectable HBV DNA, with a hazard ratio of 0.31 (95% CI = 0.23, 0.41). HBsAg seroconversion occurred in 37.3% of those patients who cleared HBsAg. The geometric mean of anti‐HBs among those with HBsAg conversion was 79.4 mIU/mL. Female had a higher HBsAg seroconversion rate (P = 0.011). Among those with HBsAg seroclearance, 11.2% still had HBV DNA levels of higher than 100 IU/mL. Patients with higher HBV DNA at baseline had a higher risk of detectable HBV DNA levels even after HBsAg seroclearance (P < 0.001). This study reveals HBsAg seroconversion rates and HBV DNA undetectability epidemiological characteristics of patients with HBsAg seroclearance and suggests that monitoring HBV DNA is needed when managing HBeAg‐negative chronic patients, even after clearing HBsAg.

Genetic variants within 17q12 are associated with the risk of cervical cancer in the Han Chinese population

Chromosome 4q12 and 17q12 have been identified as two regions associated with susceptibility to cervical cancer in a genome-wide association study. To identify potential causal variants within these two regions, we conducted a case-control study including 1486 patients with cervical cancer and 1536 age-matched (±5 years) healthy controls. Based on RegulomeDB database, 12 potentially functional variants were selected and then genotyped by using Sequenom MassARRAY. Univariate and multivariate logistic regression models were used to evaluate the associations. We found that the G allele of rs8076131 and the A allele of rs12150079 in 17q12 region were significantly associated with increased risk of cervical cancer (adjusted OR = 1.15, 95% CI = 1.02-1.30, P = 0.02 for rs8076131; adjusted OR = 1.19, 95% CI = 1.03-1.36, P = 0.02 for rs12150079). Individuals with 3-4 risk alleles of these two variants had 24% higher odds of cervical cancer than those without the risk alleles (OR = 1.24, 95% CI = 1.07-1.44, P < 0.01). The stratified analysis showed that the associations of rs8076131 and rs12150079 with cervical cancer risk were statistically significant in subgroups of older menarche age (>16 years), more parities (≥2), nonsmokers, and having no family cancer history, but the test results for subgroup heterogeneity were not significant. The current study provides the evidence that rs8076131 and rs12150079 in 17q12 region may contribute to cervical cancer susceptibility in the Han Chinese population.