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Association of RASSF1A Promoter Methylation with Lung Cancer Risk: a Meta-analysis

  • Huang, Ying-Ze (Lab of Molecular Genetics of Aging and Tumor, Medical Faculty, Kunming University of Science and Technology) ;
  • Wu, Wei (Lab of Molecular Genetics of Aging and Tumor, Medical Faculty, Kunming University of Science and Technology) ;
  • Wu, Kun (Lab of Molecular Genetics of Aging and Tumor, Medical Faculty, Kunming University of Science and Technology) ;
  • Xu, Xiao-Ning (Lab of Molecular Genetics of Aging and Tumor, Medical Faculty, Kunming University of Science and Technology) ;
  • Tang, Wen-Ru (Lab of Molecular Genetics of Aging and Tumor, Medical Faculty, Kunming University of Science and Technology)
  • Published : 2015.01.06

Abstract

RASSF1A, regarded as a candidate tumor suppressor, is frequently silenced and inactivated by methylation of its promoter region in many human tumors. However, the association between RASSF1A promoter methylation and lung cancer risk remains unclear. To provide a more reliable estimate we conducted a meta-analysis of cohort studies to evaluate the potential role of RASSF1A promoter methylation in lung carcinogenesis. Relevant studies were identified by searches of PubMed, Web of Science, ProQest and Medline databases using the following key words: 'lung cancer or lung neoplasm or lung carcinoma', 'RASSF1A methylation' or 'RASSF1A hypermethylation'. According to the selection standard, 15 articles were identified and analysised by STATA 12.0 software. Combined odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association between RASSF1A promoter methylation and lung cancer risk. A chi-square-based Q test and sensitivity analyses were performed to test between-study heterogeneity and the contributions of single studies to the final results, respectively. Funnel plots were carried out to evaluate publication bias. Overall, a significant relationship between RASSF1A promoter methylation and lung cancer risk (OR, 16.12; 95%CI, 11.40-22.81; p<0.001) with no between-study heterogeneity. In subgroup analyses, increased risk of RASSF1A methylation in cases than controls was found for the NSCLC group (OR, 13.66, 95%CI, 9.529-19.57) and in the SCLC group (OR, 314.85, 95%CI, 48.93-2026.2).

Keywords

RASSF1A;lung cancer;methylation;NSCLC and SCLC

Acknowledgement

Supported by : Higher Education of China

References

  1. Amin KS, Banerjee PP (2012). The cellular functions of RASSF1A and its inactivation in prostate cancer. J Carcinog, 11, 3. https://doi.org/10.4103/1477-3163.93000
  2. Baylin SB (2005). DNA methylation and gene silencing in cancer. Nat Clin Pract Oncol, 2, 4-11.
  3. Brock MV HC, Ota-Machida E, Han Y, et al (2008). DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med, 13, 1118-28.
  4. Burbee DG, Forgacs E, Zochbauer-Muller S, et al (2001). Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. J Natl Cancer Inst, 93, 691-9. https://doi.org/10.1093/jnci/93.9.691
  5. Chen H, Suzuki M, Nakamura Y, et al (2006). Aberrant methylation of RASGRF2 and RASSF1A in human non-small cell lung cancer. Oncol Rep, 15, 1281-5.
  6. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88. https://doi.org/10.1016/0197-2456(86)90046-2
  7. Dickersin K, Berlin JA (1992). Meta-analysis: state-of-thescience. Epidemiol Rev, 14, 154-76.
  8. Egger M, Davey Smith G, Schneider M, Minder C. (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629-34 https://doi.org/10.1136/bmj.315.7109.629
  9. Fischer JR, Ohnmacht U, Rieger N, et al (2007). Prognostic significance of RASSF1A promoter methylation on survival of non-small cell lung cancer patients treated with gemcitabine. Lung Cancer, 56, 115-23. https://doi.org/10.1016/j.lungcan.2006.11.016
  10. Grote HJ, Schmiemann V, Geddert H, et al (2006). Methylation of RAS association domain family protein 1A as a biomarker of lung cancer. Cancer Cytopathology, 108, 129-34.
  11. Helmbold P, Lahtz C, Herpel E, et al (2009). Frequent hypermethylation of RASSF1A tumour suppressor gene promoter and presence of Merkel cell polyomavirus in small cell lung cancer. Eur J Cancer, 45, 2207-11. https://doi.org/10.1016/j.ejca.2009.04.038
  12. Hesson LB, Cooper WN, Latif F (2007). The role of RASSF1A methylation in cancer. Dis Markers, 23, 73-87. https://doi.org/10.1155/2007/291538
  13. Agathanggelou A, Bieche I, Ahmed-Choudhury J, et al (2003). Identification of novel gene expression targets for the Ras association domain family 1 (RASSF1A) tumor suppressor gene in non-small cell lung cancer and neuroblastoma. Cancer Res, 63, 5344-51.
  14. Agathanggelou A, Honorio S, Macartney DP, et al (2001). Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours. Oncogene, 20, 1509-18. https://doi.org/10.1038/sj.onc.1204175
  15. Hirsch FR, Merrick DT, Franklin WA (2002). Role of biomarkers for early detection of lung cancer and chemoprevention. Eur Respir J, 19, 1151-8. https://doi.org/10.1183/09031936.02.00294102
  16. Honorio S, Agathanggelou A, Schuermann M, et al (2003). Detection of RASSF1A aberrant promoter hypermethylation in sputum from chronic smokers and ductal carcinoma in situ from breast cancer patients. Oncogene, 22, 147-50. https://doi.org/10.1038/sj.onc.1206057
  17. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  18. Joseph Lau M, John PA Ioannidis, MD, Christopher H Schmid (1998). Summing up evidence: one answer is not always enough. The Lancet, 351, 123-7. https://doi.org/10.1016/S0140-6736(97)08468-7
  19. Lee SM, Lee WK, Kim DS, et al (2012). Quantitative promoter hypermethylation analysis of RASSF1A in lung cancer: comparison with methylation-specific PCR technique and clinical significance. Mol Med Rep, 5, 239-44.
  20. Li W, Deng J, Jiang P, et al (2012). Methylation of the RASSF1A and RARbeta genes as a candidate biomarker for lung cancer. Exp Ther Med, 3, 1067-71.
  21. Li W, Deng J, Tang JX (2014). Combined effects methylation of FHIT, RASSF1A and RARbeta genes on non-small cell lung cancer in the Chinese population. Asian Pac J Cancer Prev, 15, 5233-7. https://doi.org/10.7314/APJCP.2014.15.13.5233
  22. Lin Q, Geng J, Ma K, et al (2009). RASSF1A, APC, ESR1, ABCB1 and HOXC9, but not p16INK4A, DAPK1, PTEN and MT1G genes were frequently methylated in the stage I non-small cell lung cancer in China. J Cancer Res Clin Oncol, 135, 1675-84. https://doi.org/10.1007/s00432-009-0614-4
  23. Mantel N, Haenszel W (1959). Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst, 22, 719-48.
  24. Niklinski J, Niklinska W, Chyczewski L, et al (2005). Prognostic value of aberrant promoter methylation of DAPK and RASSF1A genes in early stage of non-small cell lung cancer (NSCLC). Lung Cancer, 49, 293-S.
  25. Safar AM, Spencer H, 3rd, Su X, et al (2005). Methylation profiling of archived non-small cell lung cancer: a promising prognostic system. Clin Cancer Res, 11, 4400-5. https://doi.org/10.1158/1078-0432.CCR-04-2378
  26. Wang J, Lee JJ, Wang L, et al (2004). Value of p16INK4a and RASSF1A promoter hypermethylation in prognosis of patients with resectable non-small cell lung cancer. Clin Cancer Res, 10, 6119-25. https://doi.org/10.1158/1078-0432.CCR-04-0652
  27. Wang Y, Yu Z, Wang T, et al (2007). Identification of epigenetic aberrant promoter methylation of RASSF1A in serum DNA and its clinicopathological significance in lung cancer. Lung Cancer, 56, 289-94. https://doi.org/10.1016/j.lungcan.2006.12.007
  28. WIL BWSaCP (D2014). World Cancer Report 2014. World Health Organization.
  29. Yanagawa N, Tamura G, Oizumi H, et al (2007). Promoter hypermethylation of RASSF1A and RUNX3 genes as an independent prognostic prediction marker in surgically resected non-small cell lung cancers. Lung Cancer, 58, 131-8. https://doi.org/10.1016/j.lungcan.2007.05.011
  30. Zhai X, Li SJ (2014). Methylation of RASSF1A and CDH13 genes in individualized chemotherapy for patients with non-small cell lung cancer. Asian Pac J Cancer Prev, 15, 4925-8. https://doi.org/10.7314/APJCP.2014.15.12.4925
  31. Zhang H, Zhang S, Zhang Z, et al (2010). Prognostic value of methylation status of RASSF1A gene as an independent factor of non-small cell lung cancer. Zhongguo Fei Ai Za Zhi, 13, 311-6 (in Chinese).

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