Carcinogenesis Advance Access published online on October 21, 2004
Carcinogenesis, doi:10.1093/carcin/bgh304
© 2004 by Oxford University Press
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1 Department of Molecular Oncology, Tokyo Medical and Dental University, Tokyo, Japan
* To whom correspondence should be addressed. Epigenetic gene silencing through DNA methylation is one of the important steps in the mechanism underlying tumorigenesis, including of the stomach. Past lifestyle factors of cancer patients, such as intake of vegetables, are very important to affect 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 intestinal metaplasia and a part of 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 1 (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 nor 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.
Revised September 5, 2004
Accepted September 29, 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Relationship between CDX2 gene methylation and dietary factors in gastric cancer patients
2 Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Tochigi, Japan
3 Department of Pathology, Tokyo Medical and Dental University, Tokyo, Japan
4 Department of Surgery, Tokyo Medical and Dental University, Tokyo, Japan
5 Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan
Yasuhito Yuasa, E-mail: yuasa.monc{at}tmd.ac.jp
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