- Volume 14 Issue 1
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Significance of HPV Infection and Genic Mutation of APC and K-ras in Patients with Rectal Cancer
- Sun, Zhen-Qiang (Deparment of Abdomen Surgery, Affiliated Tumor Hospital, Xinjiang Medical University) ;
- Wang, Hai-Jiang (Deparment of Abdomen Surgery, Affiliated Tumor Hospital, Xinjiang Medical University) ;
- Zhao, Ze-Liang (Deparment of Abdomen Surgery, Affiliated Tumor Hospital, Xinjiang Medical University) ;
- Wang, Qi-San (Deparment of Abdomen Surgery, Affiliated Tumor Hospital, Xinjiang Medical University) ;
- Fan, Chuan-Wen (Tumor Research Institute, Huaxi Clinical Medicine College, Sichuan University) ;
- Kureshi, Kureshi (Key Laboratory of Endemic and Molecular Biology) ;
- Fang, Fa (Deparment of Abdomen Surgery, Affiliated Tumor Hospital, Xinjiang Medical University)
- Published : 2013.01.31
Background: Significance of HPV infection and genic mutation of APC and K-ras in rectal cancer has been investigated but not clarified. The objective of our study was to investigate these parameters in patients with rectal cancer to analyze correlations with biological behaviour, to determine relationships among the three, and also to demonstrate survival prognosis effects. Methods: From December 2007 to September 2008, 75 rectal cancer cases confirmed by histopathology in the Tumor Hospital of Xinjiang Medical University were enrolled. The control group consisted of normal rectal mucous membrane taken simultaneously, a least 10 cm distant from the carcinoma fringe. HPV DNA, the MCR of APC and exon-1 of K-ras were detected by PCR and PCR-SSCP. All results were analyzed in relation to clinical pathological material, using chi-square and correlation analysis via SPSS.13 and Fisher's Exact Probability via STATA. 9.0. All 75 patients were followed up for survival analysis using Kaplan-Meier and Log-rank tests. Results: 55 out of 75 cases demonstrated gene HPV L1 while it was notdetected in normal rectal mucosa tissue. HPV infection was correlated with age and lymphatic metastasis (P<0.05) but not other characteristics, such as ethnicity, tumor size, histological type, tumor type, Duke's stage and infiltration depth. Some 43 cases exhibited APC genic mutation (57.3%) and 34 K-ras genic mutation (45.3%). APC genic mutation was correlated with gender(P<0.05), but not age, histological type, infiltration depth, lymphatic metastasis and Duke's stage. In 55 cases of rectal cancer with HPV infection, there were 31 cases with genic mutation of APC (56.4%) and 24 with genic mutation of K-ras (43.6%). For the 20 cases of rectal cancer with non-HPV infection, the figures were 12 cases (60%) and 10 (50.0%), respectively, with no significant relation. Survival analysis showed no statistical significance for K-ras genic mutation, APC genic mutation or HPV infection (P>0.05). However, the survival time of the patients with HPV infection was a little shorter than in cases without HPV infection. Conclusions: Our results suggest that HPV infection might be an important factor to bring about malignant phenotype of rectal cancer and influence prognosis. Genic mutation of APC and K-ras might be common early molecular events of rectal cancer, but without prognostic effects on medium-term or early stage patients with rectal cancer.
- Tang WZ, Gao F, Li W, et al (2006). Detection of genic mutation of APC, K-ras and P53 of colorectal cancer. Tumor, 26, 282-4.
- Yavuzer D, Karadayi N, Aalepci T, et al (2010). Investigation of human papillomavirus DNA in colorectal carcinomas and adenomas. Med Oncol, 28, 127-32.
- Yuan P, Sun MH, Zhang JS, et al(2001). APC and K-ras gene mutation in aberrant crypt foci of human colon. World J Gastroenterol,7,352-6.
- Zhan QM (2005). Molecular Tumorology.Beijing,People's Medical Publishing House, 80-150.
- Zhou ZG, Chen Y (2004). Application of molecular biology in rectal cancer. Chin J Gastrointestinal Surg, 7, 172-4.
- Pochylski T, Kwasniewska A (2003). Absence of point mutation in codons 12 and 13 of K-ras oncogene in HPV-associated high grade dysplasia and squamous cell cervical carcinoma. Eur J Obstet Gynecol Reprod Biol, 111, 68-73. https://doi.org/10.1016/S0301-2115(03)00205-7
- Ogino S, Meyerhardt JA, Irahara N, et a1 (2009). K-ras mutation in stage III colon cancer and clinical outcome following intergroup trail CALGB89803. Clin Cancer Res, 15, 7322-9. https://doi.org/10.1158/1078-0432.CCR-09-1570
- Onozato W, Yamashita K, Yamashito K, et al (2011). Genetic alterations of K-ras may reflect prognosis in stage III colon cancer patients below 60 years of age. J Surg Oncol, 103, 25-33. https://doi.org/10.1002/jso.21710
- Orita M, Wahana H, Kanazawa AH, et al (1989). Detection of poly-morphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA, 86, 2766-70. https://doi.org/10.1073/pnas.86.8.2766
- Poovorawan K, Suksawatamnuay S, Sahakitrungruang C, et al (2012). Colon cancer prevention by detection of APC gene mutation in a family with attenuated familial adenomatous polyposis. Asian Pac J Cancer Prev, 13, 5101-4 https://doi.org/10.7314/APJCP.2012.13.10.5101
- Serbomaa K, Kiuru A, Mkosma V, et al (2000). p53 and K-ras gene mutations in carcinoma of the rectum among Finnish women. Mol Pathol, 53, 24-30. https://doi.org/10.1136/mp.53.1.24
- Shukla S, Bharti AC, Mahata S, et al (2009). Infection of human papillomaviruses in cancers of different human organ sites. Indian J Med Res, 130, 222-33.
- Von Knebel Doeberitz M, Reuschenbach M (2010). Human papillomaviruses in the pathogenesis of intraepithelial neoplasia (AIN) and carcinoma of the anus. Hautarzt, 61, 13-20. https://doi.org/10.1007/s00105-009-1809-y
- Weijenberg MP, Lüchtenborg M, de Goeij AF, et al (2007). Dietary fat and risk of colon and rectal cancer with aberrant MLH1 expression, APC or KRAS genes. Cancer Causes Control, 8, 865-79.
- Westra J, Schaapveld M, Hollema H, et al (2005). Determination of TP53 mutation is more relevant than microsatellite instability status for the prediction of disease-free survival in adjuvant-treated stage Duke's C colon cancer patients. J Clin Oncol, 23, 5635-43. https://doi.org/10.1200/JCO.2005.04.096
- Jira Chansaenroj, Apiradee Theamboonlers, Pairoj Junyangdikul, et al (2012). Whole Genome analysis of human Papillomavirus Type 16 multiple infection in cervical cancer patients. Asian Pacific J Cancer Prev, 13, 599-606. https://doi.org/10.7314/APJCP.2012.13.2.599
- Kamory E, Olasz J, Csuka O (2008). Somatic APC inactivation mechanisms in sporadic colorectal cancer cases in Hungary. Pathol Oncol Res, 14, 51-6. https://doi.org/10.1007/s12253-008-9019-y
- Karapetis CS, Khambata-Ford S, Jonker DJ, et a1 (2008). K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med, 359, 1757-65. https://doi.org/10.1056/NEJMoa0804385
- Kirgan D, Manalo P, Hall M, et al (1990). Association of human papillomavirus and colonneop lasms. Arch Surg, 125: 862-5. https://doi.org/10.1001/archsurg.1990.01410190060009
- Kirgan D, Manalo P, Mcgrego B (1990). Immunohistochemical demonstration of human papilloma virus antigen in human colon neoplasms. J Surg Res, 48, 397-402. https://doi.org/10.1016/0022-4804(90)90002-J
- Jiang KW, Wang B, Du RL, et al(2005). The relation of HPV with rectal caner happening and clinical pathological feature. Chin J Gen Surg, 20, 375-7.
- Lea IA, Jackson MA, Dunnick JK(2009). Genetic pathways to colorectal cancer. Mutat Res, 670, 96-8. https://doi.org/10.1016/j.mrfmmm.2009.06.011
- Mazurek S, Zwrschke W, Jansen-durr P, et al(2001). Metabolic cooperation between different oncogenes during cell transformation: interaction between activated ras and HPV-16 E7. Oncogene, 20, 6891-8. https://doi.org/10.1038/sj.onc.1204792
- Mlynarczyk B, Malejczyk M, Muszynski J, et al(2009). The occurrence of human papillomavirus--HPV in the biopsies from colon polyps and cancer. Med Dosw Mikrobiol, 61, 191-6.
- Palefsky JM (2010). Human papillomavirus-related disease in men: not just a women's issue. J Adolesc Health, 46, S12-9.
- Pan ZZ, Wan DS, Chen G, et al (2004). Co-mutation of p53, K-ras genes and accumulation of p53 protein and its correlation to clinicopathological features in rectal cancer. World J Gastroenterol, 15, 3688-90.
- Beliaeva AV, Ianus GA, Suspithyn EN, et al (2012). Age-related and clinical-pathogenetic features of colorectal cancer associated with status of K-ras gene. Adv Gerontol, 25, 72-8.
- Bleeker WA, Hayes VM, Karreabeld A, et a1 (2001). Prognostic significance of K-ras and TP53 mutations in the role of adjuvant chemotherapy on survival in patients with Duke's C colon cancer. Dis Colon Rectum, 44, 358-63. https://doi.org/10.1007/BF02234733
- Brennan MM, Lambkin HA, Sheehan CD, et al (2001). Detection of high-risk subtypes of human papillomavirus in cervical swabs: routine use of the Digene Hybrid Capture assay and polymerase chain reaction analysis. Br J Biomed Sci, 58, 24-9.
- Chaturvedi AK (2010). Beyond cervical cancer: burden of other HPV-related cancers among men and women. J Adolesc Health, 46, S20-6.
- Cheng JY, Meng CL, Chao CF, et al (1991). Human papillomavirus type related DNA and c-myc oncogene alterations in colon cancer cell lines. Dis Colon Rectum, 34, 469-74. https://doi.org/10.1007/BF02049931
- Cimino-Mathews A, Sharma R, Illei PB(2012). Detection of human papillomavirus in small cell carcinomas of the anus and rectum. Am J Surg Pathol, 36, 1087-92. https://doi.org/10.1097/PAS.0b013e3182549b6d
- De Vogel S, van Engeland M, Lüchtenborg M, et al (2006). Dietary folate and APC mutations in sporadic colorectal cancer. J Nutr, 136, 3015-21.
- Estrada P, Rojas-Atencio A, Zabala W, et al (2009). Frequency and clinicopathological associations of K-ras mutations in Venezuelan patients with colo-rectal cancer. Invest Clin, 50, 55-63.
- Georgieva S, Iordanov V, Sergieva S (2009). Nature of cervical cancer and other HPV - associated cancers. J BUON, 14, 391-8.
- Hinoi T, Akyol A, Theisen BK, et al (2007). Mouse model of colonic adenoma-carcinoma progression based on somatic Apc inactivation. Cancer Res, 15, 9721-30.
- Factors affecting sphincter-preserving resection treatment for patients with low rectal cancer vol.10, pp.2, 2015, https://doi.org/10.3892/etm.2015.2552
- Prevalência de câncer colorretal associado ao papilomavírus humano: uma revisão sistemática com metanálise vol.19, pp.4, 2016, https://doi.org/10.1590/1980-5497201600040009
- Human papillomavirus infection and colorectal cancer in the Chinese population: a meta-analysis pp.14628910, 2018, https://doi.org/10.1111/codi.14416