Association between cyclin D1 polymorphism with CpG island promoter methylation status of tumor suppressor genes in gastric cancer

Tomomitsu Tahara, Tomoyuki Shibata, Masakatsu Nakamura, Hiromi Yamashita, Daisuke Yoshioka, Masaaki Okubo, Joh Yonemura, Yoshiteru Maeda, Naoko Maruyama, Toshiaki Kamano, Yoshio Kamiya, Hiroshi Fujita, Yoshihito Nakagawa, Mitsuo Nagasaka, Masami Iwata, Ichiro Hirata, Tomiyasu Arisawa

研究成果: Article

6 引用 (Scopus)

抄録

Background: CpG island hypermethylation of tumor suppressor genes is highly involved in gastric carcinogenesis, and enhanced cell proliferation could accelerate this process. Cyclin D1 regulates cell cycle function and may play a role in methylation-related carcinogenesis. Aims: We investigated the association between Cyclin D1 gene G870A polymorphism and the methylation status of tumor suppressor genes in gastric cancer. Methods: Polymorphisms at G870A in the Cyclin D1 gene were genotyped, and methylation status of the p14, p16, DAP-kinase, and CDH1 genes were determined by methylation-specific-polymerase chain reaction in 139 gastric cancer tissues. CIHM high was defined as three or more methylated CpG islands. Results: Although no association was found between methylation status and different stages and Lauren's subtypes, patients with CIHM of DAP-kinase showed significantly worse survival than those without (p = 0.017). In addition, the number of methylated sites was also associated with survival curves (p = 0.0397). The 870G carrier a significantly lower prevalence of CIHM high compared to the AA genotype in advanced-stage gastric cancer (adjusted OR = 0.32, p = 0.047). A weak correlation between the same genotypes and CIHM of p14 were found in the same subtype (adjusted OR = 0.32, p = 0.052). The mean methylation number was significantly lower in G carriers than in AA genotypes in advanced-stage gastric cancer (p = 0.017). Conclusions: Genetic polymorphism of CCND1 is associated with CIHM status in gastric cancer, especially in the advanced stage, but is independent of clinico-pathological features.

元の言語English
ページ(範囲)3449-3457
ページ数9
ジャーナルDigestive Diseases and Sciences
55
発行部数12
DOI
出版物ステータスPublished - 01-12-2010

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CpG Islands
Cyclin D1
Tumor Suppressor Genes
Methylation
Stomach Neoplasms
Death-Associated Protein Kinases
bcl-1 Genes
Genotype
Carcinogenesis
Survival
Genetic Polymorphisms
Stomach
Cell Cycle
Cell Proliferation
Polymerase Chain Reaction
Genes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Gastroenterology

これを引用

Tahara, Tomomitsu ; Shibata, Tomoyuki ; Nakamura, Masakatsu ; Yamashita, Hiromi ; Yoshioka, Daisuke ; Okubo, Masaaki ; Yonemura, Joh ; Maeda, Yoshiteru ; Maruyama, Naoko ; Kamano, Toshiaki ; Kamiya, Yoshio ; Fujita, Hiroshi ; Nakagawa, Yoshihito ; Nagasaka, Mitsuo ; Iwata, Masami ; Hirata, Ichiro ; Arisawa, Tomiyasu. / Association between cyclin D1 polymorphism with CpG island promoter methylation status of tumor suppressor genes in gastric cancer. :: Digestive Diseases and Sciences. 2010 ; 巻 55, 番号 12. pp. 3449-3457.
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title = "Association between cyclin D1 polymorphism with CpG island promoter methylation status of tumor suppressor genes in gastric cancer",
abstract = "Background: CpG island hypermethylation of tumor suppressor genes is highly involved in gastric carcinogenesis, and enhanced cell proliferation could accelerate this process. Cyclin D1 regulates cell cycle function and may play a role in methylation-related carcinogenesis. Aims: We investigated the association between Cyclin D1 gene G870A polymorphism and the methylation status of tumor suppressor genes in gastric cancer. Methods: Polymorphisms at G870A in the Cyclin D1 gene were genotyped, and methylation status of the p14, p16, DAP-kinase, and CDH1 genes were determined by methylation-specific-polymerase chain reaction in 139 gastric cancer tissues. CIHM high was defined as three or more methylated CpG islands. Results: Although no association was found between methylation status and different stages and Lauren's subtypes, patients with CIHM of DAP-kinase showed significantly worse survival than those without (p = 0.017). In addition, the number of methylated sites was also associated with survival curves (p = 0.0397). The 870G carrier a significantly lower prevalence of CIHM high compared to the AA genotype in advanced-stage gastric cancer (adjusted OR = 0.32, p = 0.047). A weak correlation between the same genotypes and CIHM of p14 were found in the same subtype (adjusted OR = 0.32, p = 0.052). The mean methylation number was significantly lower in G carriers than in AA genotypes in advanced-stage gastric cancer (p = 0.017). Conclusions: Genetic polymorphism of CCND1 is associated with CIHM status in gastric cancer, especially in the advanced stage, but is independent of clinico-pathological features.",
author = "Tomomitsu Tahara and Tomoyuki Shibata and Masakatsu Nakamura and Hiromi Yamashita and Daisuke Yoshioka and Masaaki Okubo and Joh Yonemura and Yoshiteru Maeda and Naoko Maruyama and Toshiaki Kamano and Yoshio Kamiya and Hiroshi Fujita and Yoshihito Nakagawa and Mitsuo Nagasaka and Masami Iwata and Ichiro Hirata and Tomiyasu Arisawa",
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Tahara, T, Shibata, T, Nakamura, M, Yamashita, H, Yoshioka, D, Okubo, M, Yonemura, J, Maeda, Y, Maruyama, N, Kamano, T, Kamiya, Y, Fujita, H, Nakagawa, Y, Nagasaka, M, Iwata, M, Hirata, I & Arisawa, T 2010, 'Association between cyclin D1 polymorphism with CpG island promoter methylation status of tumor suppressor genes in gastric cancer', Digestive Diseases and Sciences, 巻. 55, 番号 12, pp. 3449-3457. https://doi.org/10.1007/s10620-010-1206-5

Association between cyclin D1 polymorphism with CpG island promoter methylation status of tumor suppressor genes in gastric cancer. / Tahara, Tomomitsu; Shibata, Tomoyuki; Nakamura, Masakatsu; Yamashita, Hiromi; Yoshioka, Daisuke; Okubo, Masaaki; Yonemura, Joh; Maeda, Yoshiteru; Maruyama, Naoko; Kamano, Toshiaki; Kamiya, Yoshio; Fujita, Hiroshi; Nakagawa, Yoshihito; Nagasaka, Mitsuo; Iwata, Masami; Hirata, Ichiro; Arisawa, Tomiyasu.

:: Digestive Diseases and Sciences, 巻 55, 番号 12, 01.12.2010, p. 3449-3457.

研究成果: Article

TY - JOUR

T1 - Association between cyclin D1 polymorphism with CpG island promoter methylation status of tumor suppressor genes in gastric cancer

AU - Tahara, Tomomitsu

AU - Shibata, Tomoyuki

AU - Nakamura, Masakatsu

AU - Yamashita, Hiromi

AU - Yoshioka, Daisuke

AU - Okubo, Masaaki

AU - Yonemura, Joh

AU - Maeda, Yoshiteru

AU - Maruyama, Naoko

AU - Kamano, Toshiaki

AU - Kamiya, Yoshio

AU - Fujita, Hiroshi

AU - Nakagawa, Yoshihito

AU - Nagasaka, Mitsuo

AU - Iwata, Masami

AU - Hirata, Ichiro

AU - Arisawa, Tomiyasu

PY - 2010/12/1

Y1 - 2010/12/1

N2 - Background: CpG island hypermethylation of tumor suppressor genes is highly involved in gastric carcinogenesis, and enhanced cell proliferation could accelerate this process. Cyclin D1 regulates cell cycle function and may play a role in methylation-related carcinogenesis. Aims: We investigated the association between Cyclin D1 gene G870A polymorphism and the methylation status of tumor suppressor genes in gastric cancer. Methods: Polymorphisms at G870A in the Cyclin D1 gene were genotyped, and methylation status of the p14, p16, DAP-kinase, and CDH1 genes were determined by methylation-specific-polymerase chain reaction in 139 gastric cancer tissues. CIHM high was defined as three or more methylated CpG islands. Results: Although no association was found between methylation status and different stages and Lauren's subtypes, patients with CIHM of DAP-kinase showed significantly worse survival than those without (p = 0.017). In addition, the number of methylated sites was also associated with survival curves (p = 0.0397). The 870G carrier a significantly lower prevalence of CIHM high compared to the AA genotype in advanced-stage gastric cancer (adjusted OR = 0.32, p = 0.047). A weak correlation between the same genotypes and CIHM of p14 were found in the same subtype (adjusted OR = 0.32, p = 0.052). The mean methylation number was significantly lower in G carriers than in AA genotypes in advanced-stage gastric cancer (p = 0.017). Conclusions: Genetic polymorphism of CCND1 is associated with CIHM status in gastric cancer, especially in the advanced stage, but is independent of clinico-pathological features.

AB - Background: CpG island hypermethylation of tumor suppressor genes is highly involved in gastric carcinogenesis, and enhanced cell proliferation could accelerate this process. Cyclin D1 regulates cell cycle function and may play a role in methylation-related carcinogenesis. Aims: We investigated the association between Cyclin D1 gene G870A polymorphism and the methylation status of tumor suppressor genes in gastric cancer. Methods: Polymorphisms at G870A in the Cyclin D1 gene were genotyped, and methylation status of the p14, p16, DAP-kinase, and CDH1 genes were determined by methylation-specific-polymerase chain reaction in 139 gastric cancer tissues. CIHM high was defined as three or more methylated CpG islands. Results: Although no association was found between methylation status and different stages and Lauren's subtypes, patients with CIHM of DAP-kinase showed significantly worse survival than those without (p = 0.017). In addition, the number of methylated sites was also associated with survival curves (p = 0.0397). The 870G carrier a significantly lower prevalence of CIHM high compared to the AA genotype in advanced-stage gastric cancer (adjusted OR = 0.32, p = 0.047). A weak correlation between the same genotypes and CIHM of p14 were found in the same subtype (adjusted OR = 0.32, p = 0.052). The mean methylation number was significantly lower in G carriers than in AA genotypes in advanced-stage gastric cancer (p = 0.017). Conclusions: Genetic polymorphism of CCND1 is associated with CIHM status in gastric cancer, especially in the advanced stage, but is independent of clinico-pathological features.

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U2 - 10.1007/s10620-010-1206-5

DO - 10.1007/s10620-010-1206-5

M3 - Article

C2 - 20397048

AN - SCOPUS:78649316677

VL - 55

SP - 3449

EP - 3457

JO - American Journal of Digestive Diseases

JF - American Journal of Digestive Diseases

SN - 0002-9211

IS - 12

ER -