CpG island methylator phenotype involving chromosome 3p confers an increased risk of non-small cell lung cancer.
OBJECTIVE
This study aims to explore the association of CpG island methylator phenotype (CIMP) involving tumor suppressor genes on short arm of chromosome 3 (3p) with increased risk of non-small cell lung cancer (NSCLC).


METHODS
In this study, four NSCLC cell lines were cultured, and peripheral blood mononuclear cell (PBMC) specimens from 80 patients with NSCLC and 80 matched controls were collected for 3p-involved CIMP (3pCIMP) analysis. 3pCIMP was referred to as having at least three synchronously methylated genes of 3p per sample. Methylation-specific polymerase chain reaction was performed to examine the methylation status of each gene. DNA demethylation of NSCLC cell lines was achieved through the treatment with 5-aza-deoxycytidine. Logistic regression was used to assess odds ratios and 95% confidence intervals, which were adjusted for gender, age, and smoking status.


RESULTS
Demethylation experiment showed that 3pCIMP status could play an important role in NSCLC cell proliferation. A total of 97.5% of PBMC specimens from NSCLC patients presented promoter methylation of any one of six genes (hOGG1, RAR-B, SEMA3B, RASSF1A, BLU, or FHIT) on 3p. Interestingly, 3pCIMP+ was found in 43.8% of NSCLC PBMC specimens and only in 6.3% of normal PBMC samples. The data suggest that 3pCIMP status is significantly associated with NSCLC and normal PBMC samples (p 0.001). More importantly, the results show that 3pCIMP positive carriers have a 12.8-fold increased risk of NSCLC (adjusted odds ratio, 12.8; 95% confidence interval, 4.38 -37.4, p 0.001) in Chinese population.


CONCLUSIONS
This is the first evidence of an association between PBMC 3pCIMP and risk for NSCLC.
Soochow University Laboratory of Cancer Molecular Genetics, School of Basic Medicine and Biological Sciences, Medical College of Soochow University, Suzhou, People's Republic of China.
Zeyi
Z
Liu
Wenwen
W
Li
Zhe
Z
Lei
Jun
J
Zhao
Xiao-Feng
XF
Chen
Rengyun
R
Liu
Xiaobei
X
Peng
Zhi-hao
ZH
Wu
Jun
J
Chen
Hongyu
H
Liu
Qing-Hua
QH
Zhou
Hong-Tao
HT
Zhang
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002893:Chromosomes, Human, Pair 3; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012306:Risk