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:VEGA, OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:alpha-methylacyl-CoA racemase
Source:NCBIAccessed: 16 March, 2017


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

Cancer Overview

Research Indicators

Publications Per Year (1992-2017)
Graph generated 16 March 2017 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.

  • Young Adult
  • Cancer RNA
  • Messenger RNA
  • Single Nucleotide Polymorphism
  • Differential Diagnosis
  • Case-Control Studies
  • Cohort Studies
  • Renal Cell Carcinoma
  • Kidney Cancer
  • Translocation
  • Chromosome 5
  • Immunohistochemistry
  • Biomarkers, Tumor
  • Papillary Carcinoma
  • Tumor Antigens
  • Microscopy, Electron, Transmission
  • Androgen Receptors
  • Gene Expression Profiling
  • Membrane Proteins
  • Disease Progression
  • Neoplasm Proteins
  • Prostate Cancer
  • Gene Dosage
  • Terminology as Topic
  • Oligonucleotide Array Sequence Analysis
  • Staging
  • CGH
  • Prostatectomy
  • Biopsy
  • Adenocarcinoma
  • Neoplasm Metastasis
  • Prostate
  • Cancer Gene Expression Regulation
  • Neoplasm Grading
  • Genotype
  • Genetic Predisposition
  • FISH
  • Molecular Sequence Data
  • Trans-Activators
  • Prostate-Specific Antigen
Tag cloud generated 16 March, 2017 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)

Chang JS, Hsiao JR, Chen CH
ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective.
J Biomed Sci. 2017; 24(1):19 [PubMed] Free Access to Full Article Related Publications
The occurrence of more than 200 diseases, including cancer, can be attributed to alcohol drinking. The global cancer deaths attributed to alcohol-consumption rose from 243,000 in 1990 to 337,400 in 2010. In 2010, cancer deaths due to alcohol consumption accounted for 4.2% of all cancer deaths. Strong epidemiological evidence has established the causal role of alcohol in the development of various cancers, including esophageal cancer, head and neck cancer, liver cancer, breast cancer, and colorectal cancer. The evidence for the association between alcohol and other cancers is inconclusive. Because of the high prevalence of ALDH2*2 allele among East Asian populations, East Asians may be more susceptible to the carcinogenic effect of alcohol, with most evidence coming from studies of esophageal cancer and head and neck cancer, while data for other cancers are more limited. The high prevalence of ALDH2*2 allele in East Asian populations may have important public health implications and may be utilized to reduce the occurrence of alcohol-related cancers among East Asians, including: 1) Identification of individuals at high risk of developing alcohol-related cancers by screening for ALDH2 polymorphism; 2) Incorporation of ALDH2 polymorphism screening into behavioral intervention program for promoting alcohol abstinence or reducing alcohol consumption; 3) Using ALDH2 polymorphism as a prognostic indicator for alcohol-related cancers; 4) Targeting ALDH2 for chemoprevention; and 5) Setting guidelines for alcohol consumption among ALDH2 deficient individuals. Future studies should evaluate whether these strategies are effective for preventing the occurrence of alcohol-related cancers.

Gu HF, Mou M, Liang ZG, et al.
The association between paraoxonase 1 gene polymorphisms and polycystic ovarian syndrome.
Cell Mol Biol (Noisy-le-grand). 2016; 62(14):44-47 [PubMed] Related Publications
Some studies investigated the association of paraoxonase 1 (PON1) polymorphisms with polycystic ovarian syndrome (PCOS) risk. However, the result was still inconsistent. The aim of this study was to investigate whether there is an association between the PON1 polymorphisms and PCOS risk. Electronic databases, such as PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) databases, were searched for identification of the studies. The associations between PON1 polymorphisms and PCOS risk was quantified using ORs with 95% CIs. A total of 8 eligible studies with 2272 cases and 1811 controls were included in this meta-analysis. PON1 Leu55Met polymorphism was associated with a significantly increased risk of PCOS (OR=1.31; 95%CI, 1.10-1.55). However, no association was found in Asians and Caucasians (Table 2). We also found that PON1 Q192R polymorphism was associated with a significantly increased risk of PCOS (OR=1.81; 95%CI, 1.17-2.82). Additionally, this polymorphism increased PCOS risk in Asians (OR=1.26; 95%CI, 1.13-1.41). Furthermore, PON1 C108T polymorphism showed increased PCOS risk (OR=1.46; 95%CI, 1.08-1.97). No association between this polymorphism and PCOS risk was found in Asians and Caucasians. In conclusion, this meta-analysis suggested that PON1 polymorphisms were associated with PCOS risk.

Bhat AA, Wani HA, Ishaq S, et al.
Promoter Hypermethylation and Its Impact on Expression of MGMT Gene in the GIT Malignant Patients of Kashmiri Origin.
Cancer Invest. 2017; 35(2):116-121 [PubMed] Related Publications
Epigenetic alterations, in addition to multiple gene abnormalities, are involved in the genesis and progression of human cancers. Gastrointestinal tract (GIT) cancer is a major medical and economic burden worldwide. Aberrant methylation of CpG islands within promoter regions is associated with transcriptional inactivation of various tumor suppressor genes. Although a number of cancer-associated genes have been found to be hypermethylated in GIT cancer, valuable methylation markers for early diagnosis and prognostic evaluation of this cancer remain largely unknown. O6-methyguanine DNA methyltransferase (MGMT) is a DNA-repair gene that removes mutagenic and cytotoxic adducts from the O6 position of guanine induced by alkylating agents. MGMT promoter hypermethylation and reduced expression have been found in some primary human carcinomas. We studied DNA methylation of CpG islands of the MGMT gene and its relation with MGMT protein expression in human GIT carcinomas. A total of 210 GIT tumor samples and 90 adjacent normal tissues were analyzed for MGMT promoter methylation by methylation-specific polymerase chain reaction after bisulfite modification of DNA and same samples were analyzed for MGMT protein expression by Western blotting. The methylation frequencies of MGMT gene promoter were 41.4%, 34.2%, and 44.2% in stomach, esophageal, and colorectal cancer cases while as 16.6, 13.3, and 13.3 in respective controls. MGMT protein was found downregulated in controls of all GIT. The results suggest that methylation at CpG islands of MGMT may be responsible for the downregulation of MGMT protein expression in GIT cancers.

Liu Q, Tong D, Yuan W, et al.
Different RET gene mutation-induced multiple endocrine neoplasia type 2A in 3 Chinese families.
Medicine (Baltimore). 2017; 96(3):e5967 [PubMed] Free Access to Full Article Related Publications
BACKGROUD: Multiple endocrine neoplasia type 2A (MEN2A) is a condition with inherited autosomal dominant mutations in RET (rearranged during transfection) gene that predisposes the carrier to extremely high risk of medullary thyroid cancer (MTC) and other MEN2A-associated tumors such as parathyroid cancer and/or pheochromocytoma. Little is reported about MEN2A syndrome in the Chinese population.
METHODS: All members of the 3 families along with specific probands of MEN2A were analyzed for their clinical, laboratory, and genetic characteristics. Exome sequencing was performed on the 3 probands, and specific mutation in RET was further screened on each of the family members.
RESULTS: Different mutations in the RET gene were identified: C634S in Family 1, C611Y in Family 2, and C634Y in Family 3. Proband 1 mainly showed pheochromocytoma with MTC, both medullary thyroid carcinoma and pheochromocytoma were seen in proband 2, and proband 3 showed medullary thyroid carcinoma.
CONCLUSION: The genetic evaluation is strongly recommended for patients with a positive family history, early onset of age, or multiple sites of masses. If the results verified the mutations of RET gene, thyroidectomy should be undertaken as the guide for better prognosis.

Gai L, Liu H, Cui JH, et al.
The allele combinations of three loci based on, liver, stomach cancers, hematencephalon, COPD and normal population: A preliminary study.
Gene. 2017; 605:123-130 [PubMed] Related Publications
The purpose of this study was to examine the specific allele combinations of three loci connected with the liver cancers, stomach cancers, hematencephalon and patients with chronic obstructive pulmonary disease (COPD) and to explore the feasibility of the research methods. We explored different mathematical methods for statistical analyses to assess the association between the genotype and phenotype. At the same time we still analyses the statistical results of allele combinations of three loci by difference value method and ratio method. All the DNA blood samples were collected from patients with 50 liver cancers, 75 stomach cancers, 50 hematencephalon, 72 COPD and 200 normal populations. All the samples were from Chinese. Alleles from short tandem repeat (STR) loci were determined using the STR Profiler plus PCR amplification kit (15 STR loci). Previous research was based on combinations of single-locus alleles, and combinations of cross-loci (two loci) alleles. Allele combinations of three loci were obtained by computer counting and stronger genetic signal was obtained. The methods of allele combinations of three loci can help to identify the statistically significant differences of allele combinations between liver cancers, stomach cancers, patients with hematencephalon, COPD and the normal population. The probability of illness followed different rules and had apparent specificity. This method can be extended to other diseases and provide reference for early clinical diagnosis.

Agnihotri V, Gupta A, Kumar R, et al.
Promising link of HLA-G polymorphism, tobacco consumption and risk of Head and Neck Squamous Cell Carcinoma (HNSCC) in North Indian population.
Hum Immunol. 2017; 78(2):172-178 [PubMed] Related Publications
Human leukocyte antigen (HLA-G) is a potent immune-tolerant molecule and has a critical role in various pathological conditions of cancer. The aim of the study was to analyze the association of HLA-G polymorphism as a risk factor in Head and Neck Squamous Cell Carcinoma (HNSCC). The HLA-G polymorphism at 3'UTR 14bp INDEL (rs371194629) and +3142G/C (rs1063320) were studied in 383 HNSCC patients and 383 ethnically similar-aged healthy controls in North Indian population. The genotyping study of two polymorphisms of HLA-G was documented using DNA-PAGE and RFLP-PCR method. 14bp INDEL Del/Ins, Ins/Ins genotype and Ins allele were more pronounced in HNSCC patients in compared to controls. Whereas, +3142 C/C genotype and C allele were associated with risk factors in HNSCC. Furthermore, the dual effect of polymorphisms; both variants (Del/Ins-Ins/Ins & G/C-C/C) carrying loci was significantly (OR=2.78) associated with the disease compared to one variant (Del/Del-G/C or Del/Del-C/C or Ins/Ins-G/G). Moreover, both polymorphisms showed promising link in terms of tobacco influence on HNSCC risk. It can be concluded that this study first time reports that C/C, Del/Ins and Ins/Ins genotype as well as C and Ins allele could be major risk factors with strong impact of tobacco for HNSCC in North Indian population.

Peckova K, Martinek P, Pivovarcikova K, et al.
Cystic and necrotic papillary renal cell carcinoma: prognosis, morphology, immunohistochemical, and molecular-genetic profile of 10 cases.
Ann Diagn Pathol. 2017; 26:23-30 [PubMed] Related Publications
Conflicting data have been published on the prognostic significance of tumor necrosis in papillary renal cell carcinoma (PRCC). Although the presence of necrosis is generally considered an adverse prognostic feature in PRCC, we report a cohort of 10 morphologically distinct cystic and extensively necrotic PRCC with favorable biological behavior. Ten cases of type 1 PRCC with a uniform morphologic pattern were selected from the 19 500 renal tumors, of which 1311 were PRCCs in our registry. We focused on precise morphologic diagnosis supported by immunohistochemical and molecular-genetic analysis. Patients included 8 men and 2 women with an age range of 32-85 years (mean, 62.6 years). Tumor size ranged from 6 to 14 cm (mean, 9.4 cm). Follow-up data were available in 7 patients, ranging from 0.5 to 14 years (mean, 4 years). All tumors were spherical, cystic, and circumscribed by a thick fibrous capsule, filled with hemorrhagic/necrotic contents. Limited viable neoplastic tissue was present only as a thin rim in the inner surface of the cyst wall, consistent with type 1 PRCC. All cases were positive for AMACR, OSCAR, CAM 5.2, HIF-2, and vimentin. Chromosome 7 and 17 polysomy was found in 5 of 9 analyzable cases, 2 cases demonstrated chromosome 7 and 17 disomy, and 1 case showed only chromosome 17 polysomy. Loss of chromosome Y was found in 5 cases, including 1 case with disomic chromosomes 7 and 17. No VHL gene abnormalities were found. Papillary renal cell carcinoma type 1 can present as a large hemorrhagic/necrotic unicystic lesion with a thick fibroleiomyomatous capsule. Most cases showed a chromosomal numerical aberration pattern characteristic of PRCC. All tumors followed a nonaggressive clinical course. Large liquefactive necrosis should not necessarily be considered an adverse prognostic feature, particularly in a subset of type 1 PRCC with unilocular cysts filled with necrotic/hemorrhagic material.

Gan WY, Li HM, Zhang YG, et al.
Association between IL18-607C/A and -137G/C polymorphisms and susceptibility to non-small cell lung cancer in a Chinese population.
Genet Mol Res. 2016; 15(4) [PubMed] Related Publications
Lung cancer is one of the main causes of cancer-related mortality in males and females worldwide. A pleiotropic effect has been observed in the interleukin 18 gene (IL18); its effects include the activation of natural killer cell cytotoxicity and the promotion of the Th1 immune response through the alteration of the expression of interferon-γ and TNF-α in humans. IL18 is therefore involved in the elimination of tumor cells in the human body. We recruited 357 patients with non-small cell lung cancer (NSCLC) and 414 controls to evaluate the correlation between two genetic variations (IL18-607C/A and IL18-137G/C) and the pathogenesis of NSCLC. We used polymerase chain reaction-restriction fragment length polymorphism to genotype IL18-607C/A and IL18-137G/C. Statistical analysis revealed that individuals harboring the AA genotype of IL18-607C/A had an increased risk of NSCLC compared to those harboring the CC genotype (OR = 2.20, 95%CI = 1.30-3.74). Individuals expressing the A allele of IL18-607C/A had an elevated risk of developing NSCLC compared to those expressing the C allele (OR = 1.31, 95%CI = 1.06-1.62). In summary, our analysis shows that the IL18-607C/A genetic variation is related to the risk of NSCLC, whereas the IL18-137G/C variation is not. Therefore, the IL18-607C/A variation is related to the pathogenesis of NSCLC in the Chinese population studied.

Li L, Tang XY, Ye LM, et al.
Investigation on the association between IL-10 C819T gene polymorphisms and susceptibility to gastric cancer.
Genet Mol Res. 2016; 15(4) [PubMed] Related Publications
We conducted a case-control study to investigate the association between the interleukin-10 (IL-10) C819T polymorphism and susceptibility to gastric cancer in a Chinese population. A total of 157 patients with gastric cancer and 249 controls were consecutively enrolled from the Guizhou Provincial People's Hospital between October 2012 and February 2015. The polymerase chain reaction-restriction fragment length polymorphism technique was used to genotype for IL-10 C819T. As determined by χ(2)-test, there was a significant difference in genotype distributions of IL-10 C819T between gastric cancer patients and controls (χ(2) = 7.09; P = 0.03). Based on unconditional logistic regression analysis, the TT genotype of IL-10 C819T was significantly associated with increased risk of gastric cancer when compared with that of the CC genotype [odds ratio (OR) = 2.24; 95% confidence interval (CI) = 1.17-4.26; P = 0.008]. In a dominant model, we found that the CT + TT genotype of IL-10 C819T was associated with susceptibility to gastric cancer compared to that of the CC genotype (OR = 1.63; 95%CI = 1.02-2.64). In a recessive model, the TT genotype of IL-10 C819T was correlated with a higher risk of gastric cancer when compared with that of the CC + CT genotype (OR = 1.75; 95%CI = 1.01-3.02). In conclusion, our study suggests that the IL-10 C819T polymorphism is associated with an increased risk of gastric cancer in co-dominant, dominant, and recessive models.

Grünebach F, Huster AL, Vogel W, Klein R
Confirmation and next-generation sequencing of allele HLA-B*35:279 found in a family of a leukaemia patient with Western Asia origin.
Int J Immunogenet. 2017; 44(1):32-34 [PubMed] Related Publications
The confirmation of novel allele HLA-B*35:279 in a family of a leukaemia patient with Western Asia origin is reported. Moreover, next-generation sequencing (NGS) resulted in whole-gene sequence data and revealed the inheritance of HLA-B*35:279 on the paternal haplotype.

Wu Y, Zhang C, Xu W, et al.
CXC motif chemokine receptor 4 gene polymorphism and cancer risk.
Medicine (Baltimore). 2016; 95(49):e5317 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Previous epidemiological studies have reported the relationship between CXC motif chemokine receptor 4 (CXCR4) synonymous polymorphism (rs2228014), and risk of cancer, but the results remained conflicting and controversial. Therefore, this study was devised to evaluate the genetic effects of the rs2228014 polymorphism on cancer risk in a large meta-analysis.
METHODS: The computer-based databases (EMBASE, Web of Science, and PubMed) were searched for all relevant studies evaluating rs2228014 and susceptibility to cancer. In the analysis, pooled odds ratios (ORs) with its corresponding 95% confidence intervals (CIs) were calculated in 5 genetic models to assess the genetic risk. Egger regression and Begg funnel plots test were conducted to appraise the publication bias.
RESULTS: Data on rs2228014 polymorphism and overall cancer risk were available for 3684 cancer patients and 5114 healthy controls participating in 11 studies. Overall, a significantly increased risk of cancer was associated with rs2228014 polymorphism in homozygote model (OR = 2.01, 95% CI: 1.22-3.33) and in recessive model (OR = 1.97, 95% CI: 1.23-3.16). When stratified by ethnicity, the results were positive only in Asian populations (heterozygote model: OR = 1.36, 95% CI: 1.13-1.65; homozygote model: OR = 2.43, 95% CI: 1.21-4.91; dominant model: OR = 1.47, 95% CI: 1.13-1.90; recessive model: OR = 2.25, 95% CI: 1.13-4.48; and allele model: OR = 1.48, 95% CI: 1.10-1.99). Besides, in the subgroup analysis by source of control, the result was significant only in population-based control (homozygote model: OR = 2.39, 95% CI: 1.06-5.40; recessive model: pooled OR = 2.24, 95% CI: 1.02-4.96).
CONCLUSION: In general, our results first indicated that the rs2228014 polymorphism in CXCR4 gene is correlated with an increased risk of cancer, especially among Asian ethnicity. Large, well-designed epidemiological studies are required to verify the current findings.

Azizi Tabesh G, Izadi P, Fereidooni F, et al.
The High Frequency of PIK3CA Mutations in Iranian Breast Cancer Patients.
Cancer Invest. 2017; 35(1):36-42 [PubMed] Related Publications
In breast cancer, somatic mutations of PIK3CA oncogene are common. We investigated the mutational status of exons 9 and 20 of the PIK3CA gene by polymerase chain reaction and direct sequencing in 80 breast tumors, and observed that 45% of these contained PIK3CA mutations in the mentioned exons. These mutations were found more in progesterone receptor positive and Her2- tumors, but this association did not reach a statistically significant level. Also, we observed a significant association between PIK3CA mutations and low-grade tumors. In our study, PIK3CA mutations were related to good and moderate prognosis in breast cancer patients.

Wang T, Liang Y, Thakur A, et al.
Expression and clinicopathological significance of S100 calcium binding protein A2 in lung cancer patients of Chinese Han ethnicity.
Clin Chim Acta. 2017; 464:118-122 [PubMed] Related Publications
BACKGROUND: S100 family of calcium-binding proteins plays a significant role in the process of many kinds of tumors, including lung cancer. As an important member of this family, S100 calcium binding protein A2 (S100A2) has been confirmed to be associated with many biological processes, and has an abnormal expression in non-small cell lung cancer (NSCLC). However, the S100A2 status in lung cancer is still controversial and undefined.
METHODS: We evaluated the pattern and distribution of S100A2 in 109 cases of lung cancer, including five histological types (47 adenocarcinoma, 46 squamous cell carcinoma, 7 small cell carcinoma, 3 large cell carcinoma, and 6 atypical carcinoid), and 30 cases of paired adjacent normal lung tissues by means of immunohistochemistry.
RESULTS: Compared with the normal tissues (0/30), S100A2 experienced a dramatically upward trend of positive expression in lung cancer, with a positive rate of 68/109 (P<0.001). Specifically, squamous cell carcinoma, with 34/12, had the highest expression ratio, followed by large cell carcinoma (2/1), adenocarcinoma (31/16), and atypical carcinoid (1/5) respectively, while no S100A2 protein was detected in small cell carcinoma. Meanwhile, we firstly demonstrated that the high expression of S100A2 was significantly associated with the incidence of lymph node metastasis in adenocarcinoma (P=0.013).
CONCLUSIONS: The association between high S100A2 expression and NSCLC at the level of tissue, and S100A2 may serve as an effective biomarker for the diagnosis and prognosis of NSCLC in future.

Zheng J, Zhang R, Zhu J, et al.
Lack of Associations between XPC Gene Polymorphisms and Neuroblastoma Susceptibility in a Chinese Population.
Biomed Res Int. 2016; 2016:2932049 [PubMed] Free Access to Full Article Related Publications
Neuroblastoma is one of the most malignant solid tumors in infants and young children. No more than 40% of neuroblastoma patients can survive for longer than five years after it has been diagnosed. XPC protein is a pivotal factor that recognizes DNA damage and starts up the nucleotide excision repair (NER) in mammalian cells. This makes up the first group to defend against the cancer. Previous studies have identified that XPC gene polymorphisms were associated with various types of cancer. However, the associations between XPC gene polymorphisms and neuroblastoma risk have not yet been studied. We investigated the associations between three XPC gene polymorphisms (rs2228001 A>C, rs2228000 C>T, and rs2229090 G>C) and neuroblastoma risk with 256 neuroblastoma patients and 531 healthy controls in a Chinese Han population. Odds ratios and 95% confidence intervals were used to access the association between these three polymorphisms and neuroblastoma risk. No significant association was detected between these three polymorphisms and neuroblastoma risk in the overall analysis as well as in the stratification analysis. These results suggest that none of these three polymorphisms may be associated with the risk of neuroblastoma in the Chinese Han population.

Kader F, Ghai M
DNA methylation-based variation between human populations.
Mol Genet Genomics. 2017; 292(1):5-35 [PubMed] Related Publications
Several studies have proved that DNA methylation affects regulation of gene expression and development. Epigenome-wide studies have reported variation in methylation patterns between populations, including Caucasians, non-Caucasians (Blacks), Hispanics, Arabs, and numerous populations of the African continent. Not only has DNA methylation differences shown to impact externally visible characteristics, but is also a potential biomarker for underlying racial health disparities between human populations. Ethnicity-related methylation differences set their mark during early embryonic development. Genetic variations, such as single-nucleotide polymorphisms and environmental factors, such as age, dietary folate, socioeconomic status, and smoking, impacts DNA methylation levels, which reciprocally impacts expression of phenotypes. Studies show that it is necessary to address these external influences when attempting to differentiate between populations since the relative impacts of these factors on the human methylome remain uncertain. The present review summarises several reported attempts to establish the contribution of differential DNA methylation to natural human variation, and shows that DNA methylation could represent new opportunities for risk stratification and prevention of several diseases amongst populations world-wide. Variation of methylation patterns between human populations is an exciting prospect which inspires further valuable research to apply the concept in routine medical and forensic casework. However, trans-generational inheritance needs to be quantified to decipher the proportion of variation contributed by DNA methylation. The future holds thorough evaluation of the epigenome to understand quantification, heritability, and the effect of DNA methylation on phenotypes. In addition, methylation profiling of the same ethnic groups across geographical locations will shed light on conserved methylation differences in populations.

Oliveira JS, Ferreira RS, Santos LM, et al.
Self-declared ethnicity and genomic ancestry in prostate cancer patients from Brazil.
Genet Mol Res. 2016; 15(4) [PubMed] Related Publications
Some studies of polymorphisms in prostate cancer (PCa) analyze individuals in a uniform manner, regardless of genetic ancestry. However, PCa aggressiveness differs between subjects of African descent and those of European extraction. Thus, genetic ancestry analysis may be used to detect population stratification in case-control association studies. We genotyped 11 ancestry informative markers to estimate the contributions of African, European, and Amerindian ancestries in a case-control sample of 213 individuals from Bahia State, Northeast Brazil, including 104 PCa patients. We compared this data with self-reported ancestry and the stratification of cases by PCa aggressiveness according to Gleason score. A larger African genetic contribution (44%) was detected among cases, and a greater European contribution (61%) among controls. Self-declaration data revealed that 74% of PCa patients considered themselves non-white (black and brown), and 41.3% of controls viewed themselves as white. Our data showed a higher degree of European ancestry among fast-growing cancer cases than those of intermediate and slow development. This differs from many previous studies, in which the prevalence of African ancestry has been reported for all grades. Differences were observed between degrees of PCa aggressiveness in terms of genetic ancestry. In particular, the greater European contribution among patients with high-grade PCa indicates that a population's genetic structure can influence case-control studies. This investigation contributes to our understanding of the genetic basis of tumor aggressiveness among groups of different genetic ancestries, especially admixed populations, and has significant implications for the assessment of inter-population heterogeneity in drug treatment effects.

Mukoyama N, Yoshimi A, Goto A, et al.
An Analysis of Behavioral and Genetic Risk Factors for Chemotherapy-Induced Nausea and Vomiting in Japanese Subjects.
Biol Pharm Bull. 2016; 39(11):1852-1858 [PubMed] Related Publications
There are individual differences in the frequency of chemotherapy-induced nausea and vomiting (CINV) in cancer patients. We investigated the individual variability in susceptibility to CINV with focus on both behavioral factors and genetic factors in Japanese cancer patients. We performed a prospective study to investigate the association between patient attributes (backgrounds and habits as well as gene polymorphisms) and anorexia, nausea, or vomiting in 55 Japanese cancer patients undergoing chemotherapy at Nagoya University Hospital. We found that gender (female), use of non-steroidal anti-inflammatory drugs, susceptibility to motion sickness, and anxiety were associated with the frequency of CINV. Gene polymorphisms of rs1076560 (dopamine D2 receptor gene), rs6766410 (serotonin 5-HT3C receptor gene) and rs4680 (catechol-O-methyltransferase gene) were also associated. Our data suggest that these attributes may thus be risk factors for CINV. Our results provide novel information that can be used to predict the incidence of CINV in Japanese patients undergoing chemotherapy; this can help provide a substantial improvement in supportive care for patients with different types of cancer.

Williams AS, Greer W, Bethune D, et al.
ALK+ lung adenocarcinoma in never smokers and long-term ex-smokers: prevalence and detection by immunohistochemistry and fluorescence in situ hybridization.
Virchows Arch. 2016; 469(5):533-540 [PubMed] Related Publications
ALK gene rearrangements are identified in 2-5 % of all non-small cell lung cancer and are more common in lifetime non-smokers with adenocarcinoma, but the prevalence of ALK rearrangements is not as well characterized in long-term ex-smokers (quit >10 years prior to diagnosis). Accurate and timely diagnosis of ALK-rearranged tumors is of clinical importance given the remarkable response to targeted inhibitors. ALK gene rearrangement may be detected by fluorescence in situ hybridization (FISH), and abnormal expression of ALK protein may be detected by immunohistochemistry (IHC), the latter of which is faster and less expensive. The aim of this study is to evaluate the prevalence of ALK rearrangement in non-smokers and long-term ex-smokers with lung adenocarcinoma and to assess the performance of IHC for the detection of ALK+ tumors when compared to FISH. Two hundred fifty-one cases of resected lung adenocarcinoma were retrospectively reviewed, including non-smokers (n = 79) or long-term ex-smokers (n = 172). ALK IHC and ALK FISH were performed on each case. Four cases demonstrated ALK rearrangement by FISH (4/251; 1.6 %). All cases were non-smokers (4/79; 5.1 %), and all were positive for ALK by IHC. No additional cases were considered positive by IHC, and only 26 (10.4 %) cases were considered equivocal using a conservative approach to interpretation, resulting in a sensitivity of 100 % and specificity of 89.5 %. ALK rearrangement was not observed in lung adenocarcinoma arising in long-term ex-smokers, whereas it is seen in up to 5.1 % of lifetime non-smokers. ALK IHC using the 5A4 antibody demonstrates high sensitivity, supporting its use as a screening test.

Endo Y, Dong Y, Kondo N, et al.
HER2 mutation status in Japanese HER2-positive breast cancer patients.
Breast Cancer. 2016; 23(6):902-907 [PubMed] Related Publications
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) gene amplification/overexpression is a major therapeutic target in breast cancer, and has been introduced as a predictive biomarker to identify patients who may benefit from therapy with anti-HER2 agents. HER2 somatic mutations have been reported, and these may influence the effect of HER2-targeted drugs.
METHODS: Here, we sought HER2 mutations in a group of 135 Japanese breast cancer patients with HER2-positive tumors. We analyzed HER2 mutations by direct Sanger sequencing of two major areas, the extracellular domain at position 309-310 and the kinase domain between 755 and 781.
RESULTS: Two patients with the HER2 somatic mutation S310F in the extracellular domain were found in this series. One patient with the S310F mutation had a node-negative invasive ductal carcinoma classified as HER2 2+ by the HercepTest and fluorescence in situ hybridization (FISH) positive, and which was estrogen receptor (ER)-negative and progesterone receptor (PgR)-negative. Another patient with the S310F mutation had an apocrine carcinoma with seven lymph nodes positive for metastasis, classified as HER2 3+ by the HercepTest, but which was FISH-negative, as well as ER-negative and PgR-negative. Both patients had received adjuvant single-agent trastuzumab therapy, and had no local recurrence or distant metastasis for five and three years after surgery, respectively.
CONCLUSIONS: Our data show that HER2 mutations are rare in HER2-positive Japanese breast cancer patients. The two mutations found in this study were identical, S310F. We suggest that in vitro experiments to determine whether the S310F mutation could be involved in resistance to anti-HER2 drugs are worthwhile in future.

Jiang H, Mao X, Huang X, et al.
TMPRSS2:ERG fusion gene occurs less frequently in Chinese patients with prostate cancer.
Tumour Biol. 2016; 37(9):12397-12402 [PubMed] Related Publications
Prostate cancer is the commonest male malignancy in the Western world, but its morbidity is much lower in China. The principal aim of this study was to evaluate the frequency of TMPRSS2:ERG fusion in Chinese prostate cancer patients using immunohistochemistry and reverse transcription polymerase chain (RT-PCR). In addition, we compared the ERG protein expression with TMPRSS2:ERG fusion gene. The relationship between ERG expression and clinicopathologic features was also examined. Samples from patients who underwent radical prostatectomies in Changhai Hospital (Shanghai, China) were collected and stored in ethically approved tissue banks. One hundred seventy-four prostate cancer tissue samples and 10 normal tissues were marked on standard hematoxylin-eosin (HE) sections, punched out of the paraffin blocks and inserted into a recipient block using tissue arrayer instruments. Immunohistochemistry and RT-PCR were employed to detect TMPRSS2:ERG fusion gene. ERG was highly expressed in the nuclei of endothelial cells of vessels and weak cytoplasmic staining was occasionally observed. ERG positive staining was present in 14.9 % (26/174) of the tumor samples in microarray. All benign prostate samples were found to be negative. RT-PCR results revealed that 11.1 % (15/135) were TMPRSS2:ERG fusion positive. Altogether, there was a good agreement of ERG immunostaining with the presence of TMPRSS2:ERG. However, no correlation was observed between ERG expression and age, Gleason score, stage, surgical margin, and seminal vesicle involvement in Chinese patients. In the present study, we identified a high correlation between ERG expression and ERG TMPRSS2:ERG, with 100 % sensitivity and 88.9 % specificity. The expression level of ERG was unrelated to the age, Gleason score, stage, surgical margin, and seminal vesicle involvement. Therefore, the association between ERG expression and prostate cancer based on Chinese population should be further investigated in the future.

Box A, Alshalalfa M, Hegazy SA, et al.
High alpha-methylacyl-CoA racemase (AMACR) is associated with ERG expression and with adverse clinical outcome in patients with localized prostate cancer.
Tumour Biol. 2016; 37(9):12287-12299 [PubMed] Related Publications
Alpha-methylacyl-CoA racemase (AMACR) is a well-characterized marker extensively utilized in prostate cancer (PCA) diagnosis. However, the prognostic value of AMACR expression and its relation to TMPRSS2-ERG gene rearrangement as one of the most common molecular alterations in PCA is not fully explored. AMACR expression was investigated in a cohort of 218 men with localized PCA treated by radical prostatectomy and correlated with ERG and various clinical and pathological parameters. In vitro studies assessed AMACR changes to ERG knockdown and other related genes. In addition, bioinformatics validated the significance of AMACR/ERG expression and assessed relevant genetic signatures in relation to AMACR/ERG expression. AMACR expression was significantly associated with disease progression and with ERG (p ∼0). Seventeen percent of cancer foci showed negative/weak AMACR expression while being ERG positive. High AMACR expression was significantly associated with positive surgical margins (p = 0.01), specifically in tumors with lower Gleason score <7, with ∼95 % exhibiting positive surgical margin (p = 0.008). High AMACR showed marginal association with PSA biochemical recurrence (BCR) (p = 0.06) which was slightly more pronounced in ERG-positive tumors (p = 0.04). This was validated in other public cohorts. However, in this cohort, the association with BCR was not statistically significant in multivariate analysis (p = 0.09). Using in vitro cellular models, AMACR messenger RNA (mRNA) expression, but not protein levels, showed an association with ERG expression. We report for the first time a significant association between AMACR and ERG with prognostic implication. Patients with high AMACR/ERG-positive PCA may be at higher risk for disease progression, and additional studies in larger cohorts are needed to confirm the above findings. Functional studies investigating the molecular pathways connecting AMACR and ERG may provide an additional insight into PCA progression pathways.

Cecener G, Guney Eskiler G, Egeli U, et al.
Association of PALB2 sequence variants with the risk of early-onset breast cancer in patients from Turkey.
Mol Biol Rep. 2016; 43(11):1273-1284 [PubMed] Related Publications
The PALB2 gene, has been accepted as a moderate-penetrance gene associated with breast cancer susceptibility and this gene product is involved in the DNA damage repair pathway via co-localization with BRCA2. Germline PALB2 mutations are associated with an increased breast cancer risk. However, the prevalence of the diverse types of PALB2 variants depend on the population. Thus, the aim of the present study was to determine, for the first time, the prevalence of PALB2 variants in a Turkish population of BRCA1/BRCA2-negative early-onset patients with breast cancer. In total, 223 Turkish patients with BRCA1/BRCA2 negative early-onset breast cancer and 60 unaffected women were included in the study. All the coding exons and intron/exon boundaries of PALB2 were subjected to mutational analysis by heteroduplex analysis (HDA)and DNA sequencing. Eighteen PALB2 variants were found in breast cancer patients within the Turkish population. Three variants (c.271G>A, c.404C>A and c.2981T>A) have not been previously reported. In addition, nine intronic variants were described, and this study is the first to describe the c.1685-44T>A intronic variant. The prevalence of possible pathogenic PALB2 variants was found to be 4.03 % in BRCA1/2-negative Turkish patients with early-onset breast cancer. Different variants of PALB2 have been reported in the literature, and the prevalence of these variants could different for each population. This is the first study to investigate the prevalence of PALB2 variants in Turkish patients with early-onset breast cancer.

Kumondai M, Hosono H, Orikasa K, et al.
CYP2A13 Genetic Polymorphisms in Relation to the Risk of Bladder Cancer in Japanese Smokers.
Biol Pharm Bull. 2016; 39(10):1683-1686 [PubMed] Related Publications
Tobacco-specific nitrosamines including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), which can be activated by the metabolic enzyme CYP2A13, are potent procarcinogens. Smoking plays a role in carcinogenesis in the human bladder, which expresses CYP2A13 at a relatively high level. Numerous genetic polymorphisms of CYP2A13 causing amino acid substitution might reduce CYP2A13 metabolic activity toward NNK and NNN, resulting in decreased susceptibility to bladder cancer. The aim of this study was to reveal any association between bladder cancer development and CYP2A13 genetic polymorphisms in Japanese smokers. The CYP2A13 genotype of each subject (163 bladder cancer patients and 161 controls) was determined by next-generation sequencing (NGS) of the full CYP2A13 gene. All samples were genotyped for five CYP2A13 variant alleles (CYP2A13*2, *3, *4, *6, *7). Based on biological logistic regression, the odds ratio (95% confidence interval) for the CYP2A13*1/*2 genotype was 0.34 (0.17-0.69). Thus, CYP2A13 genetic polymorphisms might play important roles in the development of bladder cancer in Japanese smokers.

Zhong Q, Wu RR, Zeng ZM
Association of ADH1B Arg47His and ALDH2 Glu487Lys polymorphisms with risk of colorectal cancer and their interaction with environmental factors in a Chinese population.
Genet Mol Res. 2016; 15(3) [PubMed] Related Publications
Human colorectal cancer (CRC) is a major worldwide health concern, and its development has been shown to be associated with alcohol intake. We carried out a study to investigate the effect of the ADH1B Arg47His and ALDH2 Glu487Lys genetic polymorphisms and their interaction with alcohol consumption on development of CRC. Between March 2013 and May 2015, a total of 274 CRC patients and 358 healthy controls were recruited. Genotyping of sequence variations was performed using the polymerase chain reaction-restriction fragment length polymorphism method. Under a co-dominant model, individuals with the ADH1B Arg47His AA genotype showed increased CRC risk compared to those carrying the GG genotype, with an adjusted odds ratio (and 95% confidence interval) of 3.37 (2.00-5.70). Moreover, under dominant and recessive models, ADH1B Arg47His variant genotypes were associated with greater susceptibility to CRC when compared with the wild-type sequence. Both polymorphisms examined were positively associated with alcohol consumption in a Spearman correlation analysis of CRC risk. In conclusion, our study suggests that the ADH1B Arg47His polymorphism, but not the ALDH2 Glu487Lys variation, may influence development of CRC in the Chinese population.

Feng R, Zhang HX, Zhang HG, Zhang CF
Role of ABCB1 C1236T, G2677T, and C3435T genetic polymorphisms in the development of acute leukemia in a Chinese population.
Genet Mol Res. 2016; 15(3) [PubMed] Related Publications
We carried out a case-control study to examine the relationship between the ATP-binding cassette subfamily B member 1 (ABCB1) gene polymorphisms C1236T, G2677T, and C3435T and risk of acute leukemia in a Chinese population. Between May 2013 and April 2015, we recruited 164 acute leukemia patients and 285 healthy controls, and determined polymorphism genotypes by polymerase chain reaction-restriction fragment length polymorphism. Using unconditional logistic regression analysis, we observed that in comparison to the wild-type sequence, the TT genotype [odds ratio (OR) = 2.15, 95% confidence interval (CI) = 1.12-4.10; P = 0.01] and the T allele (OR = 1.39, 95%CI = 1.05-1.86; P = 0.02) of ABCB1 G2677T were associated with acute leukemia susceptibility. The TT genotype (OR = 2.03, 95%CI = 1.11- 3.69; P = 0.01) and the T allele (OR = 1.39, 95%CI = 1.05-1.85; P = 0.02) of the C3435T polymorphism also increased acute leukemia risk compared to the wild-type form. However, no significant relationship was established between the ABCB1 C1236T variant and this disease. Our results suggest that the ABCB1 G2677T and C3435T sequence variations may affect susceptibility to acute leukemia.

Sun XC, Zhang AC, Tong LL, et al.
miR-146a and miR-196a2 polymorphisms in ovarian cancer risk.
Genet Mol Res. 2016; 15(3) [PubMed] Related Publications
We investigated the relationship between miR-146a and miR-196a2 genetic polymorphisms and development of ovarian cancer in a Chinese population. A total of 134 patients and 227 control subjects were involved in our study between January 2012 and October 2014 from China-Japan Union Hospital of Jilin University. Genotyping of miR-146a and miR-196a2 was accomplished by polymerase chain reaction coupled with restriction fragment length polymorphism analysis. Unconditional multiple-logistic regression analysis indicated that the GG genotype of miR-146a was associated with an increased risk of ovarian cancer when compared to the CC genotype, and the adjusted OR (95%CI) was 3.73 (1.79-7.80). Moreover, the CG+GG genotype of miR-146a was associated with an increased risk of ovarian cancer compared with the CC genotype (OR = 1.68, 95%CI = 1.06-2.66), and the GG genotype had a higher risk of ovarian cancer than the CC+CG genotype (OR = 3.02, 95%CI = 1.55-5.98). In conclusion, our study suggests that the miR-146a polymorphism is associated with increased risk of ovarian cancer and could be used as a biomarker for ovarian cancer susceptibility.

Yang LQ, Zhang Y, Sun HF
Investigation on ERCC5 genetic polymorphisms and the development of gastric cancer in a Chinese population.
Genet Mol Res. 2016; 15(3) [PubMed] Related Publications
Our study aimed to investigate the role of 2 ERCC5 promoter SNPs (rs2094258 and rs751402) in the development of gastric cancer in the Chinese population. The present hospital-based case-control study consisted of 155 patients with gastric cancer and 246 healthy controls recruited between March 2012 and December 2014. Genotyping for the rs2094258 and rs751402 polymorphic sites was carried out using polymerase chain reaction-restriction fragment length polymorphism. Statistical analyses were conducted using the SPASS version 16.0 software (SPSS, Inc., Chicago, IL, USA). As determined by the chi-square test, there was a significant difference in the genotype distributions of rs751402 between patients and controls (X(2) = 6.74, P = 0.03). By unconditional logistic regression analysis, we observed that the TT genotype in rs751402 was significantly associated with increased risk to gastric cancer as compared with the CC genotype, and the adjusted OR (95%CI) was 2.17 (1.15-4.09). Moreover, subjects carrying the T allele in rs751402 had elevated risk of developing gastric cancer when compared with those carrying the C allele, with an adjusted OR value (95%CI) of 1.47 (1.09-1.99). In conclusion, we suggest that the ERCC5 rs751402 gene polymorphism may influence the susceptibility to gastric cancer in the Chinese population.

Jiang N, Peng YP, Wang XY, et al.
Assessing the association between EFEMP1 rs3791679 polymorphism and risk of glioma in a Chinese Han population.
Genet Mol Res. 2016; 15(3) [PubMed] Related Publications
In this study, we assessed the association between the EFEMP1 rs3791679 polymorphism and glioma risk in a Chinese Han population. A total of 94 glioma patients and 206 healthy controls who conformed to the inclusion and exclusion criteria were recruited from Baogang Hospital between March 2012 and October 2014. The EFEMP1 rs3791679 gene polymorphism was assessed using a polymerase chain reaction-restriction fragment length polymorphism assay and the results were statistically analyzed using SPSS Statistics 17.0. The results of unconditional logistic regression analysis revealed that the GG genotype of EFEMP1 rs3791679 was positively correlated with increased susceptibility to glioma (adjusted OR = 2.09, 95%CI = 1.21-7.81). Moreover, the GG genotype of EFEMP1 rs3791679 was correlated with higher risk of glioma compared to the AA+GA genotype (OR = 2.60, 95%CI = 1.08-6.28) in the regressive model. In conclusion, we report that the EFEMP1 rs3791679 polymorphism influences glioma susceptibility in the Chinese Han population.

Fan SC, Zhou JG, Yin JZ
Investigation of the role of XRCC1 genetic polymorphisms in the development of gliomas in a Chinese population.
Genet Mol Res. 2016; 15(3) [PubMed] Related Publications
We conducted a study in a Chinese Han population to investigate the role of XRCC1 gene polymorphisms (Arg399Gln and Arg194Trp) with a risk of susceptibility to gliomas. Samples from 115 patients with gliomas and 228 control subjects were consecutively collected between March 2012 and December 2014. Genotype analysis of XRCC1 Arg399Gln and Arg194Trp was performed using polymerase chain reaction-restriction fragment length polymorphism assay. All the analyses were performed using the SPSS 17.0 software package. We observed that the XRCC1 Arg399Gln and Arg194Trp genotype frequencies conformed to the Hardy-Weinberg equilibrium. We observed that the Trp/Trp genotype of XRCC1 Arg194Trp was associated with an increased risk of glioma when compared to the wild-type genotype (odds ratio (OR) = 2.14, 95% confidence interval (CI) = 1.14-3.86, P = 0.03). In the dominant model, we found that the Arg/Trp + Trp/Trp genotype of XRCC1 Arg194Trp could significantly elevate the susceptibility of developing glioma (OR = 1.79, 95%CI = 1.07-0.94). However, we observed that the XRCC1 Arg399Gln genetic polymorphism did not influence the risk of glioma. In summary, we suggest that the XRCC1 Arg194Trp genetic polymorphism could be a predictive biomarker for the susceptibility to glioma in a Chinese population.

Qiu H, Wang X, Guo R, et al.
HOTAIR rs920778 polymorphism is associated with ovarian cancer susceptibility and poor prognosis in a Chinese population.
Future Oncol. 2017; 13(4):347-355 [PubMed] Related Publications
AIM: The aim of this study was to determine if HOTAIR rs920778 polymorphism is associated with ovarian cancer susceptibility and prognosis.
MATERIALS & METHODS: The data were obtained from two independent groups including 329 ovarian cancer patients and 680 cancer-free, age-matched women. Blood samples were collected and genomic DNA was extracted for genotyping.
RESULTS: TT genotype and T allele of HOTAIR rs920778 were significantly associated with a decreased ovarian cancer risk (p = 0.0004 and p < 0.0001, respectively), which associated with advanced tumor stage, lymph node metastasis and poor prognosis. Moreover, TT and TC carriers obtained a much shorter survival (p = 0.026).
CONCLUSION: These findings propose that HOTAIR rs920778 polymorphism influences ovarian cancer susceptibility and prognosis, and further studies are warranted in other populations.

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