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  • American Association for Cancer Research (AACR)  (2)
  • Nakajima, Takeshi  (2)
  • 2005-2009  (2)
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  • American Association for Cancer Research (AACR)  (2)
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  • 2005-2009  (2)
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  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2006
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 15, No. 11 ( 2006-11-01), p. 2317-2321
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 15, No. 11 ( 2006-11-01), p. 2317-2321
    Abstract: Background: Helicobacter pylori infection potently induces methylation of CpG islands in gastric mucosae, which is considered to decrease to a certain level after active H. pylori infection discontinues. Noncancerous gastric mucosae of H. pylori–negative cases with a gastric cancer had higher methylation levels than those of H. pylori–negative healthy individuals. Here, using cases with multiple gastric cancers, we analyzed whether the higher methylation levels correlated with the higher risk of gastric cancers. Methods: Twenty-six healthy volunteers (HV), 30 cases with a single well-differentiated gastric cancer (S cases), and 32 cases with multiple well-differentiated gastric cancers (M cases) were recruited. H. pylori infection status was analyzed by the culture method. Methylation levels were quantified by real-time methylation-specific PCR of seven CpG islands. Results: In H. pylori–negative individuals, significant increasing trends were present in the order of HV, S cases, and M cases for FLNc and HAND1 methylation levels (P & lt; 0.01, Spearman's rank-order test). Furthermore, the FLNc methylation level of M cases was significantly higher than that of S cases (P & lt; 0.01, t test). Even adjusted by the extent of gastric atrophy, the FLNc methylation level retained a significant increasing trend (P = 0.03). In contrast, methylation levels in H. pylori–positive individuals were increased to various degrees in all the three groups. Conclusions: In H. pylori–negative individuals, methylation levels in gastric mucosae significantly increased in cases with a single gastric cancer and more in cases with multiple gastric cancers. Quantitative analysis of methylation levels is a promising risk marker for gastric cancers. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2317–21)
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2006
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 2
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 12, No. 3 ( 2006-02-01), p. 989-995
    Abstract: Introduction: Risk prediction of gastric cancers is important to implement appropriate screening procedures. Although aberrant DNA methylation is deeply involved in gastric carcinogenesis, its induction by Helicobacter pylori, a strong gastric carcinogen, is unclear. Here, we analyzed the effect of H. pylori infection on the quantity of methylated DNA molecules in noncancerous gastric mucosae and examined its association with gastric cancer risk. Experimental Design: Gastric mucosae were collected from 154 healthy volunteers (56 H. pylori negative and 98 H. pylori positive) and 72 cases with differentiated-type gastric cancers (29 H. pylori negative and 43 H. pylori positive) by endoscopy. The numbers of DNA molecules methylated and unmethylated for eight regions of seven CpG islands (CGI) were quantified by quantitative PCR after bisulfite modification, and fractions of methylated molecules (methylation levels) were calculated. Results: Among healthy volunteers, methylation levels of all the eight regions were 5.4- to 303-fold higher in H. pylori positives than in H. pylori negatives (P & lt; 0.0001). Methylation levels of the LOX, HAND1, and THBD promoter CGIs and p41ARC exonic CGI were as high as 7.4% or more in H. pylori–positive individuals. Among H. pylori–negative individuals, methylation levels of all the eight regions were 2.2- to 32-fold higher in gastric cancer cases than in age-matched healthy volunteers (P ≤ 0.01). Among H. pylori–positive individuals, methylation levels were highly variable, and that of only HAND1 was significantly increased in gastric cancer cases (1.4-fold, P = 0.02). Conclusions: It was indicated that H. pylori infection potently induces methylation of CGIs to various degrees. Methylation levels of specific CGIs seemed to reflect gastric cancer risk in H. pylori–negative individuals.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2006
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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