Human Papillomavirus Genotypes and the p53 Codon 72 Polymorphism in Cervical Cancer of Northeastern Thailand

Abstract

Cervical cancer is the most common female cancer in Northeastern Thailand (2) and is still the highest cause of mortality in females of this region (23). Our previous study has indicated that sexual behavior and smoking were risk factors for this cancer (19). In addition, we must pay attention to human papillomavirus (HPV) infection that is the most critical risk for cervical cancer (9, 18).HPV comprises so many strains; they are classified into a low-risk group (such as ) and a high-risk group (such as . Cervical infection with the certain subtypes of HPV, particularly of the high-risk group, closely correlates with the development of cervical cancer (17,18,26).Participation of the p53 alterations including somatic mutations and germline polymorphisms in tumor development has been well documented (1,25). Codon 72 polymorphism (Arg/Pro allele) of p53 is widely distributed in various human populations (5). One of the striking features of this polymorphism is efficient degradation of Arg type of p53 by HPV E6 oncoprotein and carriers of Arg type of p53 were about seven times more susceptible to cervical cancer (20). The high risk type of p53 with Arg for cervical cancer was supported by several epidemiological studies on European subjects (12,24,25). However, studies on British (16), Japanese (13), Korean (7) and Black South African (15) subjects denied the risk. The distribution of the p53 codon 72 genotype varies according to ethnicity (5) and it is rather difficult to generalize from the conclusion obtained for a given population. The relationships between the p53 polymorphism and susceptibility to HPV infection as well as development of the cervical cancer is still unclear. In Northeast Thailand, although high incidence of cervical cancer is present, very limited data for HPV infections are available (4,10,11,21,22 Abstract: Human papillomavirus (HPV) infection including sub-strain identification was studied in patients with squamous cell cervical cancer (SCCA) in Northeastern Thailand. Subjects were 90 cases of SCCA and 100 healthy controls. Prevalence of high-risk group of HPV infection in the controls and the SCCA patients were 13.0% and 86.7%, respectively. The HPV infection significantly increased the risk for cervical cancer 43.5-fold (95% confidential interval: 17.5-110.6; P<0.00001). Among HPV carrier patients with SCCA (n‫,)87؍‬ HPV-16 was also prominent (70.5%) followed by HPV-18 (23.1%). There was no statistical difference in the subtype distribution between the SCCA and the control groups. There was no significant association between genotype distribution of the p53 codon 72 polymorphism and HPV infection. HPV infection was confirmed as a critical risk factor for cervical cancer development in Northeast Thailand. Since polymorphism of the p53 itself as well as in combination with HPV infection may not be a genetic risk for cervical cancer, much attention should be paid to other risk factors such as sexual behavior and smoking.

Human Papillomavirus Genotypes and Cervical Cancer in Northeast Thailand

“…As for the prevalence of the various types of HPV, the general experience is the high prevalence of HPV-16 followed by HPV-18 (Chichareon et al, 1998;Settheetham-Ishida et al, 2005;Suthipintawong et al, 2011); however, our results indicated a rather high prevalence of HPV-58 (17.8%) in SCCA. HPV-58 is not rare in Asian women with normal cervical cytology; its prevalence being <1% in Thailand, Vietnam, Japan and Korea (Domingo et al, 2008;Konno et al, 2008) and 1~2% in Taiwan and China (Shi et al, 2008;Tay et al, 2008).…”

Risk Factors for Cervical Cancer in Northeastern Thailand: Detailed Analyses of Sexual and Smoking Behavior

“…Among healthy women, an HPV infection was able to clear within 1-2 years (Klug et al, 2009;Schiffman et al, 2007) and <1% of HPV-positive women would go on to develop cervical cancer (Josefsson et al, 2000;Nagpal et al, 2002). The current report indicates that the involvement of other factors such as sexual behavior, personal and partner smoking habits and genetic backgrounds are likely co-factors with HPV for an increased risk of developing cervical cancer (Settheetham-Ishida et al, 2004;Settheetham-Ishida et al, 2005;Au et al, 2007;Almonte et al, 2008).…”

“…The prevalence of HPV infection among patients (85.9%) and controls (14.1%) seems higher compared to the previous study reporting the positivity rate 12% and 78% for the patients and controls, respectively. This may be attributable to the detection of only high risk HPV infections in the latter study (Settheetham-Ishida et al, 2005), a further HPV-typing will clear the gap of the prevalence. HPV infection was also detected in the controls indicated that not all of the HPV-infected women developed cervical cancer.…”

Analysis of a p53 mutation associated with cancer susceptibility for biochemistry and genetic laboratory courses

“…The following materials are necessary to analyze the p53 mutation: laboratory coats, gloves, Pipetman (model numbers p2, p20, p200, and p1000), sterile and UV-irradiated pipette tips, sterile stings, thermocycler with accompanying PCR tubes, a gel electrophoresis power unit, polyacrylamide gel apparatus consisting of glass plates (20 cm 3 20 cm 3 0.5 mm), clamps, tape, and spacers, Whatman FTA cards, Taq polymerase (Applied Biosystems, USA), dNTPs (Invitrogen, USA), primers: (20 lM oligo p53 5 0 CCCGGACGATATTGAACA 3 0 forward; 5 0 AGAAGCCCAGACGGAAAC 3 0 reverse [13], 25 mM MgCl 2 (Sigma), acrylamide, and bisacrylamide (Sigma).…”

“…The primers used were as follows: 5 0 CCCGGACGATATTG AACA3 0 forward; 5 0 AGAAGCCCAGACGGAAAC 3 0 reverse [13].…”