Promoter methylation of helicase-like transcription factor is associated with the early stages of gastric cancer with family history.
BACKGROUND
To investigate the clinicopathological significance of promoter methylation of the helicase-like transcription factor (HLTF) in primary gastric cancer.


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.
Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, Korea.
J J
JJ
Kim
S W
SW
Chung
J H
JH
Kim
J W
JW
Kim
J S
JS
Oh
S
S
Kim
S Y
SY
Song
J
J
Park
D-H
DH
Kim
D000368:Aged; D001483:Base Sequence; D019175:DNA Methylation; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*
D017931:DNA Primers; D014157:Transcription Factors