Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Folate Deficiency and FHIT Hypermethylation and HPV 16 Infection Promote Cervical Cancerization

  • Bai, Li-Xia (Maternal and Children Health care of Shanxi Province affiliated to Shanxi Medical University) ;
  • Wang, Jin-Tao (Department of Epidemiology, School of Public Health, Shanxi Medical University) ;
  • Ding, Ling (Department of Epidemiology, School of Public Health, Shanxi Medical University) ;
  • Jiang, Shi-Wen (Department of Biomedical Science, Mercer University School of Medicine) ;
  • Kang, Hui-Jie (Department of Epidemiology, School of Public Health, Shanxi Medical University) ;
  • Gao, Chen-Fei (Department of Epidemiology, School of Public Health, Shanxi Medical University) ;
  • Chen, Xiao (Department of Epidemiology, School of Public Health, Shanxi Medical University) ;
  • Chen, Chen (Department of Epidemiology, School of Public Health, Shanxi Medical University) ;
  • Zhou, Qin (Department of Epidemiology, School of Public Health, Shanxi Medical University)
  • Published : 2014.11.28
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Abstract

Fragile histidine triad (FHIT) is a suppressor gene related to cervical cancer through CpG island hypermethylation. Folate is a water-soluble B-vitamin and an important cofactor in one-carbon metabolism. It may play an essential role in cervical lesions through effects on DNA methylation. The purpose of this study was to observe effects of folate and FHIT methylation and HPV 16 on cervical cancer progression. In this study, DNA methylation of FHIT, serum folate level and HPV16 status were measured using methylation-specific polymerase chain reaction (MSP), radioimmunoassay (RIA) and polymerase chain reaction (PCR), respectively, in 310 women with a diagnosis of normal cervix (NC, n=109), cervical intraepithelial neoplasia (CIN, n=101) and squamous cell carcinoma of the cervix (SCC, n=101). There were significant differences in HPV16 status (${\chi}^2=36.64$, P<0.001), CpG island methylation of FHIT (${\chi}^2=71.31$, P<0.001) and serum folate level (F=4.57, P=0.011) across the cervical histologic groups. Interaction analysis showed that the ORs only with FHIT methylation (OR=11.47) or only with HPV 16 positive (OR=4.63) or with serum folate level lower than 3.19ng/ml (OR=1.68) in SCC group were all higher than the control status of HPV 16 negative and FHIT unmethylation and serum folate level more than 3.19ng/ml (OR=1). The ORs only with HPV 16 positive (OR=2.58) or with serum folate level lower than 3.19ng/ml (OR=1.28) in CIN group were all higher than the control status, but the OR only with FHIT methylation (OR=0.53) in CIN group was lower than the control status. HPV 16 positivity was associated with a 7.60-fold increased risk of SCC with folate deficiency and with a 1.84-fold increased risk of CIN. The patients with FHIT methylation and folate deficiency or with FHIT methylation and HPV 16 positive were SCC or CIN, and the patients with HPV 16 positive and FHIT methylation and folate deficiency were all SCC. In conclusion, HPV 16 infection, FHIT methylation and folate deficiency might promote cervical cancer progression. This suggests that FHIT may be an effective target for prevention and treatment of cervical cancer.

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References

  1. Abike F, Engin AB, Dunder I, et al (2011). Human papilloma virus persistence and neopterin, folate and homocysteine levels in cervical dysplasias. Arch Gynecol Obstet, 284, 209-14. https://doi.org/10.1007/s00404-010-1650-7
  2. Abouzeid HE, Kassem AM, Abdel Wahab AH, et al (2011). Promoter hypermethylation of RASSF1A, MGMT, and HIC-1 genes in benign and malignant colorectal tumors. Tumour Biol, 32, 845-52. https://doi.org/10.1007/s13277-011-0156-7
  3. Al-Temaimi RA, Jacob S, Al-Ali W, et al (2013). Reduced FHIT expression is associated with mismatch repair deficient and high CpG island methylator phenotype colorectal cancer. J Histochem Cytochem, 61, 627-38. https://doi.org/10.1369/0022155413497367
  4. Banzai C, Nishino K, Quan J, et al (2014). Promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A genes in cervical carcinoma. Int J Clin Oncol, 19, 127-32. https://doi.org/10.1007/s10147-013-0530-0
  5. Chen X, Li P, Yang Z, Mo WN (2013). Expression of fragile histidine triad (FHIT) and WW-domain oxidoreductase gene (WWOX) in nasopharyngealcarcinoma. Asian Pac J Cancer Prev, 14, 165-71. https://doi.org/10.7314/APJCP.2013.14.1.165
  6. Ding L, Ma J, Zhou Q, Wang J (2013). Effect of folate on the proliferation of human cervical cancer cell and relationship with HPV16. Wei Sheng Yan Jiu, 42, 748-53.
  7. Flatley JE, McNeir K, Balasubramani L, et al (2009). Folate Status and Aberrant DNA Methylation Are Associated With HPV Infection and Cervical Pathogenesis. Cancer Epidemiol Biomarkers Prev, 18, 2782-9. https://doi.org/10.1158/1055-9965.EPI-09-0493
  8. Han Y, Zhang Z, Zhang GJ, et al (2011). Aberrant FHIT expression is linked to bladder carcinogenesis and apoptosis. Asian Pac J Cancer Prev, 12, 2915-20.
  9. Haroun RA, Zakhary NI, Mohamed MR, et al (2014). Assessment of the prognostic value of methylation status and expression levels of FHIT, GSTP1 and p16 in non-small cell lung cancer in Egyptian patients. Asian Pac J Cancer Prev, 15, 4281-7. https://doi.org/10.7314/APJCP.2014.15.10.4281
  10. Jeong YJ, Jeong HY, Lee SM, et al (2013). Promoter methylation status of the FHIT gene and Fhit expression: association with HER2/neu status in breast cancer patients. Oncol Rep, 30, 2270-8.
  11. Jin-Tao W, Ling D, Shi-Wen J, et al (2014). Folate Deficiency and Aberrant Expression of DNA Methyltransferase 1 were Associated with Cervical Cancerization. Curr Pharm Des, 20, 1639-46. https://doi.org/10.2174/13816128113199990543
  12. Li W, Deng J, Tang JX (2014). Combined effects methylation of FHIT, RASSF1A and RAR$\beta$ 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
  13. Neyaz MK, Kumar RS, Hussain S, et al (2008). Effect of aberrant promoter methylation of FHIT and RASSF1A genes on susceptibility to cervical cancer in a North Indian population. Biomarkers, 13, 597-606. https://doi.org/10.1080/13547500802078859
  14. Pathak S, Bhatla N, Singh N (2012). Cervical cancer pathogenesis is associated with one-carbon metabolism. Mol Cell Biochem, 369, 1-7. https://doi.org/10.1007/s11010-012-1362-3
  15. Piyathilake CJ, Henao OL, Macaluso M, et al (2004). Folate is associated with the natural history of high-risk human papillomaviruses. Cancer Res, 64, 8788-93. https://doi.org/10.1158/0008-5472.CAN-04-2402
  16. Piyathilake CJ, Macaluso M, Brill I, et al (2007). Lower red blood cell folate enhances the HPV-16-associated risk of cervical intraepithelial neoplasia. Nutrition, 23, 203-10. https://doi.org/10.1016/j.nut.2006.12.002
  17. Piyathilake CJ, Badiga S, Paul P, et al (2010). Indian women with higher serum concentrations of folate and vitamin B12 are significantly less likely to be infected with carcinogenic or high-risk (HR) types of human papillomaviruses (HPVs). Int J Womens Health, 2, 7-12.
  18. Piyathilake CJ, Macaluso M, Celedonio JE, et al (2010). Mandatory fortification with folic acid in the United States appears to have adverse effects on histone methylation in women with pre-cancer but not in women free of pre-cancer. Int J Womens Health, 9, 131-7.
  19. Piyathilake CJ, Macaluso M, Alvarez RD, et al (2011). A higher degree of LINE-1 methylation in peripheral blood mononuclear cells, a one-carbon nutrient related epigenetic alteration, is associated with a lower risk of developing cervical intraepithelial neoplasia. Nutrition, 27, 513-9. https://doi.org/10.1016/j.nut.2010.08.018
  20. Ragasudha PN, Thulaseedharan JV, Wesley R, et al (2012). A case-control nutrigenomic study on the synergistic activity of folate and vitamin B12 in cervical cancer progression. Nutr Cancer, 64, 550-8. https://doi.org/10.1080/01635581.2012.675618
  21. Shi HR, Wu QH, Suo ZH, Nesland JM (2005). Correlation between methylation of 5'-CpG islands and inactivation of FHIT gene in cervical cancer. Ai Zheng, 24, 7-11.
  22. Tan S, Sun C, Wei X, et al (2013). Quantitative assessment of lung cancer associated with genes methylation in the peripheral blood. Exp Lung Res, 39, 182-90. https://doi.org/10.3109/01902148.2013.790096
  23. Tomaszewski JJ, Cummings JL, Parwani AV, et al (2011). Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate. Prostate, 71, 1287-93.
  24. Tong SY, Kim MK, Lee JK, et al (2011). Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12. Cancer Causes Control, 22, 63-72. https://doi.org/10.1007/s10552-010-9675-6
  25. Wang JT, Huo XX, Ding L, et al (2011). Effect of folic acid and DNA methyltransferase 1 on cervical cancer and its precancerous lesion. Zhonghua Liu Xing Bing Xue Za Zhi, 32, 617-21.
  26. Wilke CM, Hall BK, Hoge A, et al (1996). FRA3B extends over a broad region and contains a spontaneous HPV16 integration site: direct evidence for the coincidence of viral integration sites and fragile sites. Hum Mol Genet, 5, 187-95. https://doi.org/10.1093/hmg/5.2.187
  27. Zhang Y, Chen FQ, Sun YH, et al (2011). Effects of DNMT1 silencing on malignant phenotype and methylated gene expression in cervical cancer cells. J Exp Clin Cancer Res, 17, 98.

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