Annals of Oncology Advance Access originally published online on February 23, 2006
Annals of Oncology 2006 17(4):657-662; doi:10.1093/annonc/mdl018
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© 2006 European Society for Medical Oncology
Promoter methylation of helicase-like transcription factor is associated with the early stages of gastric cancer with family history
1 Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine; 2 Seoul Science High School; 3 Center for Genome Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine; 4 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine; 5 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine; 6 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea
* Correspondence to: Dr D-H. Kim, Center for Genome Research, Samsung Biomedical Research Institute, Rm B155, #50 Ilwon-dong, Kangnam-Ku, Seoul, Korea, 135–710. Tel: +82 (02) 3410–3632; Fax: +82 (02) 3410–3649; E-mail: dukhwan.kim{at}samsung.com
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.
Key words: HLTF, methylation, gastric cancer, family history, early stage
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