Higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancers.
BACKGROUND
Helicobacter pylori infection potently induces methylation of CpG islands in gastric mucosae, which is considered to decrease to a certain level after active H. pylori infection discontinues. Noncancerous gastric mucosae of H. pylori-negative cases with a gastric cancer had higher methylation levels than those of H. pylori-negative healthy individuals. Here, using cases with multiple gastric cancers, we analyzed whether the higher methylation levels correlated with the higher risk of gastric cancers.


METHODS
Twenty-six healthy volunteers (HV), 30 cases with a single well-differentiated gastric cancer (S cases), and 32 cases with multiple well-differentiated gastric cancers (M cases) were recruited. H. pylori infection status was analyzed by the culture method. Methylation levels were quantified by real-time methylation-specific PCR of seven CpG islands.


RESULTS
In H. pylori-negative individuals, significant increasing trends were present in the order of HV, S cases, and M cases for FLNc and HAND1 methylation levels (P < 0.01, Spearman's rank-order test). Furthermore, the FLNc methylation level of M cases was significantly higher than that of S cases (P < 0.01, t test). Even adjusted by the extent of gastric atrophy, the FLNc methylation level retained a significant increasing trend (P = 0.03). In contrast, methylation levels in H. pylori-positive individuals were increased to various degrees in all the three groups.


CONCLUSIONS
In H. pylori-negative individuals, methylation levels in gastric mucosae significantly increased in cases with a single gastric cancer and more in cases with multiple gastric cancers. Quantitative analysis of methylation levels is a promising risk marker for gastric cancers.
Nakajima
Takeshi
T
Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.
Maekita
Takao
T
Oda
Ichiro
I
Gotoda
Takuji
T
Yamamoto
Seiichiro
S
Umemura
Satoshi
S
Ichinose
Masao
M
Sugimura
Takashi
T
Ushijima
Toshikazu
T
Saito
Daizo
D
D000368:Aged; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D005838:Genotype; D016480:Helicobacter pylori / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D013274:Stomach Neoplasms / Q000473:pathology*