Introduction to the role of fragile histidine triad (fhit) gene in cancer: A review of literature with special emphasis on cervical carcinoma

International Journal of Cancer Research

Volumn 7, Issue 2, 2011, Pages 99-113

  Sultana, S A ^a   Kiranmayee, S ^b   Bammidi, V K ^b   Shaik, Abjal Pasha ^c   Jamil, K ^c  

^a Golden Homes   (India)

^b Stapenhill Medical Centre   (United Kingdom)

^c JNT University Anantapur   (India)

Author keywords

Cancer; Cervical cancer; fhit; Fragile histidine triad gene

Indexed keywords

FRAGILE HISTIDINE TRIAD PROTEIN;

BLADDER CANCER; BREAST CANCER; CANCER GENETICS; COLORECTAL CANCER; ESOPHAGUS CANCER; FRAGILE HISTIDINE TRIAD GENE; GENE EXPRESSION; GENE FUNCTION; GENE MUTATION; HEAD AND NECK CANCER; HUMAN; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; LUNG CANCER; NONHUMAN; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; REVIEW; SEBACEOUS CARCINOMA; STOMACH CANCER; THYROID TUMOR; TUMOR SUPPRESSOR GENE; UTERINE CERVIX CANCER;

EID: 79957954348     PISSN: 18119727     EISSN: 18119735     Source Type: Journal    
DOI: 10.3923/ijcr.2011.99.113     Document Type: Review

References (94)

1. Abend, A., P.N. Garrison, L.D. Barnes and P.A. Frey, 1999. Stereochemical retention of the configuration in the action of fhit on phosphorus-chiral substrates. Biochemistry, 38: 3668-3676.
2. Alani, R.M. and K. Munger, 1998. Human papillomaviruses and associated malignancies. J. Clin. Oncol., 16: 330-337.
3. Bahnassy, A.A., A.R. Zekri, M.S. Madbouly, M. El-Naggar, Z.F. El-Khelany and M.M. El-Merzebany, 2006. The correlation between FHIT, P53 and MMR genes in human papillomavirus-associated cervical carcinoma. J. Egypt. Nat. Cancer Inst., 18: 191-202.
4. Barnes, L.D., P.N. Garrison, Z. Siprashvili, A. Guranowski and A.K. Robinson et al., 1996. Fhit, a putative tumor suppressor in humans is a dinucleoside 5',5'''-P1, P3-triphosphate hydrolase. Biochemistry, 35: 11529-11535.
5. Baykal, C., A. Ayhan, A. Al, K. Yuce and A. Ayhan, 2003. No relationship is indicated between FHIT expression and clinicopathologic prognostic parameters in early stage cervical carcinoma. Int. J. Gynecol. Cancer, 13: 192-196.
6. Becker, N.A., E.C. Thorland, S.R. Demson, L.A. Phillips and D.I. Smith, 2002. Evidence that instability within the FRA3B region extends four megabases. Oncogene, 21: 8713-8722.
7. Bianchi, F., E. Tagliabue, S. Menard and M. Campiglio, 2007. Fhit expression protects against HER2-driven breast tumor development: unraveling the molecular interconnections. Cell Cycle, 6: 643-646.
8. Birrer, M.J., D. Hendricks, J. Farley, M.J. Sundborg, T. Bonome, M.J. Walts and J. Geradts, 1999. Abnormal fhit expression in malignant and premalignant lesions of the cervix. Cancer Res., 59: 5270-5274.
9. Bosch, F.X., M.M. Manos, N. Muaoz, M. Sherman and A.M. Jansen et al., 1995. Prevalence of human papillomavirus in cervical cancer: A worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J. Nat. Cancer Inst., 87: 796-802.
10. Capuzzi, D., E. Santoro, W.W. Hauck, A.J. Kovatich and F.E. Rosato et al., 2000. FHIT expression in gastric adenocarcinoma: correlation with disease stage and survival. Cancer, 88: 24-34.
11. Choi, C.H., K.M. Lee, J.J. Choi, T.J. Kim and W.Y. Kim et al., 2007. Hypermethylation and loss of heterozygosity of tumor suppressor genes on chromosome 3p in cervical cancer. Cancer Lett., 255: 26-33.
12. Chu, T.Y., C.Y. Shen, Y.S. Chiou, J.J. Lu, C.L. Perng, M.S. Yu and H.S. Liu, 1998. HPV-associated cervical cancers show frequent allelic loss at 3p14 but no apparent aberration of FHIT mRNA. Int. J. Cancer, 75: 199-204.
13. Connolly, D.C., D.L. Greenspan, R. Wu, X. Ren and R.L. Dunn et al., 2000. Loss of fhit expression in invasive cervical carcinomas and intraepithelial lesions associated with invasive disease. Clin. Cancer Res, 6: 3505-3510.
14. Corbin, S., M.E. Neilly, R. Espmosa, E.M. Davis, T.W. McKeithan and M.M. Le Beau, 2002. Identification of unstable sequences within the common fragile site at 3p14.2: Implications for the mechanism of deletions within fragile histidine triad gene/common fragile site at 3p14.2 in tumors. Cancer Res, 62: 3477-3484.
15. Croce, C.M., G. Sozzi and K. Huebner, 1999. Role of FHIT in human cancer. J. Clin. Oncol, 17: 1618-1624.
16. Druck, T., P. Hadaczek, T.B. Fu, M. Ohta and Z. Siprashvili et al., 1997. Structure and expression of the human FHIT gene in normal and tumor cells. Cancer Res, 57: 504-512.
17. Dumon, K.R., H. Ishii, L.Y. Fong, N. Zanesi and V. Fidanza et al., 2001. FHIT gene therapy prevents tumor development in fhit-deficient mice. Proc. Nat. Acad. Sci. USA, 98: 3346-3351.
18. Elnatan, J., D. Murphy, H.S. Goh and D.R. Smith, 1999. HIT family genes: FHIT but not PKCI-1/HINT produces altered transcripts in colorectal cancer. Br. J. Cancer, 81: 874-880.
19. Evander, M., K. Edlund, A. Gustafsson, M. Jonsson, R. Karlsson, E. Rylander and G. Wadell, 1995. Human papillomavirus infection is transient in young women: a population-based cohort study. J. Infect. Dis, 171: 1026-1030.
20. Feng, X., L. Li, Y. Gao, J. Zhang and J. Ying et al., 2007. fhit protein expression in lung cancer studied by high-throughput tissue microarray. Bull. Cancer, 94: E8-11.
21. Fong, K.M., E.J. Biesterveld, A. Virmani, I. Wistuba and Y. Sekido et al., 1997. FHIT and FRA3B 3p14.2 allele loss are common in lung cancer and preneoplastic bronchial lesions and are associated with cancer-related FHIT cDNA splicing aberrations. Cancer Res., 57: 2256-2267.
22. Fong, L.Y., Y. Fidanza, N. Zanesi, L.F. Lock and L.D. Siracusa et al., 2000. Muir-torre-like syndrome in fhit-deficient mice. Proc. Nat. Acad. Sci. USA., 97: 4742-4747.
23. Gayrard, N., Y. Cacheux, F. Iborra, G. Mourad and A. Argiles, 2008. Cytogenetic studies of 24 renal epithelial tumors with von Hippel-Lindau and fragile histidine triad protein expression correlation. Arch. Pathol. Lab. Med., 132: 965-973.
24. Gemmill, R.M., J.D. West, F. Boldog, N. Tanaka and L.J. Robinson et al., 1998. The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8. Proc. Nat. Acad. Sci. USA, 95: 9572-9577.
25. Geradts, J., K.M. Fong, P.V. Zimmerman and J.D. Minna, 2000. Loss of fhit expression in non-small-cell lung cancer: Correlation with molecular genetic abnormalities and clinicopathological features. Br. J. Cancer, 82: 1191-1197.
26. Geurts, J.M., E.F. Schoenmakers, E. Roijer, G. Stenman and W.J. van de Ven, 1997. Expression of reciprocal hybrid transcripts of HMGIC and FHIT in a pleomorphic adenoma of the parotid gland. Cancer Res, 57: 13-17.
27. Greenspan, D.L., D.C. Connolly, R. Wu, R.Y. Lei and J.T. Vogelstein et al., 1997. Loss of FHIT expression in cervical carcinoma cell lines and primary tumors. Cancer Res, 57: 4692-4698.
28. Guler, G., A. Uner, N. Guler, S.Y. Han and D. Iliopoulos et al., 2004. The fragile genes FHIT and WWOX are inactivated coordinately in invasive breast carcinoma. Cancer, 100: 1605-1614.
29. Guler, G., K. Huebner, C. Himmetoglu, R.E. Jimenez and S. Costinean et al., 2009. Fragile histidine triad protein, WW domain-containing oxidoreductase protein Wwox and activator protein 2gamma expression levels correlate with basal phenotype in breast cancer. Cancer, 115: 899-908.
30. Holbach, L.M., A. von Moller, C. Decker, A.G. Junemann, C. Rummelt-Hofmann and W.G. Ballhausen, 2002. Loss of fragile histidine triad (FHIT) expression and microsatellite instability in periocular sebaceous gland carcinoma in patients with Muir-Torre syndrome. Am. J. Ophthalmol, 134: 147-148.
31. Holschneider, C.H., R.L. Baldwin, K. Tumber, C. Aoyama and B.Y. Karlan, 2005. The fragile histidine triad gene: A molecular link between cigarette smoking and cervical cancer. Clin. Cancer Res, 11: 5756-5763.
32. Hsieh, C.L. and P.A. Jones, 2003. Meddling with methylation. Nation Cell. Biol, 5: 502-504.
33. Huang, K., A. Arabshahi, Y. Wei and P.A. Frey, 2004. The mechanism of action of the fragile histidine triad, Fhit: Isolation of a covalent adenylyl enzyme and chemical rescue of H96G-Fhit. Biochemistry, 43: 7637-7642.
34. Huebner, K. and C.M. Croce, 2001. FRA3B and other common fragile sites: The weakest links. Nat. Rev. Cancer, 1: 214-221.
35. Huebner, K. and C.M. Croce, 2003. Cancer and the FRA3B/FHIT fragile locus: It's a HIT. Br. J. Cancer, 88: 1501-1506.
36. Inoue, H., H. Ishii, H. Alder, E. Snyder, T. Druck, K. Huebner and C.M. Croce, 1997. Sequence of the FRA3B common fragile region: Implications for the mechanism of FHIT deletion. Proc. Nat. Acad. Sci. USA, 94: 14584-14589.
37. Ishii, H., K. Mimori, H. Inoue, T. Inageta and K. Ishikawa et al., 2006. Fhit modulates the DNA damage checkpoint response. Cancer Res, 66: 11287-11292.
38. Ishii, H., Y. Wang and K. Huebner, 2007. A fhit-ing role in the DNA damage checkpoint response. Cell Cycle, 6: 1044-1048.
39. Kannan, K., A.K. Munirajan, Y. Bhuvarahamurthy, B.K. Mohanprasad, P. Shankar, N. Tsuchida and G. Shanmugam, 2000. FHIT gene mutations and single nucleotide polymorphism in Indian oral and cervical squamous cell carcinomas. Oral. Oncol, 36: 189-193.
40. Larson, G.P., Y. Ding, L.S. Cheng, C. Lundberg and Y. Gagalang et al., 2005. Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT. Cancer Res, 65: 805-814.
41. Latil, A., I. Bieche, G. Fournier, O. Cussenot, S. Pesche and R. Lidereau, 1998. Molecular analysis of the FHIT gene in human prostate cancer. Oncogene, 16: 1863-1868.
42. Lee, S.H., C.J. Kim, H.K. Park, J.W. Koh, M.H. Cho, M.J. Baek and M.S. Lee, 2001a. Characterization of aberrant FHIT transcripts in gastric adenocarcinomas. Exp. Mol. Med, 33: 124-130.
43. Lee, S.H., W.H. Kim, H.K. Kim, K.M. Woo and H.S. Nam et al., 2001b. Altered expression of the fragile histidine triad gene in primary gastric adenocarcinomas. Biochem. Biophys. Res. Commun, 284: 850-855.
44. Lopez-Beltran, A. and E. Munoz, 1995. Transitional cell carcinoma of the bladder: Low incidence of human papillomavirus DNA detected by the polymerase chain reaction and in situ hybridization. Histopathology, 26: 565-569.
45. Mao, L., Y.H. Fan, R. Lotan and W.K. Hong, 1996. Frequent abnormalities of FHIT, a candidate tumor suppressor gene in head and neck cancer cell lines. Cancer Res, 56: 5128-5131.
46. Maruyama, R, S. Toyooka, K.O. Toyooka, K. Harada and A.K. Yirmani et al., 2001. Aberrant promoter methylation profile of bladder cancer and its relationship to clinicopathological features. Cancer Res, 61: 8659-8663.
47. Mclver, B., S.K. Grebe, L. Wang, I.D. Hay and A. Yokomizo et al., 2000. FHIT and TSG101 in thyroid tumours: Aberrant transcripts reflect rare abnormal RNA processing events of uncertain pathogenetic or clinical significance. Clin. Endocrinol, 52: 749-757.
48. Mimori, K., H. Inoue, T. Shiraishi, A. Matsuyama, K. Mafune, Y. Tanaka and M. Mori, 2003. Microsatellite instability is often observed in esophageal carcinoma patients with allelic loss in the FHIT/FRA3B locus. Oncology, 64: 275-279.
49. Mori, M., K. Mimori, T. Masuda, K. Yoshinaga, K. Yamashita, A. Matsuyama and H. Inoue, 2001. Absence of Msh2 protein expression is associated with alteration in the FHIT locus and fhit protein expression in colorectal carcinoma. Cancer Res, 61: 7379-7382.
50. Morikawa, H., Y. Nakagawa, K. Hashimoto, M. Niki and Y. Egashira et al., 2000. Frequent altered expression of fragile histidine triad protein in human colorectal adenomas. Biochem. Biophys. Res. Commun, 278: 205-210.
51. Muller, C.Y., J.D. O'Boyle, K.M. Fong, Wistuba and E. Biesterveld et al., 1998. Abnormalities of fragile histidine triad genomic and complementary DNAs in cervical cancer: Association with human papillomavirus type. J. Nat. Cancer Inst, 90: 433-439.
52. Munoz, N., I. Kato, F.X. Bosch, S. de Sanjose and V.A. Sundquist et al., 1995. Cervical cancer and herpes simplex virus type 2: case-control studies in Spain and Colombia, with special reference to immunoglobulin-G sub-classes. Int. J. Cancer, 60: 438-442.
53. Nakagawa, S., H. Yoshikawa, M. Kimura, K. Kawana and K. Matsumoto et al., 1999. A possible involvement of aberrant expression of the FHIT gene in the carcinogenesis of squamous cell carcinoma of the uterine cervix. Br. J. Cancer, 79: 589-594.
54. Nan, K.J., Z.P. Ruan, Z. Jing, H.X. Qin, H.Y. Wang, H. Guo and R. Xu, 2005. Expression of fragile histidine triad in primary hepatocellular carcinoma and its relation with cell proliferation and apoptosis. World J. Gastroenterol, 11: 228-231.
55. Negrini, M., C. Monaco, I. Yorechovsky, M. Ohta and T. Druck et al., 1996. The FHIT gene at 3p14.2 is abnormal in breast carcinomas. Cancer Res, 56: 3173-3179.
56. Neyaz, M.K., R.S. Kumar, S. Hussain, S.H. Naqvi and I. Kohaar 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.
57. Neyaz, M.K., S. Hussain, M.I. Hassan, B.C. Das, S.A. Husain and M. Bharadwaj, 2010. Novel missense mutation in FHIT gene: Interpreting the effect in HPV-mediated cervical cancer in Indian women. Mol. Cell. Biochem, 335: 53-58.
58. Noronha, V., W. Mello, L. Villa, A. Brito and R. Macedo et al., 1999. Human papillomavirus associated with uterine cervix lesions. Rev. Soc. Bras. Med. Trop, 32: 235-340.
59. Ohta, M., H. Inoue, M.G. Cotticelli, K. Kastury and R. Baffa et al., 1996. The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint is abnormal in digestive tract cancers. Cell, 84: 587-597.
60. Pace, H.C., P.N. Garrison, A.K. Robinson, L.D. Barnes and A. Draganescu et al., 1998. Genetic, biochemical and crystallographic characterization of fhit-substrate complexes as the active signaling form of Fhit. Proc. Nat. Acad. Sci. USA, 95: 5484-5489.
61. Paradiso, A., G. Ranieri, B. Stea, A. Zito and I. Zehbe et al., 2004. Altered pl6INK4a and fhit expression in carcinogenesis and progression of human oral cancer. Int. J. Oncol, 24: 249-255.
62. Parkin, D.M., P. Pisani and J. Ferlay, 1999. Estimates of the worldwide incidence of 25 major cancers in 1990. Int. J. Cancer, 80: 827-841.
63. Pekarsky, Y., P.N. Garrison, A. Palamarchuk, N. Zanesi and R.I. Aqeilan et al., 2004. Fhit is a physiological target of the protein kinase Src. Proc. Nat. Acad. Sci. USA, 101: 3775-3779.
64. Pekarsky, Y., T. Druck, M.G. Cotticelli, M. Ohta and J. Shou et al., 1998. The murine fhit locus: Isolation, characterization and expression in normal and tumor cells. Cancer Res, 58: 3401-3408.
65. Pichiorri, F., H. Ishii, H. Okumura, F. Trapasso, Y. Wang and K. Huebner, 2008. Molecular parameters of genome instability: Roles of fragile genes at common fragile sites. J. Cell. Biochem, 104: 1525-1533.
66. Poland, K.S., M. Azim, M. Folsom, R. Goldfarb and R. Naeem et al., 2007. A constitutional balanced t(3;8)(p14;q24.1) translocation results in disruption of the TRC8 gene and predisposition to clear cell renal cell carcinoma. Genes Chromosomes Cancer, 46: 805-812.
67. Rassool, F.V., M.M. le Beau, M.L. Shen, M.E. Neilly and R. Espmosa et al., 1996. Direct cloning of DNA sequences from the common fragile site region at chromosome band 3p14.2. Genomics, 35: 109-117.
68. Santos, S.C., L.R. Cavalli, I.J. Cavalli, R.S. Lima, B.R. Haddad and E.M. Ribeiro, 2004. Loss of heterozygosity of the BRCA1 and FHIT genes in patients with sporadic breast cancer from Southern Brazil. J. Clin. Pathol, 57: 374-377.
69. Sard, L., P. Accornero, S. Tornielli, D. Delia and G. Bunone et al., 1999. The tumor-suppressor gene FHIT is involved in the regulation of apoptosis and in cell cycle control. Proc. Nat. Acad. Sci. USA, 96: 8489-8492.
70. Schiffman, M.H., H.M. Bauer, R.N. Hoover, A.G. Glass and D.M. Cadell et al., 1993. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J. Nat. Cancer Inst, 85: 958-964.
71. Segawa, T., T. Sasagawa, H. Yamazaki, J. Sakaike, H. Ishikawa and M. Inoue, 1999. Fragile histidine triad transcription abnormalities and human papillomavirus E6-E7 mRNA expression in the development of cervical carcinoma. Cancer, 85: 2001-2010.
72. Shi, Y., M. Zou, N.R. Farid and M.C. Paterson, 2000. Association of FHIT (fragile histidine triad), a candidate tumour suppressor gene with the ubiquitin-conjugating enzyme hUBC9. Biochem. J, 352: 443-448.
73. Shiraishi, T., T. Druck, K. Mimori, J. Flomenberg and L. Berk et al., 2001. Sequence conservation at human and mouse orthologous common fragile regions, FRA3B/FHIT and Fral4A2/Fhit. Proc. Nat. Acad. Sci. USA, 98: 5722-5727.
74. Siprashvili, Z., G. Sozzi, L.D. Barnes, P. McCue and A.K. Robinson et al., 1997. Replacement of fhit in cancer cells suppresses tumorigenicity. Proc. Natl. Acad. Sci, 94: 13771-13776.
75. Sozzi, G., M.L. Veronese, M. Negrmi, R. Baffa and M.G. Cotticelli et al., 1996. The FHIT gene 3p14.2 is abnormal in lung cancer. Cell, 85: 17-26.
76. Sozzi, G., L. Sard, L. de Gregorio, A. Marchetti and K. Musso et al., 1997a. Association between cigarette smoking and FHIT gene alterations in lung cancer. Cancer Res, 57: 2121-2123.
77. Sozzi, G., S. Tornielli, E. Tagliabue, L. Sard and F. Pezzella et al., 1997b. Absence of fhit protein in primary lung tumors and cell lines with FHIT gene abnormalities. Cancer Res, 57: 5207-5212.
78. Sozzi, G., U. Pastorino, L. Moiraghi, E. Tagliabue and F. Pezzella et al., 1998. Loss of FHIT function in lung cancer and preinvasive bronchial lesions. Cancer Res, 58: 5032-5037.
79. Stein, C.K., T.W. Glover, J.L. Palmer and B.S. Glisson, 2002. Direct correlation between FRA3B expression and cigarette smoking. Genes Chromosomes Cancer, 34: 333-340.
80. Strefford, J.C., I. Stasevich, T.M. Lane, Y.J. Lu, T. Oliver and B.D. Young, 2005. A combination of molecular cytogenetic analyses reveals complex genetic alterations in conventional renal cell carcinoma. Cancer Genet. Cytogenet, 159: 1-9.
81. Su, T.H., J.C. Wang, H.H. Tseng, C.P. Chang, T.A. Chang, H.J. Wei and J.G. Chang, 1998. Analysis of FHIT transcripts in cervical and endometrial cancers. Int. J. Cancer, 76: 216-222.
82. Sukosd, F., N. Kuroda, T. Beothe, A.P. Kaur and G. Kovacs, 2003. Deletion of chromosome 3p14.2-p25 involving the VHL and FHIT genes in conventional renal cell carcinoma. Cancer Res, 63: 455-457.
83. Velickovic, M., B. Delahunt, S. Storkel and S.K. Grebem, 2001. VHL and FHIT locus loss of heterozygosity is common in all renal cancer morphotypes but differs in pattern and prognostic significance. Cancer Res, 61: 4815-4819.
84. Virgilio, L., M. Shuster, S. Gollin, M.L. Veronese and M. Ohta, 1996. FHIT gene alterations in head and neck squamous cell carcinomas. Proc. Natl. Acad. Sci, 93: 9770-9775.
85. Wang, T.T., E.E. Frezza, R. Ma, S.Y. Hu and C.Z. Liu et al., 2008. Loss expression of active fragile sites genes associated with the severity of breast epithelial abnormalities. Chin. Med. J., 121: 1969-1974.
86. Wei, Y., J. Ko, L.F. Murga and M.J. Ondrechen, 2007. Selective prediction of interaction sites in protein structures with thematics. BMC Bioinformatics, 8: 119-119.
87. Weiske, J., K.F. Albring and O. Huber, 2007. The tumor suppressor fhit acts as a repressor of beta-catenin transcriptional activity. Proc. Nat. Acad. Sci. USA, 104: 20344-20349.
88. Yang, Q., M. Nakamura, Y. Nakamura, G. Yoshimura and T. Suzuma et al., 2002. Two-hit inactivation of FHIT by loss of heterozygosity and hypermethylation in breast cancer. Clin. Cancer Res, 8: 2890-2893.
89. Yoshino, K., T. Enomoto, T. Nakamura, H. Sun and K. Ozaki et al., 2000. FHIT alterations in cancerous and non-cancerous cervical epithelium. Int. J. Cancer, 85: 6-13.
90. Yoshino, K., T. Enomoto, T. Nakamura, R. Nakashima, H. Wada, J. Saitoh, K. Noda and Y. Murata, 1998. Aberrant FHIT transcripts in squamous cell carcinoma of the uterine cervix. Int. J. Cancer, 76: 176-181.
91. Zanesi, N., Y. Fidanza, L.Y. Fong, R. Mancini and T. Druck et al., 2001. The tumor spectrum in FHIT-deficient mice. Proc. Nat. Acad. Sci. USA, 98: 10250-10255.
92. Zekri, A.R., A.A. Bahnassy, M. Hafez, A.M. El-Shehaby, G.M. Sherif, H.M. Khaled and N. Zakhary, 2005. Alterations of the fragile histidine triad gene in hepatitis C virus-associated hepatocellular carcinoma. J. Gastroenterol. Hepatol, 20: 87-94.
93. Zheng, H., H. Takahashi, Y. Murai, Z. Cui, K. Nomoto, K. Tsuneyama and Y. Takano, 2007. Low expression of FHIT and PTEN correlates with malignancy of gastric carcinomas: Tissue-array findings. Applied Immunohistochem. Mol. Morphol, 15: 432-440.
94. Zur Hausen, H., 1990. The role of papillomaviruses in anogenital cancer. Scand. J. Infect. Dis. Suppl, 69: 107-111.