Combined Effects Methylation of FHIT, RASSF1A and RARβ Genes on Non-Small Cell Lung Cancer in the Chinese Population

Abstract

Epigenetic modifications of tumour suppressor genes are involved in all kinds of human cancer. Aberrant promoter methylation is also considered to play an essential role in development of lung cancer, but the pathogenesis remains unclear.We collected the data of 112 subjects, including 56 diagnosed patients with lung cancer and 56 controls without cancer. Methylation of the FHIT, RASSF1A and RAR-β genes in DNA from all samples and the corresponding gene methylation status were assessed using the methylation-specific polymerase chain reaction (PCR, MSP). The results showed that the total frequency of separate gene methylation was significantly higher in lung cancer compared with controls (33.9-85.7 vs 0 %) (p<0.01).Similar outcomes were obtained from the aberrant methylation of combinations of any two or three genes (p<0.01). There was a tendency that the frequency of combinations of any two or three genes was higher in stageⅠ+Ⅱ than that in stage Ⅲ+Ⅳ with lung cancer. However, no significant difference was found across various clinical stages and clinic pathological gradings of lung cancer (p>0.05).These observations suggest that there is a significant association of promoter methylation of individual genes with lung cancer risk, and that aberrant methylation of combination of any two or three genes may be associated with clinical stage in lung cancer patients and involved in the initiation of lung cancer tumorigenesis. Methylation of FHIT, RASSF1A and RARβ genes may be related to progression of lung oncogenesis.

Aberrant Methylation of RASSF1A gene Contribute to the Risk of Renal Cell Carcinoma: a Meta-Analysis

“…In the past few decades, more and more evidences showed that aberrant DNA methylation, a typical epigenetic modification, had been observed and regarded as a common mechanism leading to inactivation of TSG in cancers (Cancer Genome Atlas Research, 2013;Asiaf et al, 2014;Fang et al, 2014;Li et al, 2014). However, in the previous studies, methylation frequency of RASSF1A gene had been examined only in limited numbers of kidney tumors.…”

Association between Retinoicacid receptor-βhypermethylation and NSCLC risk: a meta-analysis and literature review

“…A number of studies detected and compared the different rate of RARβ hypermethylation; however, the results were contradictory due to limited number of patients from AC and SCC [36–37]. The combining estimates of the odds ratio from 8 publication having 456 SCC and 567 AC is OR = 0.68, 95% CI = 0.52-0.89, p = 0.005, which shows the rate of RARβ hypermethylation was higher in AC than in SCC.…”

Association of Methylation of the RAR-β Gene with Cigarette Smoking in Non-Small Cell Lung Cancer with Southern-central Chinese Population

“…A number of reports had proven that methylation of the RAR-β promoter affected numerous tumor-suppressing genes, which were subsequently silent and not expressed (Li et al, 2014). Other researches had indicated the abnormal methylation of RAR-β was associated with early pathogenesis of lung cancer, induced by correlative environmental factor exposure (Maruyama et al, 2002;Lokk et al, 2012;Shaw et al, 2006;Jin et al, 2009;Zhao et al, 2012).…”

“…The primer sequences (Maruyama et al, 2002;Li et al, 2014), designed to amplify specifically methylated (M) or unmethylated (U) forms of the RAR-β promoter were: M1 (forward) 5'-TCGAGAACGCGAGCGATTC G-3'; M2 (reverse) 5'-GACCAATCCAACCGA AACGA-3'; U1 (forward) 5'-TTGAGAATGTG AGTGATTTGA-3'; U2 (reverse) 5'-AACCAAT CCAACCAAAACAA-3'. The PCR mixture contained 12.5μl TaqMix (Dongsheng, Biotech), 2μl of bisulfitemodified DNA, 1μl 10 pM each primer and 8.5 μl sterile water.…”