Matsuda T.,Environmental Quality Management |
Tao H.,Hamamatsu University School of Medicine |
Goto M.,Hamamatsu University School of Medicine |
Yamada H.,Hamamatsu University School of Medicine |
And 14 more authors.
Carcinogenesis | Year: 2013
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, butanone-etheno-2'-deoxycytidine (BεdC), butanone-etheno-2'-deoxy-5-methylcytidine, butanone-etheno-2'-deoxyadenosine (BεdA), heptanone-etheno-2'-deoxycytidine, heptanone-etheno-2'-deoxyadenosine (HεdA) and heptanone-etheno- 2'-deoxyguanosine] were identified in a total of 22 gastric mucosa samples. The levels of these adducts ranged from 0 to 30 000 per 109 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 these observations warrant further investigation in the context of the significance of DNA adducts in human gastric carcinogenesis. © The Author 2012. Published by Oxford University Press. All rights reserved. Source
Zhu M.,Nanjing Medical University |
Chen X.,Nanjing Medical University |
Zhang H.,Nanjing Medical University |
Xiao N.,Lujiang People Hospital |
And 6 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2011
Background: 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. Methods: 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). Results: 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. Conclusions: 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. Source
Liu X.,Nanjing University |
Liu X.,Jiangsu Key Laboratory of Molecular Medicine |
Xiao N.,Lujiang People Hospital |
Guo W.,Nanjing University |
And 17 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2011
Purpose: 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. Methods: 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. Results: 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. Conclusions: 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. © 2011 Springer-Verlag. Source