Annals of Oncology Advance Access published online on February 23, 2006
Annals of Oncology, doi:10.1093/annonc/mdl018
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1 Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
* To whom correspondence should be addressed. Background: To investigate the clinicopathological significance of promoter methylation of the helicase-like transcription factor (HLTF) in primary gastric cancer. Patients and methods: Two-hundred fifty six patients participated in this study. Methylation status of HLTF gene was evaluated in fresh-frozen tissues by the methylation-specific polymerase chain reaction. All statistical analyses were two-sided, with a 5% type I error rate. Results: Aberrant methylation of HLTF was found in 98 (38%) of 256 gastric cancer patients. HLTF methylation was significantly associated with a family history in the early stages of gastric cancer, regardless of histologic types. In intestinal-type cases, HLTF methylation occurred in 15 (56%) of 27 patients with family histories, and in 26 (31%) of 85 patients without family histories (P = 0.02). In diffuse-type cases, patients with family histories were also found to exhibit a higher prevalence of HLTF methylation than those without family histories (61% vs. 34%; P = 0.009). HLTF methylation in both of the histologic types occurred in about 70-90% of the early stage cases in which the patient had a family history and in 15-30% of cases in which the patient did not have a family history. In our multivariate logistic regression analysis, the stage 1-2 cases with family histories were determined to carry a higher risk of HLTF methylation than did the stage 3-4 cases without family histories in both the intestinal-type (OR = 6.01, 95% CI = 1.20-30.01, P = 0.02) and the diffuse-type cancers (OR = 8.25, 95% CI = 1.67-40.86, P = 0.009). Conclusions: These results suggest that HLTF methylation may play a crucial role in the early stages of gastric carcinogenesis in patients with family histories and may be a valuable susceptible marker for the risk of gastric cancer in individuals with family histories.
Received October 9, 2005
Revised January 1, 2006
Accepted January 9, 2006
original article
Promoter methylation of helicase-like transcription factor is associated with the early stages of gastric cancer with family history
J. J. Kim 1,
S. W. Chung 1,
J. H. Kim 1,
J. W. Kim 2,
J. S. Oh 3,
S. Kim 4,
S. Y. Song 5,
J. Park 6,
and
D-H. Kim 6 *
2 Seoul Science High School, Korea
3 Center for Genome Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Korea
4 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
5 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
6 Center for Genome Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Korea; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea
D-H. Kim, E-mail: dukhwan.kim{at}samsung.com
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