Qiong He

Nanjing Medical University, Nan-ching, Jiangsu Sheng, China

Are you Qiong He?

Claim your profile

Publications (7)19.39 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Gastric cancer (GC) is considered to be one of the leading cancers in East Asians, and mutations in the CDH1 gene and the reduced expression of E-cadherin are the most frequent genetic alterations in gastric cancer. In this paper, we reported two novel germline CDH1 nonsynonymous mutations, c.1296 C>G (N432 K) and c.1297 G>A (D433 N) detected in sporadic Chinese GC patients. RNA splicing analysis was used to evaluate mutations' effects on E-cadherin transcription and exon definition. We revealed that the c.1296 C>G (N432 K) variant can generate the E-cadherin exon9-skipping and may be a disease-causing mutation, while the c.1297 G>A (D433 N) mutation not. Moreover, we demonstrated the E-cadherin 1054del83 transcript is a frequent event in Chinese GC patients.
    Familial Cancer 02/2013; DOI:10.1007/s10689-013-9619-x · 1.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To give a comprehensive report of E-cadherin gene (CDH1) variations in a population at a high risk for gastric cancer (GC). The samples consisted of 178 men and 58 women with a mean age of 62.3 ± 9.4 years and an age range of 30-84 years. A total of 240 cancer-free controls were recruited (mean age of 61.8 ± 10.1 years, age range of 26-82 years). Samples were screened for CDH1 germline mutations by high-resolution melting analysis or directly sequencing. Luciferase reporter assay, RNA splicing assay and bioinformatic analysis were used to evaluate the effect of mutations. Four novel CDH1 sequence alterations were identified in GC patients including a G>T transition 49 bp before the start codon; a three-nucleotide deletion, c.44_46del TGC; one missense mutation, c.604G>A (V202I); and one variation in the intron, c.1320+7A>G. In addition, polymorphism frequencies were observed for CDH1-164delT, -161C>A, -73A>C, c.48+6C>T, c.48+62_48+63delinsCGTGCCCCAGCCC, c.894C>T (A298A), c.1224G>A (A408A), c.1888C>G (L630V), c.2076T>C (A692A), and c.2253C>T (N751N) which is similar to the data reported in http://www.ncbi.nlm.nih.gov/projects/SNP/. RNA splicing analysis suggested that the c.1320+7A>G and c.1224G>A variations did not affect exon splicing ability. Luciferase reporter assay demonstrated that the c.-49T variation might be helpful for E-cadherin transcription, though the increase in transcription activity is limited (only 33%). SIFT score and PolyPhen analysis both demonstrated that the L630V missense mutation probably damages protein function, while the V202I variant does not. This study reveals novel mutations in sporadic GC patients which had been poorly investigated for susceptibility genes.
    World Journal of Gastroenterology 02/2013; 19(6):909-16. DOI:10.3748/wjg.v19.i6.909 · 2.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: DNA adducts are a major cause of DNA mutation and DNA mutation-related diseases, but the simultaneous identification of multiple DNA adducts has been a challenge for a decade. An adductome approach using consecutive liquid chromatography and double mass spectrometry after micrococcal nuclease treatment has paved the way to demonstrations of numerous DNA adducts in a single experiment and is expected to contribute to the comprehensive understanding of overall environmental and endogenous exposures to possible mutagens in individuals. In this report we applied an adductome approach to gastric mucosa samples taken at the time of a gastrectomy for gastric cancer in Lujiang, China, and in Hamamatsu, Japan. Seven lipid peroxidation-related DNA adducts (1,N6-etheno-2'-deoxyadenosine [εdA], butanone-etheno-2'-deoxycytidine [BεdC], butanone-etheno-2'-deoxy-5-methylcytidine [BεmedC], butanone- etheno-2'-deoxyadenosine [BεdA], heptanone-etheno-2'-deoxycytidine [HεdC], heptanone-etheno-2'-deoxyadenosine [HεdA], and heptanone-etheno- 2'-deoxyguanosine [HεεdG]) were identified in a total of 22 gastric mucosa samples. The levels of these adducts ranged from 0 to 30,000 per 10(9)bases. Although the presence of Helicobacter pylori DNA in the mucosa was not related to these adducts level, the levels of BεdC,BεdA, and HεdA were higher in the Japanese gastric mucosa samples. The profiles of these 7 adduct levels among the 21 cases were capable of discriminating between the possible origins (China or Japan) of the gastric mucosa samples. Our report is the first demonstration of lipid peroxidation-related DNA adducts in the human stomach, and the present observations warrant further investigation in the context of the significance of DNA adducts in human gastric carcinogenesis.
    Carcinogenesis 10/2012; 34(1). DOI:10.1093/carcin/bgs327 · 5.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To explore germline hypermethylation of the tumor suppressor genes MLH1, CDH1 and P16(INK4a) in suspected cases of hereditary gastric cancer (GC). A group of 140 Chinese GC patients in whom the primary cancer had developed before the age of 60 or who had a familial history of cancer were screened for germline hypermethylation of the MLH1, CDH1 and P16(INK4a) tumor suppressor genes. Genomic DNA was extracted from peripheral blood leukocytes and modified by sodium bisulfite. The treated DNA was then subjected to bisulfite DNA sequencing for a specific region of the MLH1 promoter. The methylation status of CDH1 or P16(INK4a) was assayed using methylation-specific PCR. Clonal bisulfite allelic sequencing in positive samples was performed to obtain a comprehensive analysis of the CpG island methylation status of these promoter regions. Methylation of the MLH1 gene promoter was detected in the peripheral blood DNA of only 1/140 (0.7%) of the GC patient group. However, this methylation pattern was mosaic rather than the allelic pattern which has previously been reported for MLH1 in hereditary non-polyposis colorectal cancer (HNPCC) patients. We found that 10% of the MLH1 alleles in the peripheral blood DNA of this patient were methylated, consistent with 20% of cells having one methylated allele. No germline promoter methylation of the CDH1 or P16(INK4a) genes was detected. Mosaic germline epimutation of the MLH1 gene is present in suspected hereditary GC patients in China but at a very low level. Germline epimutation of the CDH1 or P16(INK4a) gene is not a frequent event.
    World Journal of Gastroenterology 01/2012; 18(1):70-8. DOI:10.3748/wjg.v18.i1.70 · 2.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Gastric cancer is one of the most common cancers affecting East Asians, and MLH1 could play a critical role during tumorigenesis in this condition. Samples from 236 Chinese patients suffering from gastric cancer were screened for MLH1 germline mutations. Carrier frequencies of the mutations were compared between gastric cancer patients and 240 cancer-free controls. Bioinformatic analysis was used to predict the effect of these mutations on protein function and mRNA splicing. Six MLH1 sequence alterations were identified in gastric cancer patients including two promoter region substitutions, -93G>A and -28A>G, and four missense mutations 649C>T (R217C), 655A>G (I219V), 1151T>A (V384D) and 2101C>A (Q701K). Compared with the MLH1 2101CC genotype, the 2101CA genotype was associated with a risk of gastric cancer (OR = 8.42, 95% CI = 1.04-68.06) in males. Furthermore, the MLH1 2101C>A mutant was predicted by in silico analysis to affect exon splicing ability. Immunohistochemistry of one index patient carrying the MLH1 2101C>A mutation demonstrated a loss of MLH1 protein and normal expression of MSH2 and E-cadherin. No significant differences were demonstrated between cases and controls for the other five MLH1 variants but the data indicated an ethnic difference in the frequency of these variations between Eastern Asians and Western populations. An ethnic-specific MLH1 mutation spectrum occurred in Chinese gastric cancer patients. The MLH1 2101C>A mutation could be a marker for susceptibility to gastric cancer, particularly in males.
    BMC Gastroenterology 12/2011; 11(1):133. DOI:10.1186/1471-230X-11-133 · 2.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The incidence and mortality of gastric and colorectal cancers are among the highest malignant tumors in China. The aim of this study is to investigate whether variations of the human oxoguanine glycosylase 1 (hOGG1) gene are related to the risk of gastric and colorectal cancers in the Chinese population. There were 622 gastric cancer patients, 383 colorectal cancer patients, and 932 healthy controls recruited to screen for variations in the 5'untranslated region (UTR) and to screen for the missense mutation (p.Ser326Cys) in exon7 of the hOGG1 gene using high-resolution melting curve analysis (HRM) and subsequent sequencing. The promoter luciferase activity assay was applied to assess the potential influence of the detected variants on gene function. Four variations, c.-53G>C, c.-45G>A, c.-23A>G, and c.-18G>T, were detected in the 5'-UTR of the hOGG1 gene. The case-control study indicated that the c.-53G/C heterozygous genotype was markedly associated with gastric cancer (P = 0.008, OR = 2.304, 95% CI, 1.258-4.221), but not with colorectal cancer. The clinicopathological association analysis showed that the variant of c.-53G>C in the hOGG1 gene was prevalent in low-differentiation patients (P = 0.012, OR = 3.174, 95% CI: 1.352-7.448). This variant decreased the gene promoter activity by approximately 17.8% (P = 0.041) and exhibited a synergistic effect with the missense mutation p.Ser326Cys of hOGG1 by enhancing susceptibility to gastric cancers. The variant c.-53G>C in the 5'-UTR of the hOGG1 gene is a risk factor for gastric cancer and is potentially associated with low-differentiation degree, but not with colorectal cancer, in the Chinese population.
    Journal of Cancer Research and Clinical Oncology 08/2011; 137(10):1477-85. DOI:10.1007/s00432-011-1022-0 · 3.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A common polymorphism of the AluYb8 insertion in the MUTYH gene (AluYb8MUTYH), which led to the increase of oxidative DNA damage and acceleration of chronic diseases, was previously detected. Considering the relationship between carcinogenesis and oxidative stress, an investigation was held on whether the common variant of the MUTYH gene increases the risk for gastric and breast cancers. The AluYb8MUTYH allele frequencies of 545 breast cancer patients and 762 gastric cancer patients were analyzed and compared with that of the healthy control group using the Chi-square test. The binary logistic regression model was used to examine the association between the polymorphism genotypes and cancer risk. Genomic DNA specimens from the investigated population were tested by polymerase chain reaction in agarose gel electrophoresis. According to the insertion absence or presence of the variant segment, the patterns for the AluYb8MUTYH genotypes were classified as a homozygous of absence/absence (A/A) and presence/presence (P/P) or a heterozygous of absence/presence (A/P). The variant allele frequency (insertion present, P) was inclined to be enhanced in breast cancer patients as compared with the normal female controls (46.8% versus 43.3%), and also, in gastric cancer patients, as compared with the general normal controls (45.1% versus 43.9%). However, a significantly different P allele frequency was only detected between the early-onset breast cancer patients (<55 years old) and their counterpart female controls (46.6% versus 40.9%, p=0.042; OR=1.26, 95% CI, 1.01-1.56), as well as between the early-onset gastric cancer patients and their respective controls (49.2% versus 41.3%, p=0.042; OR, 1.37; 95% CI, 1.02-1.85). Comparisons on the genotypes of AluYb8MUTYH show that this variation of MUTYH has also a significantly higher prevalence in the early-onset cancer patients, either in breast or gastric cancer patients, than that in their counterpart controls. The AluYb8MUTYH allele frequency can be associated with the early-onset breast and gastric cancer in the Chinese population. Probably, there is importance in screening the carriers with the susceptibility alleles to evaluate their risk of breast and gastric cancer for further research.
    Asian Pacific journal of cancer prevention: APJCP 01/2011; 12(6):1451-5. · 2.51 Impact Factor