Journal Article

Relationship between <i>CDX2</i> gene methylation and dietary factors in gastric cancer patients

Yasuhito Yuasa, Hiromi Nagasaki, Yoshimitsu Akiyama, Hidekazu Sakai, Tomoko Nakajima, Yasuo Ohkura, Touichirou Takizawa, Morio Koike, Masao Tani, Takehisa Iwai, Kenichi Sugihara, Kazue Imai and Kei Nakachi

in Carcinogenesis

Volume 26, issue 1, pages 193-200
Published in print January 2005 | ISSN: 0143-3334
Published online January 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh304
Relationship between CDX2 gene methylation and dietary factors in gastric cancer patients

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Epigenetic gene silencing through DNA methylation is one of the important steps in the mechanism underlying tumorigenesis, including in the stomach. Past lifestyle factors of cancer patients, such as intake of vegetables, are very important in affecting gastric carcinogenesis. However, the relationship between DNA methylation and past dietary habits in cancer patients remains largely unknown. The CDX2 homeobox transcription factor plays a key role in intestinal development, but CDX2 is also expressed in most of the intestinal metaplasia and part of the carcinomas of the stomach. We analyzed the methylation status of the CDX2 5′ CpG island in gastric cancer cell lines by methylation-specific PCR (MSP), and then CDX2 mRNA was found to be activated after 5-aza-2′-deoxycytidine treatment of the methylation-positive cells. We further examined the methylation status of CDX2 in primary gastric carcinomas by MSP and compared it with the past lifestyle of the patients, including dietary habits. Methylation of CDX2 was found in 20 (34.5%) of the 58 male patients and one (6.7%) of the 15 female patients. Since the methylation frequency was low in the female patients, the analysis was performed only on the male cases. CDX2 methylation was correlated with the decreased intake of green tea and cruciferous vegetables, and also with full or overeating habits. These findings are consistent with epidemiological observations on gastric cancer. We also analyzed the methylation status of p16/INK4a and hMLH1, but their frequencies were not associated with dietary factors or other lifestyle factors. Thus, diet could be an important factor determining the methylation status of genes such as CDX2 and the resultant aberrant expression of genes involved in carcinogenesis.

Keywords: MSP, methylation-specific PCR; RT–PCR, reverse transcription–polymerase chain reaction

Journal Article.  5206 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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