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Epidemiology And Molecular Biology Study Of Risk Factors On Uigur And Han Cervical Cancer In Xinjiang

Posted on:2009-03-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:K J LiuFull Text:PDF
GTID:1114360242499611Subject:Occupational and Environmental Health
Abstract/Summary:PDF Full Text Request
According to the International Agency for Research on Cancer (IARC) ,cervical cancer is the second most common cancer among women world- -wile,with an estimated 493,000 new cases and 273,000deaths occurred in 2002. In the past few decades, developed countries had succeeded in reducing morbidity and mortality of cervical cancer. However, in many developing countries, cervical cancer screening for initiating and conducting the scheme conditions related facilities is not yet perfect or can not meet demand. Cervical cancer is still the most important cancer of these areas. While in the past 20 years, there has been a great decreasing trend of cervical cancer death in China, but,incidence and mortality rates of cervical cancer have far exceeded the country's average level in some central and western areas. Also in Xinjiang, especially in the southern part of Xinjiang , cervical cancer of Uigur women is one of the high incidence of tumors. It was found by the affiliated tumor hospital of Xin Jiang Medical University that: cervical cancer (18.9%) was the first one in each type of tumoramong women .The phenomenon could not be found in the other national cancer hospitals. There was a significant difference between the incidence of Uigur with cervical cancer and Han patients. However, the differences of risk factors between two nations has not yet been done by systematic epidemiological investigations, molecular biology research and so on in the field of work. Therefore, the research of Xinjiang cervical cancer, especially, studies of characteristics of incidence and different pathogenesis of Uigur and Han patients has been paid more attention as one of focuses in Xinjiang.On the basis of the current studies, the risk factors of incidences of cervical cancer include the following three aspects: First, behavioral risk factors, the second is the biological factors, the third is genetic susceptibility. Among them, behavioral risk factors include sexual life prematurely, multiple sexual partners, early marriage, multiple births, poor sanitation, lack of health knowledge, immunocompromised, the spouse of confusion, smoking and oral contraceptives and so on. In which, the sexual behavior is the most important supplementary factors which cause cervical cancer. In recent years, the etiology research of cervical cancer has made important progress. At present, it has become confirmed that some genotypes of human papilloma virus (human papillomavirus,HPV), such as high-risk HPV can cause cervical cancer or cervical intra-epithelial neoplasia (CIN). More than 95% of cervical cancer cases are related with HPV infection, but also there are differences bewteen different regions and different ethnic on mixing different types of HPV so that the condition and prognosis caused by the condition and prognosis are also different. The research also showed that in the process of the cervical cells which changed from atypical abnormal development to cervical cancer with almost all of the long arm of chromosome 3 was amplified. Among them, the most important related to the gene might be human chromosome telomerase (hTERC gene map in 3 q26.3) gene. The amplification of the gene may prevent apoptosis, which can lead to a tumor. Overseas studies showed: they used three-color FISH probes on cervical cells smears to detect 3 q26 TERC gene, found in CIN2,there was 63% copy number increased . The percent of increase in gene copy number of CIN3 was 76%. Tetraploid cell and TERC Gene increased with the increase of serious level of cytological pathological changes. It can be an independent indicators of predicted high lesions (HSIL). So it can be estimated that specific genomic abnormal change is necessary condition which makes cervical precancerous change to invasive carcinoma. The occurrence and development of cervical cancer is results of a series of related genes. It is necessary to understand the entire process of carcinogenesis of the gene modification, so the need to be studied is not one or a few genes , but the entire genome from normal to cancer in various stages of thousands of gene expression in the dynamic changes. Using gene chip technology can search different related gene to analyze differences of cervical cancer-changing spectrum and pathogenetic disparity which cause uterine cervix cancer. Therefore, it is essential to do research of clinical epidemiology survey, detection of HPV infection type spectra and molecular biology on risk factors of incidence of cervical cancer between Uigur and Han patients.Objectives:1. To approach differences of morbidity characteristics and different risk factors of different incidence between Uigur and Han cervical cancer from the clinical epidemiology level in Xiniiang.2. From HPV infection to comprehend the major types of Uigur and Han cervical cancer patients in Xinjiang region, as well as the proportion of each type; Find other high-risk subtypes besides the HPV16, 18 which were found before ; Understand in the Xinjiang region, Uigur and Han cervical cancer patients with HPV infection of the main mixed types and proportion of various other mixed types .Through the above results , the reason of Xinjiang Uigur high incidence of cervical cancer is whether there is a type of HPV infection characteristics of the influencing factors.3. From TERC (human telomerase chromosome) gene amplification perspective to understand nation-two patients with cervical cancer in high-risk HPV infection subtype. Use the possible carcinogenic mechanisms -TERC gene amplification to discuss the pathogenesis characteristics and differences of the Uigur and Han cervical cancer on this level.4. Use gene chip technology searched different related gene to analyze differences of cervical cancer-changing spectrum and pathogenetic disparity which caused uterine cervix cancer by differentially expressed genes.Methods:1. Through the form of retrospective clinical epidemiological questionnaire for 1,482 cases of Uigur and Han patients, there were 732 cases of Uigur and Han patients with cervical cancer, 750 cases of patients with non- cervical cancer were studied by clinical epidemiological investigation. The survey includes general information on past history, sexual and reproductive history, the history of contraception and smoking history, living habits, and so on.2. Use channelization hybridization gene chip technology detected 21 kinds of HPV subtypes on the 200 cases of Uigur cervical cancer and 200 cases of Han cervical cancer of the above 732 examples of uterine cervix cancer, including 5 kinds of low-risk type (HPV6, 11,42, 43 and 44), 13 kinds of high-risk (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) ,the common Chinese subtype (53,66, CP8304)and so on .3. Use fluorescence in situ hybridization (FLISH) detected the above 400 cases of cervical cancer, understand the situation of human chromosome telomerase (TERC) gene amplification on 23 cases of Uigur patients and 22 cases of Han patients.4. The gene-chip which contained 21,522 strips was used to detect changes of differentially expressed genes on four cases of the Uigur and Han three cases of cervical cancer in patients with cervical tissue .Results:1. It was found that through retrospective epidemiological survey: compared to Han patients with cervical cancer, Uigur young proportion is higher than the Han nationality, higher ratio of squamous cell carcinoma ,educational constituent ratio than to a mainly illiterate, Occupational low basically to farmers, multiple factor Logistic regression analysis showed that: risk factors of Uigur women suffering from cervical cancer (OR by value) included by turn :the initial delivery of age, age at first marriage, the number of pregnancy, article for menstruation, family factors such as smoking and occupational . The risk factors of Han Chinese women suffering from cervical cancer (OR by value) were the number of pregnancy, whether or not to do foreskin about her husband, family smoking, oral contraceptives, the first marriage age and education level.2. Through the HPV detection of 400 cases Uigur and Han patients with cervical cancer:â‘ The HPV infection spectrum of Uygur, Han cervical cancer were different. The subtypes of Uigur cervical cancer in high-risk HPV by turn were HPV16, HPV58, HPV18, HPV52 and HPV31; The subtypes of Han were HPV16, HPV31, HPV58, HPV18 and HPV52. HPV58, HPV31 ranked second in Uigur, Han cervical cancer.It is different with the reported. HPV58, HPV31 are likely more susceptible types besides HPV16 in Uigur and Han cervical cancer.â‘¡The cases of Uigur cervical cancer in multiple infections were 43 ,which was 21.83% in HPV-positive patients; The cases of Han cervical cancer in multiple infections were 27 ,which was 13.78% in HPV-positive patients. Compared with each other, there was a statistical difference.â‘¢The infection frequency of HPV high-risk subtypes was different between the Uigur and Han cervical cancer. The proportion of HPV16, HPV58, HPV18, HPV52 of Uigur cervical cancer in the HPV-positive cervical cancer were 65.88 %, 8.63 %, 7.06 %and 2.75 %.The proportion of HPV16, HPV31, HPV58, HPV18 of Han cervical cancer in the HPV-positive cervical cancer were 66.81%, 6.90%, 4.74% and 3.88%.3. Through 45 cases of cervical cancer-TERC gene detection: the TERC gene amplification rate of Uigur cervical cancer was 86.96% and amplified cervical cancer rate of Han uterine cervix cancer was 90.90%. The majority types of TERC gene amplification in the Uigur and Han were three ploid (2-3type,3-4type)and 4 ploid (2-4 type, 3 - 4 type,4 - 4 type) amplification and a small part of amplification were significant ,or six times of more than seven times in amplification. With the increases of clinical stage,the TERC gene amplification of Uygur and Han cervical cancer patients had not increased significantly. Among the infections of each HPV subtypes,there were no statistical differences on average multiples of TERC gene amplification. But there were statistical differences on the total of Uigur TERC gene amplificated multiples between Uigur and Han cervical cancer.It was mainly related with higher rate of multi-infection in Uigur cervical cancer patients ,compared with Han patients.4. Through four cases of Uigur and Han three cases differentially expressed genes in patients with cervical cancer detection spectrum:â‘ The common genes of above 4 ploid in 4 cases of Uigur cervical cancer differentially expressed genes were total of 378 strips(288 up, 90 down); The common genes of above 4 ploid in 4 cases of Han cervical cancer differentially expressed genes were total of 549 (288 up, 90 down) total of 549 strips (356 increase, 193 down); The common genes which were above 4 ploid of differentially expressed genes in four cases of Uigur cervical cancer and three cases of Han cervical cancer were the total of 166 up.â‘¡Uigur and the Han ethnic cervical cancer had common differentially expressed genes (mainly related oncogene , and anti-oncogene, immune-related genes, cell signaling and transmission of protein, protein translation of genes), but each of which has its own unique differentially expressed genes . Found that the occurrence of cervical cancer had common genetic changes and the difference between the nations.â‘¢It was studied by data fuzzy grouping analysis for 166 strips genes of above 4 polid of common differentially expressed genes in four cases of Uigur cervical cancer and three cases of Han cervical cancer ,found that the the internal individual of each kinds of cervical cancer on characteristic had similarities, but there were greater differences among the individual characteristics of different types.Conclusions:1. There are differences between Uigur and Han cervical cancer on characteristics of incidence of cervical cancer: age of onset is young, constituent ratio of Uigur patients with earlier cervical cancer is obviously lower than Han patients. And through multiple factor Logistic regression analysis , Uigur and Han patients with cervical cancer had common risk factors such as the first marriage age, second-hand smoking and the number of pregnancy. And they also had different risk factors. The sorts of common risk factors were different between them (OR by value).It showed that their effects were also different. Each different risk factors was related with characteristics of invasion of each ethnical cervical cancer. Incidence rate of Uigur uterine cervix cancer is great higher than Han .It has obviously different characteristics of clinical epidemiology Those characteristic may make Uigur women contacted with some risk factors of cervical cancer including HPV infection more easily.2. On HPV infections, subtypes of High-risk HPV in Uigur cervical cancer appeared higher frequenctly.What's more,Uigur and Han had different infection spectrums.Uigur patients with cervical cancer had more multiple high-risk HPV infection. This made Uigur women infected with HPV to cervical cancer more easily.3. There was no differences between Uigur and Han cervical cancer on TERC gene amplification .In the high-risk HPV subtypes that telomerase carcinogenic mechanism, there was no differences among the people.With the increase of clinical stages, whatever multiple of TERC gene amplification or abnormal cell proliferation rate. TERC gene amplification might be the incidence of early gene on carcinogenesis.There were statistical differences on the total of Uigur TERC gene amplificated multiples between Uigur and Han cervical cancer.It is mainly related with higher rate of multi-infection in Uigur cervical cancer patients ,compared with Han patients..Therefore, it is illustrated that the multiple of HPV infection on carcinogenic mechanism leads to TERC gene amplification more easily.4. On differentially expressed genes, both Uigur and Han with cervical cancer had the same differentially expressed genes, each of which had its own unique differentially expressed genes. It illustrated that cervical carcinogenesis had common changes of tumor genes and also had ethnical differences. It is helpful for us to get further understanding on the molecular mechanism of development and signal transduction pathway for study of common differentially expressed genes between them. The study of typical differentially expressed genes of each nations can also help us to know that it may have the ethnic differences on the pathogenesis of cervical cancer.This study includes some relevant factors of morbific characteristics and differental morbility from clinical epidemiology,different parts, different levels and in different aspects of HPV infection,HPV carcinogenic mechanism of carcinogenesis and differences in gene expression after canceration between Uigur and Han. Come to the conclusion that: The differences of incidence rate between Uigur and Han caused by different risk factors of clinical epidemiology and different high risk subtype infection spectrum of HPV . Uigur cervical cancer had more multiple HPV infection, which led to the TERC gene amplify obviously. Finally, after cancerization, there are the same differentially expressed genes of cervical cancer on gene expression spectra, each of which has its own unique differentially expressed genes. Uigur and Han with cervical cancer both had the same differentially expressed genes, each of which had its own unique differentially expressed genes.Those distinction of differentially expressed genes may be one of reasons of pathogenesy of cervical cancer.
Keywords/Search Tags:cervical cancer, risk factor, HPV (human papilloma virus), subtype, TERC (Human Telomerase Gene), differentially expressed genes
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