A Model for Gastric Cancer Risk Prediction Based on MUC1 Polymorphisms and Health-risk Behaviors in a Vietnamese Population.

BACKGROUND/AIM: Although the expression of mucin 1(MUC1) and prostate stem cell antigen (PSCA) genes is correlated with gastric cancer development and progression, the utility of these two genes as biomarkers of gastric cancer prognosis still needs to be confirmed in clinical practice. This study aimed to develop a model predictive of gastric cancer that integrates several significant single nucleotide polymorphisms (SNPs) of MUC1 and PSCA genes, and some health-risk behavior factors in a Vietnamese population. PATIENTS AND METHODS: A total of 302 patients with primary gastric carcinoma and 304 healthy persons were included in a case-control study. The generalized linear model was used with the profile of age, sex, history of smoking and using alcohol, personal and family medical history of stomach diseases, and the SNPs of MUC1 and PSCA. The prognostic value of the model was assessed by the area under a receiver operating characteristic curve (AUC) and Akaike Information Criterion (AIC) values. RESULTS: In male participants, the final model, consisting of age, sex, history of smoking and using alcohol, personal and family medical history of stomach diseases and SNP MUC1 rs4072037, provided acceptable discrimination, with an AUC of 0.6374 and the lowest AIC value (539.53). In female participants, the predictive model including age, sex, history of smoking and using alcohol, personal and family medical history of stomach diseases, SNPs MUC1 rs4072037 and rs2070803 had an AUC of 0.6937 and AIC of 266.80. The calibration plots of the male model approximately fitted the ideal calibration line. CONCLUSION: The predictive model based on age, sex, medical history, and genetic and health-risk behavior factors has a high potential in determining gastric cancer. Further studies that elucidate other genetic variants should be carried out to define high-risk gastric cancer groups and propose appropriate personalized prevention.

Polymorphism of MUC1 Gene in Vietnamese Gastric Cancer Patients: A Multicenter Case-Control Study.

BACKGROUND: A few studies revealed that the polymorphisms of Mucin 1 gene have a role and significance as a susceptible factor contributing to gastric cancer. To better understand the roles of two MUC1 genotype polymorphisms of rs4072037 and rs2070803 in the development of gastric cancer in Vietnamese population, a multicenter, large-sample, case-control study was conducted to investigate the potential association of these single-nucleotide polymorphisms (SNPs) of MUC1 gene with gastric cancer risk and to evaluate the combination factors in relation with these SNPs. METHODS: This case-control study included 302 gastric cancer patients and 304 controls at four national medical hospitals between 2016 and 2018. All participants were interviewed for sociodemographic characteristics, smoking and drinking status, and personal and family history of gastric diseases. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism analysis. The association of SNPs with gastric cancer was explored using logistic regression models. RESULTS: AA genotype for rs4072037 was significantly associated with increased gastric cancer. Those with AA genotype had higher gastric cancer risk than had patients with AG (OR: 2.09, 95% CI: 1.48-2.96) and a combination of AG+GG (OR: 1.85, 95% CI: 1.33-2.56). In rs2070803, GG genotype increased gastric cancer risk when compared with AG (OR: 1.97, 95% CI: 1.39-2.80) and AG+AA (OR: 1.71, 95% CI: 1.23-2.39). AG genotypes in both SNPs decreased gastric cancer risk when compared with homogenous genotype, more specifically AA (OR: 0.51, 95% CI: 0.35-0.72) and GG (OR: 0.58, 95% CI: 0.35-0.97). These genotypes in combination with above-60-year-old age, male gender, alcoholism, and personal history of gastric disease were also significantly elevated risk factors for gastric cancer. CONCLUSIONS: rs4072037 and rs2070803 of Mucin 1 genes are two genotypic risk factors for gastric cancer. Those in combination with gender, family history, smoking, and drinking habits significantly increase the risk of gastric cancer.

Identification of three novel mutations in PCNT in vietnamese patients with microcephalic osteodysplastic primordial dwarfism type II.

BACKGROUND: Primordial dwarfism (PD) is a group of genetically heterogeneous disorders related to developmental disabilities occurring in the uterus and prolongs during all stages of life, resulting in short stature, facial deformities and abnormal brain. OBJECTIVE: To determine the exact cause of the disease in two Vietnamese patients priory diagnosed with PD by severe pre-and postnatal growth retardation with marked microcephaly and some bone abnormalities. METHODS: Whole-exome sequencing was performed for the two patients and mutations in genes related to PD were screened. Sanger sequencing was applied to examine the mutations in the patients of their families. RESULTS: Three novel mutations in the PCNT gene which have not been reported previously were identified in the two patients. Of which, two frameshift mutations (p.Thr479Profs*6 and p.Glu2742Alafs*8) were detected in patient I and one stop-gained mutation (p.Gln1907*) was detected in the patient II. These mutations may result in a truncated PCNT protein, leading to an inactivated PACT domain corresponding to residue His3138-Trp3216 of PCNT protein. Therefore, the three mutations may cause a deficiency of protein functional activity and result in the phenotypes of primordial dwarfism in the two patients. CONCLUSIONS: Clinical presentations in combination with genetic analyses supported an accurate diagnosis of the two patients with microcephalic osteodysplastic primordial dwarfism type II (MOPD II). In addition, these results have important implications for prenatal genetic screening and genetic counseling for the families.

A novel frameshift PHKA2 mutation in a family with glycogen storage disease type IXa: A first report in Vietnam and review of literature.

BACKGROUND: Glycogen storage diseases (GSDs) are clinically and genetically heterogeneous disorders. Overlapping features between liver GSDs are a major challenge in the clinical diagnosis of them. Genetic testing can provide an early and accurate diagnosis of patients suspected with GSDs. CASE PRESENTATION: In this study, we report two siblings born to healthy, non-consanguineous Vietnamese parents with hepatomegaly. The proband presented with hepatomegaly, normal spleen, elevated transaminases, without hypoglycemia, normal lactate dehydrogenase and creatine kinase. Liver biopsy revealed degeneration and swollen hepatocytes, suggesting a diagnosis with GSDs. METHODS: Whole exome sequencing was applied to identify genetic variants in the proband. Variant validation and familial co-segregation analysis were examined using Sanger sequencing. RESULTS: A novel frameshift duplication mutation c.3308_3312dupATGTC (p.L1105Mfs*11) of the PHKA2 gene was identified in the proband and his elder brother at the hemizygous state. This mutation was inherited from their mother. Their father and younger brother were normal genotype. CONCLUSIONS: The two siblings were accurately diagnosed with GSD type XIa. This is the first case report of GSD type IXa in Vietnamese patients with a mutation in the PHKA2 gene. This finding may support for genetics diagnosis of unknown cause of hepatomegaly.

Isolation of Nontuberculous Mycobacteria in Southeast Asian and African Human Immunodeficiency Virus-infected Children With Suspected Tuberculosis.

We enrolled 427 human immunodeficiency virus-infected children (median age, 7.3 years), 59.2% severely immunodeficient, with suspected tuberculosis in Southeast Asian and African settings. Nontuberculous mycobacteria were isolated in 46 children (10.8%); 45.7% of isolates were Mycobacterium avium complex. Southeast Asian origin, age 5-9 years, and severe immunodeficiency were independently associated with nontuberculous mycobacteria isolation. CLINICAL TRIALS REGISTRATION: NCT01331811.

Phycicoccus ginsengisoli sp. nov., isolated from cultivated ginseng soil.

Ginseng-cultivated soil is an excellent habitat for soil-borne bacteria to proliferate. A novel strain, DCY87T, was isolated from ginseng-cultivated soil in Gochang County, Republic of Korea, and subsequently characterized by polyphasic approach. Cells were rod shaped, non-motile, aerobic, Gram-reaction-positive, oxidase-negative and catalase-positive. 16S rRNA gene sequence analysis showed that strain DCY87T shared the highest similarity to 'Phycicoccus ochangensis' L1b-b9 (98.7 %). Closely phylogenetic relatives of strain DCY87T were identified: Phycicoccus ginsenosidimutans BXN5-13T (97.9 %), Phycicoccus soli THG-a14T (97.8 %), Phycicoccus bigeumensis MSL-03T (97.3 %), Phycicoccus cremeus V2M29T (97.3 %), Phycicoccus aerophilus 5516T-20T (97.3 %), Phycicoccus dokdonensis DS-8T (97.3 %) and Phycicoccus jejuensis KSW2-15T (97.1 %). The major polar lipids were classified as phosphatidylinositol and diphosphatidylglycerol. The major cellular fatty acids were composed of iso-C15 : 0, anteiso-C15:0, C17 : 0 and C17 : 1ω8c. The menaquinone was resolved as MK-8(H4). Strain DCY87T contained meso-diaminopimelic acid as diamino acid in the cell-wall peptidoglycan and glucose, xylose and rhamnose in the whole-cell sugar. The genomic DNA G+C content was calculated to be 72.7 mol%. DNA-DNA hybridization value between strain DCY87T and 'P. ochangensis' L1b-b9 was estimated to be 50 %. However, DNA-DNA hybridization value obtained between strain DCY87T and P. ginsenosidimutans BXN5-13T, P. soli THG-a14T and P. bigeumensis MSL-03T was well below 17 %. In general, polyphasic taxonomy demonstrated that DCY87T strain represented a novel species within the genus Phycicoccus. Accordingly, we propose the name Phycicoccus ginsengisoli sp. nov. The type strain is DCY87T (=KCTC 39635T=JCM 31016T).

Flavobacterium panacis sp. nov., isolated from rhizosphere of Panax ginseng.

A novel bacterial strain, designated DCY106(T), was isolated from soil collected from the rhizosphere of ginseng (Panax ginseng), in Gochang, Republic of Korea. Strain DCY106(T) is Gram-negative, yellow-pigmented, non-flagellate, motile, non-spore-forming, rod-shaped, and strictly aerobic. The strain grows optimally at 25-30 °C and pH 6.5-7.5. Phylogenetically, strain DCY106(T) is closely related to Flavobacterium arsenitoxidans KCTC 22507(T) (98.41 %), followed by Flavobacterium cutihirudini LMG 26922(T) (97.67 %), Flavobacterium nitrogenifigens LMG 28694(T) (97.59 %), Flexibacter auranticus LMG 3987(T) (97.38 %), Flavobacterium defluvi KCTC 12612(T) (97.21 %) and Flavobacterium chilense LMG 26360(T) (97.05 %). The 16S rRNA gene sequence similarities to all other Flavobacterium species were below 97 %. The DNA G+C content of strain DCY106(T) is 34.2 mol% and the DNA-DNA relatedness between strain DCY106(T) and F. cutihirudini LMG 26922(T), F. auranticus LMG 3987(T), F. defluvi KCTC 12612(T) and F. chilense LMG 26360(T) were below 40.0 %. The menaquinone of the type MK-6 was found to be the predominant respiratory quinone. The major polar lipids were identified as phosphatidylethanolamine, phosphatidylserine, two unidentified aminolipids (APL1, APL6) and one unidentified lipid L2. C15:0, iso-C15:0 and summed feature 3 (iso-C15:0 2OH/C16:1 ω7c) were identified as the major fatty acids present in DCY106(T). The results of physiological and biochemical tests allowed strain DCY106(T) to be differentiated phenotypically from other recognized species belonging to the genus Flavobacterium. Therefore, it is suggested that the newly isolated organism represents a novel species, for which the name Flavobacterium panacis sp. nov. is proposed with the type strain designated as DCY106(T) (= JCM 31468(T)= KCTC 42747(T)).

Paenibacillus puernese sp. nov., a ß-glucosidase-producing bacterium isolated from Pu'er tea.

A Gram-staining-positive, endospore-forming, aerobic, rod-shaped bacterium, designated as DCY97(T), was isolated from ripened Pu'er tea and was identified by using a polyphasic approach. 16S rRNA gene sequence analysis showed that strain DCY97(T) was closely related to Paenibacillus dongdonensis KUDC0114(T) (98.0 %), Paenibacillus oceanisediminis L10(T) (97.7 %), and Paenibacillus barcinonensis BP-23(T) (97.2 %). The phenotypic and chemotaxonomic characteristics of strain DCY97(T) matched with the characteristics of members belonging to the genus Paenibacillus. The major identified polar lipids included phosphatidylglycerol, phosphatidylethanolamine, and diphosphatidylglycerol. The predominant quinone was MK-7. The major fatty acids were anteiso-C15:0 (35.1 %), anteiso-C16:0 (19.0 %), and iso-C16:0 (13.9 %). The peptidoglycan cell wall was composed of meso-diaminopimelic acids, alanine, and D-glutamic acid. The genomic DNA G + C content was determined to be 46.7 mol%. The DNA-DNA relatedness between strain DCY97(T) and Paenibacillus dongdonensis KCTC 33221(T), Paenibacillus oceanisediminis KACC 16023(T), Paenibacillus barcinonensis KCTC 13019(T) were 27, 19, and 10 %, respectively. Based on the genotypic, phenotypic, and chemotaxonomic characteristics, strain DCY97(T) is considered as a novel species of the genus Paenibacillus, for which the name Paenibacillus puernese sp. nov. is proposed. The type strain is DCY97(T) (=KCTC 33596(T) = JCM 140369(T)).

Flavobacterium panaciterrae sp. nov., a ß-glucosidase producing bacterium with ginsenoside-converting activity isolated from the soil of a ginseng field.

The GenBank/EMBL/DDBJ accession number for the 16S rRNA gene sequence of strain DCY69(T) is JX233806. A Gram-reaction-negative, oxidase- and catalase-positive, non-gliding motile strain, designated strain DCY69(T), was isolated from the soil of a ginseng field in the Republic of Korea. Colonies of strain DCY69(T) were circular, 0.5-1.5 mm diameter, yellow, and convex on an R2A agar plate after 2 days. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain DCY69(T) belonged to the genus Flavobacterium with 90.5-98.3% gene sequence similarity. The major predominant quinone was MK-6. The major cellular fatty acids were iso-C15:0, iso-C17:0 3-OH, iso-C15:0 3-OH and summed feature 3 (containing C16:1ω7c and/or C16:1ω6c). The major polar lipids were phosphatidylethanolamine, one unidentified aminolipid and unidentified polar lipids (L1, L2). The genomic DNA G+C content of strain DCY69(T) was 35.0mol%. The strain DCY69(T) transformed ginsenoside Rb1 into Rd and F2. Based on the polyphasic taxonomic data, strain DCY69(T) is considered to represent a novel species of the genus Flavobacterium, for which the name Flavobacterium panaciterrae sp. nov. is proposed. The type strain is DCY69(T)(= KCTC 32392(T) = JCM 19161(T)), isolated from the soil of a ginseng field in the Republic of Korea.

Flavobacterium ginsengisoli sp. nov., isolated from soil of a ginseng field.

A novel bacterial strain, designated DCY54(T), was isolated from a field cultivated with ginseng in Yongin, Republic of Korea. Cells were Gram-reaction-negative, yellow-pigmented, rod-shaped, non-spore-forming, and strictly aerobic. They were motile by gliding and produced flexirubin-type pigments. Growth occurred optimally at 25-30 °C, at pH 5.0-7.0 and in the presence of 0-1 % NaCl. The 16S rRNA sequence analysis demonstrated that strain DCY54(T) was most closely related to Flavobacterium defluvii EMB117(T) (96.9 %). The only isoprenoid quinone of strain DCY 54(T) was menaquinone-6 (MK-6) and the major polar lipids were phosphatidylethanolamine, one unidentified aminolipid and one unidentified lipid. The major cellular fatty acids (>15 %) were iso-C15 : 0, summed feature 3 (comprising C16 : 1ω7c and/or iso-C15 : 0 2-OH) and C16 : 0. The DNA G+C content was 33.3 mol%. Phylogenetic inference and phenotypic data supported affiliation of strain DCY54(T) to the genus Flavobacterium. Several physiological and biochemical tests differentiated strain DCY54(T) from the species of the genus Flavobacterium with validly published names. On the basis of data from a polyphasic study, strain DCY54(T) represents a novel species of the genus Flavobacterium for which the name Flavobacterium ginsengisoli sp. nov. is proposed. The type strain is DCY54(T) ( = KCTC 23318(T) = JCM 17336(T)).

Bacillus ginsengisoli sp. nov., isolated from soil of a ginseng field.

A novel bacterial strain DCY53(T) was isolated from a soil sample from a ginseng field and was characterized using a polyphasic approach. Cells were Gram-reaction-positive, rod-shaped, endospore-forming and motile with flagella. The strain was aerobic, catalase- and oxidase-positive, optimum growth temperature and pH were 30-37 °C and 6.0-7.5, respectively. On the basis of 16S rRNA gene sequence analysis, strain DCY53(T) was shown to belong to the genus Bacillus and the closest phylogenetic relatives were Bacillus pocheonensis KCTC 13943(T) (98.3 %), Bacillus bataviensis LMG 21833(T) (98.0 %), Bacillus soli LMG 21838(T) (97.9 %), Bacillus drentensis LMG 21831(T) (97.8 %), Bacillus niacini DSM 2923(T) (97.8 %), Bacillus novalis LMG 21837(T) (97.7 %), Bacillus vireti LMG 21834(T) (97.6 %) and Bacillus fumarioli LMG 17489(T) (97.3 %). The DNA G+C content was 43.6 mol% and the predominant respiratory quinone was MK-7. The major fatty acids were iso-C14 : 0, iso-C15 : 0, iso-C16 : 0 and anteiso-C15 : 0. The DNA-DNA relatedness with closest relatives was below 55 %. The results of the genotypic analysis in combination with chemotaxonomic and physiological data demonstrated that DCY53(T) represented a novel species within the genus Bacillus, for which we propose the name Bacillus ginsengisoli. The type strain is DCY53(T) ( = KCTC 13945(T) = JCM 17335(T)).

Pedobacter ginsengiterrae sp. nov., isolated from soil of a ginseng field.

A Gram-stain-negative, oxidase- and catalase-positive bacterial strain that was motile by gliding and produced a pink pigment, designated DCY49(T), was isolated from soil of a ginseng field in a mountainous region of Chungbuk province, South Korea. 16S rRNA gene sequence analysis revealed that strain DCY49(T) belonged to the genus Pedobacter (93.0-96.3 % similarity). Strain DCY49(T) contained MK-7 as the predominant menaquinone. The major fatty acids were summed feature 3 (containing C16 : 1ω7c, C16 : 1ω6c and/or iso-C15 : 0 2-OH), iso-C15 : 0, iso-C17 : 0 3-OH and C16 : 0, and the main polar lipid was phosphatidylethanolamine. The G+C content of the genomic DNA of strain DCY49(T) was 40.5 mol%. Strain DCY49(T) differed from related Pedobacter species by a number of phenotypic characteristics. On the basis of data from the present polyphasic study, strain DCY49(T) is described as representing a novel species of the genus Pedobacter, for which the name Pedobacter ginsengiterrae sp. nov. is proposed. The type strain is DCY49(T) ( = KCTC 23317(T) = JCM 17338(T)).