Gene Summary

Gene:AMACR; alpha-methylacyl-CoA racemase
Aliases: RM, RACE, CBAS4, P504S, AMACRD
Summary:This gene encodes a racemase. The encoded enzyme interconverts pristanoyl-CoA and C27-bile acylCoAs between their (R)- and (S)-stereoisomers. The conversion to the (S)-stereoisomers is necessary for degradation of these substrates by peroxisomal beta-oxidation. Encoded proteins from this locus localize to both mitochondria and peroxisomes. Mutations in this gene may be associated with adult-onset sensorimotor neuropathy, pigmentary retinopathy, and adrenomyeloneuropathy due to defects in bile acid synthesis. Alternatively spliced transcript variants have been described. Read-through transcription also exists between this gene and the upstream neighboring C1QTNF3 (C1q and tumor necrosis factor related protein 3) gene. [provided by RefSeq, Mar 2011]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:alpha-methylacyl-CoA racemase
Source:NCBIAccessed: 01 September, 2019


What does this gene/protein do?
Show (12)

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 01 September 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Single Nucleotide Polymorphism
  • Papillary Carcinoma
  • Prostate Cancer
  • CGH
  • Microscopy, Electron, Transmission
  • Staging
  • Cohort Studies
  • Young Adult
  • Immunohistochemistry
  • Messenger RNA
  • Prostate
  • Disease Progression
  • Adenoma, Oxyphilic
  • Androgen Receptors
  • Oncogene Fusion Proteins
  • Tumor Antigens
  • Cancer Gene Expression Regulation
  • Neoplasm Grading
  • Chromosome 5
  • Trans-Activators
  • Translocation
  • Biomarkers, Tumor
  • Prostate-Specific Antigen
  • Neoplasm Metastasis
  • Biopsy
  • Kidney Cancer
  • MUC1
  • Prostatectomy
  • Adenocarcinoma
  • Renal Cell Carcinoma
  • Case-Control Studies
  • Terminology as Topic
  • Pathology, Molecular
  • Transcriptome
  • FISH
  • Gene Expression Profiling
  • Differential Diagnosis
  • Oligonucleotide Array Sequence Analysis
  • Mucins
  • Genetic Predisposition
Tag cloud generated 01 September, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (3)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: AMACR (cancer-related)

Yang J, Liu J, Chen Y, et al.
Association of CTLA-4 tagging polymorphisms and haplotypes with hepatocellular carcinoma risk: A case-control study.
Medicine (Baltimore). 2019; 98(29):e16266 [PubMed] Related Publications
It has been proposed that cytotoxic T-lymphocyte antigen 4 (CTLA-4) may attenuate the T-cell activation threshold, thereby decreasing the antitumor response and conferring susceptibility to hepatocellular carcinoma (HCC).In the present study, we selected CTLA-4 tagging single nucleotide polymorphisms (SNPs) and explored the relationship between these polymorphisms and susceptibility to HCC. A hospital-based case-control study, comprising 584 cases with HCC and 923 controls, was performed in an eastern Chinese Han population. CTLA-4 SNPs were genotyped using a custom-by-design 48-Plex SNPscan Kit.We found that the CTLA-4 rs3087243 G>A polymorphism might be associated with increased risk of HCC (GA vs GG: adjusted odds ratio [OR], 1.38; 95% confidence interval [CI], 1.04-1.85; P = .028 and AA/GA vs GG: adjusted OR, 1.43; 95% CI, 1.08-1.89; P = .012). After using Bonferroni correction, this association remained (P = .012 for the AA/GA vs GG genetic model). In addition, the power value was 0.904 in the AA/GA versus GG genetic model. Haplotype analysis showed that CTLA4 Crs16840252Ars231775Ars3087243Trs733618, Crs16840252Grs231775Ars3087243Trs733618, and other haplotypes might increase the risk of HCC risk (P = .018, <.001, and .017, respectively). However, we found that CTLA4 Trs16840252A rs231775Grs3087243Trs733618 decreased the risk of HCC (P = .020).Our results suggest that the CTLA-4 rs3087243 G>A polymorphism increases susceptibility to HCC in an eastern Chinese Han population. CTLA-4 haplotypes may influence the development of HCC. In the future, a population-based fine-mapping study with functional assessment should be performed to further determine these potential correlations.

Elmansy D, Koyutürk M
Cross-population analysis for functional characterization of type II diabetes variants.
BMC Bioinformatics. 2019; 20(Suppl 12):320 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: As Genome-Wide Association Studies (GWAS) have been increasingly used with data from various populations, it has been observed that data from different populations reveal different sets of Single Nucleotide Polymorphisms (SNPs) that are associated with the same disease. Using Type II Diabetes (T2D) as a test case, we develop measures and methods to characterize the functional overlap of SNPs associated with the same disease across populations.
RESULTS: We introduce the notion of an Overlap Matrix as a general means of characterizing the functional overlap between different SNP sets at different genomic and functional granularities. Using SNP-to-gene mapping, functional annotation databases, and functional association networks, we assess the degree of functional overlap across nine populations from Asian and European ethnic origins. We further assess the generalizability of the method by applying it to a dataset for another complex disease - Prostate Cancer. Our results show that more overlap is captured as more functional data is incorporated as we go through the pipeline, starting from SNPs and ending at network overlap analyses. We hypothesize that these observed differences in the functional mechanisms of T2D across populations can also explain the common use of different prescription drugs in different populations. We show that this hypothesis is concordant with the literature on the functional mechanisms of prescription drugs.
CONCLUSION: Our results show that although the etiology of a complex disease can be associated with distinct processes that are affected in different populations, network-based annotations can capture more functional overlap across populations. These results support the notion that it can be useful to take ethnicity into account in making personalized treatment decisions for complex diseases.

Zhong R, Chen Q, Zhang X, et al.
Association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and lung cancer risk in Chinese people: An updated meta-analysis.
Medicine (Baltimore). 2019; 98(24):e16037 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The association between Methylenetetrahydrofolate Reductase (MTHFR) polymorphisms and lung cancer risk in Chinese people has been widely explored; however, the results remain controversial. Thus, we conducted a meta-analysis to investigate the association between MTHFR gene polymorphisms and susceptibility to lung cancer in Chinese people.
OBJECTIVE: We performed an updated meta-analysis to investigate the association between MTHFR gene polymorphisms and susceptibility to lung cancer in Chinese people.
METHODS: PubMed, EMBASE, WANFANG database, and CNKI were searched to collect eligible articles. The associations of MTHFR gene polymorphism with lung cancer risk were evaluated by calculating the pooled odds ratios (ORs) and the 95% confidence interval (CI). The dominant, recessive, heterozygous, homozygous, and allelic genetic models were used to calculate the combined ORs.
RESULTS: A total of 16 eligible studies were identified in the present meta-analysis. Evidence from the pooled results indicated a significant association between the MTHFR C677T polymorphism and lung cancer susceptibility in Chinese people under the dominant, recessive, homozygous and allelic genetic models (T vs C: OR = 1.252, 95% CI, 1.090-1.437; TT vs CC: OR = 1.741, 95% CI, 1.252-2.420. (TT + CT) vs CC: OR = 1.227, 95% CI, 1.030-1.426. TT vs (CT + CC): OR = 1.606, 95% CI, 1.207-2.137).
CONCLUSION: The present updated meta-analysis demonstrated that the MTHFR C677T polymorphism was significantly associated with susceptibility to lung cancer in Chinese people. Additional case-control studies with large sample sizes are needed to validate our findings.

Liu F, Zou Y, Wang F, et al.
Genet Test Mol Biomarkers. 2019; 23(6):409-417 [PubMed] Related Publications

Echevarria MI, Awasthi S, Cheng CH, et al.
African American Specific Gene Panel Predictive of Poor Prostate Cancer Outcome.
J Urol. 2019; 202(2):247-255 [PubMed] Related Publications
PURPOSE: Most prostate cancer in African American men lacks the ETS (E26 transforming specific) family fusion event (ETS-). We aimed to establish clinically relevant biomarkers in African American men by studying ETS dependent gene expression patterns to identified race specific genes predictive of outcomes.
MATERIALS AND METHODS: Two multicenter cohorts of a total of 1,427 men were used for the discovery and validation (635 and 792 men, respectively) of race specific predictive biomarkers. We used false discovery rate adjusted q values to identify race and ETS dependent genes which were differentially expressed in African American men who experienced biochemical recurrence within 5 years. Principal component modeling along with survival analysis was done to assess the accuracy of the gene panel in predicting recurrence.
RESULTS: We identified 3,047 genes which were differentially expressed based on ETS status. Of these genes 362 were differentially expressed in a race specific manner (false discovery rate 0.025 or less). A total of 81 genes were race specific and over expressed in African American men who experienced biochemical recurrence. The final gene panel included APOD, BCL6, EMP1, MYADM, SRGN and TIMP3. These genes were associated with 5-year biochemical recurrence (HR 1.97, 95% CI 1.27-3.06, p = 0.002) and they improved the predictive accuracy of clinicopathological variables only in African American men (60-month time dependent AUC 0.72).
CONCLUSIONS: In an effort to elucidate biological features associated with prostate cancer aggressiveness in African American men we identified ETS dependent biomarkers predicting early onset biochemical recurrence only in African American men. Thus, these ETS dependent biomarkers representing ideal candidates for biomarkers of aggressive disease in this patient population.

Long X, Li Z, Huang Y, et al.
Identification of pathogenic mutations in 6 Chinese families with multiple exostoses by whole-exome sequencing and multiplex ligation-dependent probe amplification: Case series.
Medicine (Baltimore). 2019; 98(20):e15692 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Hereditary multiple exostoses (HMEs) is an autosomal dominant skeletal disorder.
PATIENT CONCERNS: Six probands of the 6 unrelated Han Chinese families were identified as having HME. These patients had exostoses at multiple sites and significantly affected joints malformation and movement.
DIAGNOSES: Hereditary multiple exostoses.
INTERVENTIONS: To detect the genetic mechanism of HME in 6 unrelated Chinese families, whole-exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA) were used after genomic DNA was isolated from peripheral blood leucocytes. Point mutations identified by these methods were verified by Sanger sequencing after PCR amplification.
OUTCOMES: Six mutations in the EXT1 and EXT2 genes were identified, including a heterozygous deletion mutation from exon 2 to exon 8 (Family 1), a c.448C>T, p.(Gln150X) heterozygous nonsense mutation (Family 4), a c.1057-2A>T heterozygous splicing substitution (Family 5), and a c.1468dupC, p.(Leu490fs519X) (Family 6) heterozygous duplication mutation in the EXT1 gene in addition to a heterozygous deletion mutation from exon 2 to exon 3 (Family 2) and a c.1197C>G, p.(Tyr399X) heterozygous nonsense mutation (Family 3) in the EXT2 gene.
LESSONS: Overall, we identified 5 novel mutations and 1 recurrent mutation in the EXT1 and EXT2 genes in 6 Chinese families with HME. Our findings expand the mutational spectrum of the EXT1 and EXT2 genes and are useful for genetic counseling and prenatal diagnosis.

Law PJ, Timofeeva M, Fernandez-Rozadilla C, et al.
Association analyses identify 31 new risk loci for colorectal cancer susceptibility.
Nat Commun. 2019; 10(1):2154 [PubMed] Free Access to Full Article Related Publications
Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.

Xu X, Yang J, Zhou W, et al.
Genetic variations within alternative splicing associated genes are associated with breast cancer susceptibility in Chinese women.
Gene. 2019; 706:140-145 [PubMed] Related Publications
BACKGROUND: Alternative splicing regulates most of protein-coding genes by producing diverse messenger RNA transcripts; and mis-splicing events can induce aberrant protein isoforms that contribute to cancer development. It is possible that genetic variations in splicing associated genes may regulate the formation of transcripts and multiple protein isoforms by affecting the splice regulatory elements. In this study, we aimed to determine whether genetic variations in the crucial alternative-splicing genes were associated with breast cancer risk.
MATERIALS AND METHODS: A case-control study was conducted with 1064 breast cancer cases and 1073 healthy controls from China. A total of 16 tagging polymorphisms within three splicing factor-associated genes (SFRS3, ESRP1 and ESRP2) were genotyped by using Infinium BeadChip. The association between the polymorphisms and risk of breast cancer was evaluated by computing odds ratios (OR) and 95% confidence intervals (CIs).
RESULTS: The genotype distribution of rs2145048 in SFRS3 was different between cases and controls (Bonferroni corrected P = 0.022). After adjusting for age, age at menarche and menopausal status, the A allele of rs2145048 showed an inverse association with breast cancer risk in the additive model (adjusted OR = 0.81, 95% CI = 0.71-0.92, P = 0.001, Bonferroni corrected P = 0.016). In the stratification analysis, the association between rs2145048 A allele and breast cancer remained significant in subgroups of earlier menarche, older first born, premenopausal status, and ER/PR negative status.
CONCLUSIONS: This study provided the first evidence that SFRS3 rs2145048 was associated with breast cancer susceptibility in Chinese women, which might represent a biomarker to improve the identification of individuals at high risk of this malignancy.

Dai J, Gao H, Xue J, et al.
The Association Between
Genet Test Mol Biomarkers. 2019; 23(6):393-400 [PubMed] Related Publications

Pippa S, Mannironi C, Licursi V, et al.
Small Molecule Inhibitors of KDM5 Histone Demethylases Increase the Radiosensitivity of Breast Cancer Cells Overexpressing JARID1B.
Molecules. 2019; 24(9) [PubMed] Free Access to Full Article Related Publications

Yun X, Bai Y, Li Z, et al.
rs895819 in microRNA-27a increase stomach neoplasms risk in China: A meta-analysis.
Gene. 2019; 707:103-108 [PubMed] Related Publications
BACKGROUND: Across the globe, gastric cancer is a significant public health problem. This meta-analysis was conducted to investigate the association of microRNA-27a (miRNA-27a) rs895819 with gastric cancer risk.
METHODS: The search of databases updated on October 10, 2018 included Pubmed, Embase, Cochrane Library and Web of science. Odds ratio (ORs) and 95% confidence interval (CIs) were calculated to assess the risk of tumor.
RESULTS: Overall meta-analysis suggested the miRNA-27a rs895819 was not related to the gastric carcinogenesis among all model including allele contrast (G vs A, pooled OR: 1.096, 95% CI: 0.962-1.249, P = 0.196), codominant model (GG vs AA, pooled OR: 1.124, 95% CI: 0.794-1.592, P = 0.590; AG vs AA, pooled OR: 1.101, 95% CI: 0.966-1.217, P = 0.060), dominant model (AG + GG vs AA, pooled OR: 1.123, 95% CI: 0.964-1.307, P = 0.136) and recessive model (GG vs AG + AA, pooled OR: 0.927, 95% CI: 0.673-1.278, P = 0.644). Interestingly, among different ethnicity group, significant relation between rs895819 and gastric cancer was observed in co-dominant model among Chinese population (AG vs AA, pooled OR: 1.158, 95% CI: 1.038-1.291, P = 0.008) but not some regions of European population (AG vs AA, pooled OR: 0.852, 95% CI: 0.632-1.148, P = 0.179).
CONCLUSIONS: Our results find that rs895819 contributed to occurrence of gastric cancer in co-dominant model in Chinese population.

Chen S, Chen L, Tan Y, Wang J
Association between rs20417 polymorphism in cyclooxygenase-2 and gastric cancer susceptibility: Evidence from15 case-control studies.
Medicine (Baltimore). 2019; 98(18):e15468 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: Previous studies have reported an association between cyclooxygenase-2 (COX-2) polymorphism and gastric cancer (GC) susceptibility, but their results are controversial. This meta-analysis was intended to evaluate the relationship between the COX-2 rs20417 polymorphism and GC susceptibility in different ethnic groups.
METHODS: We searched PubMed, EMBASE, Web of Knowledge, and the Chinese Biomedical Database (CBM) for relevant case-control studies published up to October 6, 2018, which reported an association between the COX-2 rs20417 polymorphism and gastric cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of this association.
RESULTS: 15 papers detailing case-control studies were included in the analysis, which included a total of 2848 GC cases and 4962 healthy controls. The meta-analysis results indicated that the COX-2 rs20417 polymorphism was associated with increased GC susceptibility under allele (G vs C: OR = 1.67, 95%CI = 1.19-2.35, P = .003), heterozygous (GG vs CG: OR = 1.44, 95%CI = 1.03-2.02, P = .034), dominant (GC+CC vs GG: OR = 1.66, 95%CI = 1.18-2.34, P = .004), homozygous (GG vs CC:OR = 2.20, 95%CI = 1.07-4.54, P = .033), and recessive models (CC vs GG+CG:OR = 2.05, 95%CI = 1.09-3.85, P = .025). An analysis of ethnic subgroups revealed that the COX-2 rs20417 polymorphism was significantly associated with GC susceptibility in Asians under all 5 models (G vs C: OR = 2.22, 95%CI = 1.66-2.96, P < .001; GG vs CC: OR = 4.29, 95%CI = 1.94-9.50, P < .001; GG vs CG: OR = 1.86, 95%CI = 1.34-2.58, P < .001; CC vs GG+CG: OR = 3.73, 95%CI = 1.92-7.24, P < .001; GC+CC vs GG: OR = 2.20, 95%CI = 1.65-2.93, P < .001). Helicobacter pylori positive patients suffered a high risk of GC, compared to H pylori negative patients under the dominant model (OR = 3.09, 95%CI = 1.80-5.32, P < .001).
CONCLUSION: This meta-analysis of 15 case-control studies provides strong evidence that the COX-2 rs20417 polymorphism increases the risk of GC susceptibility in general populations, especially in Asians. Helicobacter pylori positive patients and those with the COX-2 rs20417 polymorphism had a higher risk of developing GC.

Hua RX, Zhuo Z, Zhu J, et al.
LIG3 gene polymorphisms and risk of gastric cancer in a Southern Chinese population.
Gene. 2019; 705:90-94 [PubMed] Related Publications
DNA ligase III (LIG3) has been implicated in the etiology of cancer. However, few studies have accessed the association of LIG3 single nucleotide polymorphisms (SNPs) with gastric cancer risk, especially in Chinese population. The current study was undertaken to investigate contribution of LIG3 gene polymorphisms to gastric cancer risk. We first applied TaqMan assay to genotype three LIG3 gene SNPs (rs1052536 C > T, rs3744356 C > T, rs4796030 A > C) in 1142 patients with gastric cancer and 1173 healthy controls. And then, we adopted unconditional multivariate logistic regression analysis to estimate the association between LIG3 SNP genotypes and gastric cancer risk. In all, no positive association was found between the three LIG3 SNPs and gastric cancer risk in single locus analysis or combined risk genotypes analysis. However, compared with participants with rs4796030 AA genotype, participants with the AC/CC had a decreased risk of developing tumors from cardia at an adjusted OR of 0.68 (95% CI = 0.48-0.96, P = 0.026). In addition, we found that participants harboring 2-3 risk genotypes were at a significantly increased risk of developing tumor from cardia (adjusted OR = 1.63, 95% CI = 1.16-2.28, P = 0.005). These results suggest that genetic variations in LIG3 gene may play a weak role in modifying the risk of gastric cancer. Future functional studies should be performed to elucidate the biological role of LIG3 polymorphisms in gastric cancer carcinogenesis.

Cocchiola R, Rubini E, Altieri F, et al.
STAT3 Post-Translational Modifications Drive Cellular Signaling Pathways in Prostate Cancer Cells.
Int J Mol Sci. 2019; 20(8) [PubMed] Free Access to Full Article Related Publications
STAT3 is an oncoprotein overexpressed in different types of tumors, including prostate cancer (PCa), and its activity is modulated by a variety of post-translational modifications (PTMs). Prostate cancer represents the most common cancer diagnosed in men, and each phase of tumor progression displays specific cellular conditions: inflammation is predominant in tumor's early stage, whereas oxidative stress is typical of clinically advanced PCa. The aim of this research is to assess the correspondence between the stimulus-specificity of STAT3 PTMs and definite STAT3-mediated transcriptional programs, in order to identify new suitable pharmacological targets for PCa treatment. Experiments were performed on less-aggressive LNCaP and more aggressive DU-145 cell lines, simulating inflammatory and oxidative-stress conditions. Cellular studies confirmed pY705-STAT3 as common denominator of all STAT3-mediated signaling. In addition, acK685-STAT3 was found in response to IL-6, whereas glutC328/542-STAT3 and pS727-STAT3 occurred upon tert-butyl hydroperoxyde (tBHP) treatment. Obtained results also provided evidence of an interplay between STAT3 PTMs and specific protein interactors such as P300 and APE1/Ref-1. In accordance with these outcomes, mRNA levels of STAT3-target genes seemed to follow the differing STAT3 PTMs. These results highlighted the role of STAT3 and its PTMs as drivers in the progression of PCa.

Xiang XH, Yang L, Zhang X, et al.
Seven-senescence-associated gene signature predicts overall survival for Asian patients with hepatocellular carcinoma.
World J Gastroenterol. 2019; 25(14):1715-1728 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Cellular senescence is a recognized barrier for progression of chronic liver diseases to hepatocellular carcinoma (HCC). The expression of a cluster of genes is altered in response to environmental factors during senescence. However, it is questionable whether these genes could serve as biomarkers for HCC patients.
AIM: To develop a signature of senescence-associated genes (SAGs) that predicts patients' overall survival (OS) to improve prognosis prediction of HCC.
METHODS: SAGs were identified using two senescent cell models. Univariate COX regression analysis was performed to screen the candidate genes significantly associated with OS of HCC in a discovery cohort (GSE14520) for the least absolute shrinkage and selection operator modelling. Prognostic value of this seven-gene signature was evaluated using two independent cohorts retrieved from the GEO (GSE14520) and the Cancer Genome Atlas datasets, respectively. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive accuracy of the seven-SAG signature and serum α-fetoprotein (AFP).
RESULTS: A total of 42 SAGs were screened and seven of them, including
CONCLUSION: We developed a seven-SAG signature, which could predict OS of Asian HCC patients. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.

Deng S, Ren ZJ, Jin T, et al.
Contribution of prostate stem cell antigen variation rs2294008 to the risk of bladder cancer.
Medicine (Baltimore). 2019; 98(16):e15179 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: Number of studies have been performed to evaluate the relationship between prostate stem cell antigen (PSCA) variation rs2294008 and bladder cancer risk, but the sample size was small and the results were conflicting. This meta-analysis was conducted to comprehensively evaluate the overall association.
METHODS: Pubmed, Web of science, Embase, China biology medical literature database (CBM), China National Knowledge Infrastructure (CNKI), Wan Fang and Weipu databases were searched before June 30, 2018. The strength of associations was assessed using odds ratios (ORs) and 95% confidence intervals (CIs). All of the statistical analyses were conducted using Review Manager 5.3 and Stata 14.0.
RESULTS: Ten studies involved 14,021 cases and 26,871 controls. Overall, significant association was observed between the PSCA gene variant rs2294008 polymorphism and bladder cancer (T vs C: OR = 1.16, 95%CI = 1.12-1.20; TT vs CC: OR = 1.32, 95%CI = 1.24-1.41; TT vs CT+CC: OR = 1.15, 95%CI = 1.09-1.22; TT+CT vs CC: OR = 1.27, 95%CI = 1.21-1.34). In subgroup analysis by ethnic group, a statistically significant association was observed in Asians (T vs C: OR = 1.23, 95%CI = 1.15-1.31) and Caucasians (T vs C: OR = 1.14, 95%CI = 1.10-1.18). The sensitivity analysis confirmed the reliability and stability of the meta-analysis.
CONCLUSION: Our meta-analysis supports that the PSCA gene variant rs2294008 polymorphism might contribute to individual susceptibility to bladder cancer.

Møller T, James JP, Holmstrøm K, et al.
Co-Detection of miR-21 and TNF-α mRNA in Budding Cancer Cells in Colorectal Cancer.
Int J Mol Sci. 2019; 20(8) [PubMed] Free Access to Full Article Related Publications
MicroRNA-21 (miR-21) is upregulated in many cancers including colon cancers and is a prognostic indicator of recurrence and poor prognosis. In colon cancers, miR-21 is highly expressed in stromal fibroblastic cells and more weakly in a subset of cancer cells, particularly budding cancer cells. Exploration of the expression of inflammatory markers in colon cancers revealed tumor necrosis factor alpha (TNF-α) mRNA expression at the invasive front of colon cancers. Surprisingly, a majority of the TNF-α mRNA expressing cells were found to be cancer cells and not inflammatory cells. Because miR-21 is positively involved in cell survival and TNF-α promotes necrosis, we found it interesting to analyze the presence of miR-21 in areas of TNF-α mRNA expression at the invasive front of colon cancers. For this purpose, we developed an automated procedure for the co-staining of miR-21, TNF-α mRNA and the cancer cell marker cytokeratin based on analysis of frozen colon cancer tissue samples (

Kiet NC, Khuong LT, Minh DD, et al.
Spectrum of mutations in the
Mol Vis. 2019; 25:215-221 [PubMed] Free Access to Full Article Related Publications
Purpose: Retinoblastoma (RB) is a rare childhood malignant disorder caused by the biallelic inactivation of the
Methods: Tumor RNA from 50 probands with RB, including 12 bilateral and 38 unilateral cases, was extracted. cDNA, after reverse transcription, was sequenced to identify the RNA mutation of the
Results: Forty-one different kinds of
Conclusions: Mutations in the

Wang T, Feng Y, Zhao Z, et al.
IL1RN Polymorphisms Are Associated with a Decreased Risk of Esophageal Cancer Susceptibility in a Chinese Population.
Chemotherapy. 2019; 64(1):28-35 [PubMed] Related Publications
BACKGROUND: Recent evidence suggested that IL1RN (interleukin-1 receptor antagonist) polymorphisms increased the susceptibility to cancers. The present study aimed to evaluate whether IL1RN was related to esophageal cancer susceptibility in a Northwest Han Chinese population.
METHODS: The case-control study was conducted on 384 esophageal cancer patients and 499 healthy controls. We successfully genotyped four SNPs distributed in IL1RN. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to observe the expression of IL1RN in esophageal cancer tissues and normal tissues. RegulomeDB and HaploReg v4.1 were used to calculate possible functional effects of the polymorphisms. We also used genetic models to detect any potential association between IL1RN variants and esophageal cancer risk.
RESULTS: In our study, rs3181052 was associated with a reduced risk of esophageal cancer in the codominant (odds ratio [OR] = 0.70, 95% confidence interval [CI] 0.52-0.93, p = 0.040), the dominant (OR = 0.75, 95% CI 0.57-0.99, p = 0.041), and the overdominant (OR = 0.71, 95% CI 0.54-0.93, p = 0.012) model. The rs452204 was associated with a 0.76-fold (OR = 0.76, 95% CI 0.58-0.99; p = 0.043) decreased esophageal cancer risk under the overdominant model without adjustment. We also found that rs3181052 had a negative effect on esophageal cancer under the overdominant model (OR = 0.72, 95% CI 0.53-0.97, p = 0.033) adjusted for age and gender. In stratified analyses by age >55 years, rs3181052 reduced the risk of esophageal cancer in the dominant and overdominant models. In addition, rs315919 had a remarkable influence on esophageal cancer risk in females, while the association was not significant between rs3181052 and esophageal cancer risk in males.
CONCLUSIONS: Our study provided the first evidence that IL1RN rs3181052, rs452204, and rs315919 are correlated with a decreased risk of esophageal cancer in a Northwest Han Chinese population. These findings may be useful for the development of early prognostics for esophageal cancer. However, further larger studies on different ethnic populations are warranted to verify these findings.

Zhu X, Qin M, Li C, et al.
Downregulated Expression of Chromobox Homolog 7 in Hepatocellular Carcinoma.
Genet Test Mol Biomarkers. 2019; 23(5):348-352 [PubMed] Related Publications

Liu Y, Wang M, Chen Q, et al.
A novel heterozygous large deletion of MSH6 gene in a Chinese family with Lynch syndrome.
Gene. 2019; 704:103-112 [PubMed] Related Publications
Lynch syndrome (LS) is a common cancer syndrome that is inherited in an autosomal dominant manner. Its pathogenesis is thought to be closely related to germline mutations of mismatch repair (MMR) genes such as the MLH1, MSH2, PMS2 and MSH6 genes. This study identifies a Chinese family with LS clinically diagnosed according to the Amsterdam II criteria. In these patients, immuno-histochemical staining showed negative MSH6 expressions but positive MLH1, MSH2, and PMS2 expressions. In order to further explore the molecular biology of this LS family, we used targeted next-generation sequencing (NGS) and Multiplex ligation dependent probe amplification (MLPA) to identify the mutation and verify the authenticity of the mutation in 15 family members. For NGS, two panels have been used, one is of MLH1, MSH2, PMS2 and MSH6 genes, the other one is of 139 cancer genetic susceptibility genes. And for the large deletions/duplications can also be identified by NGS panel, an adjusted data analysis strategy of NGS has been used. As a result, we identified a novel heterozygous large deletion in MSH6 gene that was found to be co-segregated among affected family members. This deletion results in the loss of a 3246 bp-sized fragment in MSH6 gene exons 5-9 which represents the coding regions of the MSH6 ATPase domain. This novel mutation has yet to be documented in the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) database. This mutation resulted in MSH6 protein losing gene mismatch repair function, and further caused the microsatellite instable. We speculate that this mutation may significantly impact MMR function through impaired ATP domain function. Theoretically, this proband would likely benefit from PD-1 immune check-point blockade therapy, but conversely, we observed that tumors appeared to rapidly progress after 4 sessions of anti-PD-1 treatment. Further studies to validate the effectiveness of anti-PD-1 treatments in carriers of this mutation are necessary.

Liu S, Han Z, Trivett AL, et al.
Cryptotanshinone has curative dual anti-proliferative and immunotherapeutic effects on mouse Lewis lung carcinoma.
Cancer Immunol Immunother. 2019; 68(7):1059-1071 [PubMed] Free Access to Full Article Related Publications
Lung cancer is currently the leading cause of cancer-related mortality with very limited effective therapy. Screening of a variety of traditional Chinese medicines (TCMs) for their capacity to inhibit the proliferation of human lung cancer A549 cells and to induce the in vitro maturation of human DCs led to the identification of cryptotanshinone (CT), a compound purified from the TCM Salvia miltiorrhiza Bunge. Here, CT was shown to inhibit the proliferation of mouse Lewis lung carcinoma (LLC) cells by upregulating p53, downregulating cyclin B1 and Cdc2, and, consequently, inducing G2/M cell-cycle arrest of LLC cells. In addition, CT promoted maturation of mouse and human DCs with upregulation of costimulatory and MHC molecules and stimulated DCs to produce TNFα, IL-1β, and IL-12p70, but not IL-10 in vitro. CT-induced maturation of DCs depended on MyD88 and also involved the activation of NF-κB, p38, and JNK. CT was effective in the treatment of LLC tumors and, when used in combination with low doses of anti-PD-L1, cured LLC-bearing mice with the induction of subsequent anti-LLC long-term specific immunity. CT treatment promoted T-cell infiltration and elevated the expression of genes typical of Th1 polarization in LLC tumor tissue. The therapeutic effect of CT and low doses of anti-PD-L1 was reduced by depletion of CD4 and CD8 T cells. This paper provides the first report that CT induces immunological antitumor activities and may provide a new promising antitumor immunotherapeutic.

Zuo W, Zhan Z, Ma L, et al.
Effect of ALDH2 polymorphism on cancer risk in Asians: A meta-analysis.
Medicine (Baltimore). 2019; 98(13):e14855 [PubMed] Free Access to Full Article Related Publications
Numerous studies have investigated the association between ALDH2 gene rs671G>A polymorphism and various cancer type in Asians. However, the results remain inconclusive.We conducted a comprehensive meta-analysis including 63 articles with 66 studies containing 25,682 cases and 47,455 controls retrieved by searching PubMed and Embase electronic databases up to March 5, 2018.Pooled results indicated that ALDH2 gene rs671 polymorphism was significantly associated with the overall cancer risk in Asians (homozygous model: odds ratio [OR] = 0.85, 95% confidence interval [CI] = 0.72-0.99, P = .042; heterozygous model: OR = 1.32, 95% CI = 1.14-1.52, P  < .001; recessive model: OR = 0.73, 95% CI = 0.60-0.88, P = .001; dominant model: OR = 1.32, 95% CI = 1.16-1.51, P < .001; and allele comparison model: OR = 1.11, 95% CI = 1.03-1.19, P = .004), especially in esophageal cancer and among the Chinese and the Japanese.Our results suggest that ALDH2 rs671 polymorphism is associated with the overall cancer risk in Asians. Well-designed prospective studies with more information about gene-environment interaction, such as drinking, should be conducted to validate our findings.

Moghimi M, Sobhan MR, Jarahzadeh MH, et al.
Association of GSTM1, GSTT1, GSTM3, and GSTP1 Genes Polymorphisms with Susceptibility to Osteosarcoma: a Case- Control Study and Meta-Analysis
Asian Pac J Cancer Prev. 2019; 20(3):675-682 [PubMed] Related Publications
Background: Some studies have investigated the association of GSTM1, GSTT1, GSTM3, and GSTP1 polymorphisms with susceptibility to osteosarcoma; however, these studies results are inconsistent and inconclusive. In order to drive a more precise estimation, the present case-control study and meta-analysis was performed to investigate association of GSTM1, GSTT1, GSTM3, and GSTP1 polymorphisms with osteosarcoma. Methods: Eligible articles were identified by a search of several electronic databases for the period up to May 5, 2018. Odds ratios were pooled using either fixed-effects or random effects models. Results: Finally, a total of 24 case-control studies with 2,405 osteosarcoma cases and 3,293 controls were included in the present meta-analysis. Overall, significantly increased osteosarcoma risk was found when all studies were pooled into the meta-analysis of GSTT1 (Null vs. Present: OR= 1.247 95% CI 1.020-1.524, P= 0.031) and GSTP1 polymorphism (B vs. A: OR= 8.899 95% CI 2.722-29.094, P≤0.001). In the stratified, significantly increased osteosarcoma risk was observed for GSTT1 polymorphism among Asians (Null vs. Present: OR= 1.300 95% CI 1.034-1.635, P= 0.025), but not among Caucasians. Conclusions: This meta-analysis demonstrated that GSTP1 and GSTT1 null genotype are associated with the risk of osteosarcoma. Future large welldesigned epidemiological studies are warranted to validate our results.

Li N, Fan X, Wang X, et al.
Autophagy-Related 5 Gene rs510432 Polymorphism Is Associated with Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Virus Infection.
Immunol Invest. 2019; 48(4):378-391 [PubMed] Related Publications
BACKGROUND: Despite the identification of autophagy-related protein 5 (ATG5) as a molecule involved in the activated autophagy machinery during hepatitis B virus (HBV) infection and hepatocarcinogenesis, the consequences of ATG5 mutation carriage for patients with chronic HBV infection remain unclear. This study examined the association of ATG5 polymorphisms with HBV-related diseases including hepatocellular carcinoma (HCC).
PATIENTS AND METHODS: Two functionally relevant polymorphisms ATG5 rs573775 and rs510432 were genotyped by ligase detection reaction-polymerase chain reaction in 403 patients with chronic HBV infection (171 chronic hepatitis, 119 cirrhosis and 113 HCC) and 196 healthy controls. Univariate and multivariate logistic regression was performed to evaluate factors associated with HCC.
RESULTS: The rs573775 genotype and allele frequencies had no significant differences between patients with different clinical diseases. However, HCC patients had significantly higher frequency of rs510432 genotype AA (odds ratio [OR] 2.185, 95% confidence interval [CI] 1.042-4.581, P = 0.037, P value by Bonferroni correction [P
CONCLUSION: These results indicate that rs510432 genotypes AA+GA are associated with disease progression and HCC risk in chronic HBV infection, providing novel evidence for a role of ATG5 in the pathogenesis of HBV-related HCC.
ABBREVIATIONS: HBV: hepatitis B virus; HCC hepatocellular carcinoma; TNFSF10: tumor necrosis factor superfamily member 10; ATG5: autophagy-related protein 5; DNA: deoxyribonucleic acid; LDR-PCR: ligase detection reactions-polymerase chain reaction; PCR: polymerase chain reaction; SLE: systemic lupus erythematosus; BD: Behçet's disease; IL-10: interlukin-10; LPS: lipopolysaccharide; PBMC: peripheral blood mononuclear cells; CWP: coal workers' pneumoconiosis; TNF-α: tumor necrosis factor-α.

Lawrenson K, Song F, Hazelett DJ, et al.
Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.
Gynecol Oncol. 2019; 153(2):343-355 [PubMed] Related Publications
OBJECTIVE: Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women.
METHODS: Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations.
RESULTS: At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 × 10
CONCLUSION: While some risk loci were shared between East Asian and European populations, others were population-specific, indicating that the landscape of EOC risk in Asian women has both shared and unique features compared to women of European ancestry.

Chen Z, Zuo X, Pu L, et al.
Hypomethylation-mediated activation of cancer/testis antigen KK-LC-1 facilitates hepatocellular carcinoma progression through activating the Notch1/Hes1 signalling.
Cell Prolif. 2019; 52(3):e12581 [PubMed] Related Publications
OBJECTIVES: Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen reactivated in several human malignancies. So far, the major focus of studies on KK-LC-1 has been on its potential as diagnostic biomarker and immunotherapy target. However, its biological functions and molecular mechanisms in cancer progression remain unknown.
MATERIALS AND METHODS: Expression of KK-LC-1 in HCC was analysed using RT-qPCR, Western blot and immunohistochemistry. The roles of KK-LC-1 on HCC progression were examined by loss-of-function and gain-of-function approaches. Pathway inhibitor DAPT was employed to confirm the regulatory effect of KK-LC-1 on the downstream Notch signalling. The interaction of KK-LC-1 with presenilin-1 was determined by co-immunoprecipitation. The association of CpG island methylation status with KK-LC-1 reactivation was evaluated by methylation-specific PCR, bisulphite sequencing PCR and 5-Aza-dC treatment.
RESULTS: We identified that HCC tissues exhibited increased levels of KK-LC-1. High KK-LC-1 level independently predicted poor survival outcome. KK-LC-1 promoted cell growth, migration, invasion and epithelial-mesenchymal transition in vitro and in vivo. KK-LC-1 modulated the Notch1/Hes1 pathway to exacerbate HCC progression through physically interacting with presenilin-1. Upregulation of KK-LC-1 in HCC was attributed to hypomethylated CpG islands.
CONCLUSIONS: This study identified that hypomethylation-induced KK-LC-1 overexpression played an important role in HCC progression and independently predicted poor survival. We defined the KK-LC-1/presenilin-1/Notch1/Hes1 as a novel signalling pathway that was involved in the growth and metastasis of HCC.

Liu J, Tang W, Lin W, et al.
Lack of Association Between CTLA-4 Genetic Polymorphisms and Noncardiac Gastric Cancer in a Chinese Population.
DNA Cell Biol. 2019; 38(5):443-448 [PubMed] Related Publications
Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a key negative immunoregulatory molecule with characteristics of gene polymorphisms. Genetically predisposed CTLA-4 alteration in humans was associated with gastric cancer (GC) development. To explore the association of CTLA-4 polymorphism with susceptibility of noncardiac GC (NCGC), 490 NCGC patients and 1476 control individuals were studied. Four CTLA-4 polymorphisms were genotyped with SNPscan genotyping assays and the haplotypes were constructed with SHESIS software. Frequencies of the CTLA-4 haplotypes were estimated using an expectation-maximization algorithm. The CTLA-4 polymorphism genotype distribution and allele frequencies were not significantly different between the NCGC patients and the control subjects. The CTLA-4 haplotypes did not exhibit a significantly increased risk for NCGC patients. Adjusting status of age, sex, smoking status, alcohol use, and body mass index could not moderate any of the relationships. Data suggested that CTLA-4 polymorphisms (rs3087243, rs16840252, rs733618, and rs231775) were not significantly associated with the risk of NCGC in this Chinese population studied.

Huang J, Wei Y, Zhou X, et al.
The association between survivin -31G>C polymorphism and susceptibility to sporadic colorectal cancer in a Southern Chinese population.
J Cancer Res Ther. 2019 Jan-Mar; 15(1):82-86 [PubMed] Related Publications
Background: The case-control study aimed to investigate the association between the -31G>C polymorphism in the promoter of survivin gene and the susceptibility to sporadic colorectal cancer (CRC) in a Southern Chinese population.
Materials and Methods: The study was carried out on 711 healthy controls and 702 CRC cases of a Southern Chinese population. Survivin gene -31G>C genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The association between CRC risk and -31G>C genetic polymorphism was estimated using an unconditional logistic regression model.
Results: The number of CC genotype carried in CRC patients was much higher than those of controls (P < 0.001). Compared with CC genotypes, GC, GG genotypes and -31G wild-type genotypes (i.e., GC + GG) had a significantly decreased risk of CRC (P < 0.001). In addition, survivin -31G wild-type genotypes were not associated with decreased risk of sporadic CRC patients with body mass index (BMI) ≥28.0 kg/m
Conclusion: Survivin -31G>C polymorphism is associated with sporadic CRC risk in the Southern Chinese population. The -31G wild-type genotypes and GC, GG genotypes are the independent protective factors against sporadic CRC excluding those with a BMI ≥28.0 kg/m

Zeng Y, Lai N
Association Between the CD28 c.17 +3 T>C Polymorphism (rs3116496) and Cancer Risk: An Updated Meta-Analysis.
Med Sci Monit. 2019; 25:1917-1927 [PubMed] Free Access to Full Article Related Publications
BACKGROUND Numerous studies have been conducted on whether CD28 rs3116496 polymorphism affected cancer susceptibility, and these findings have been controversial. Thus, the purpose of this study was to assess the relationship between rs3116496 and susceptibility to cancer. MATERIAL AND METHODS The research published as of October 25, 2018 were comprehensively searched in PubMed, Embase, Cochrane Library and Chinese Wanfang database, CNKI, CBM. Statistical calculations performed using Stata12.0. RESULTS Overall analyses found that rs3116496 was a risk factor for cancer (C versus T, OR=1.14, 95% CI: 1.01-1.29, PH=0.003), and the heterogeneity was moderate (I²=53.3%). In subgroup analysis results by cancer types, the analysis showed that rs3116496 was a risk factor for breast cancer and leukemia. In the subgroup analysis by ethnicity, rs3116496 was a risk factor for cancer in the Asian population. After PHWE<0.05 was deleted, the analysis showed that rs3116496 might be related to the increased risk of colorectal cancer. CONCLUSIONS Our meta-analysis confirmed that rs3116496 was significantly related to cancer risk, especially in an Asian population, and was strongly correlated with the increased risk of breast cancer, leukemia and colorectal cancer.

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