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Epidemiology and Molecular Biology Study of Risk Factors on Uigur and Han Cervical Cancer in Xinjiang

Author: LiuKaiJiang
Tutor: LiuJiWen
School: Xinjiang Medical University
Course: Occupational and Environmental Health
Keywords: Cervical cancer Risk factors HPV Parting The human telomerase gene Differential gene expression
CLC: R737.33
Type: PhD thesis
Year: 2008
Downloads: 787
Quote: 1
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Incidence rate of cervical cancer worldwide of female malignancies second place, according to the World Health Organization, International Agency for Research on Cancer (IARC) data show that in 2002 the global cervical cancer with 493,000 new cases and 274,000 deaths. Developed countries in the past few decades has been successful in reducing cervical cancer incidence and mortality. But in most developing countries, cervical cancer is still one of the most important malignancy in these areas. Despite the significant decline in the past 20 years, the mortality rate of cervical cancer in China but in some central and western regions of the morbidity and mortality of cervical cancer are far more than the national average. Also in Xinjiang, especially in southern Xinjiang Uygur women Cervical cancer is one of the high incidence of tumors in Xinjiang. Xinjiang Tumor Hospital, cases of Statistics found that: all kinds of malignant tumors in our hospital neutron cervical cancer accounted for a 18.9%, which is a phenomenon in other tumor hospital. But the difference between this national risk factors, not yet systematic epidemiological investigation, molecular biology research. Therefore, the Xinjiang cervical cancer, especially Uygur, Han cervical cancer features, pathogenesis, has been one of the focus of attention of health workers in Xinjiang. The current study suggests that the incidence of cervical cancer risk factors include three aspects: first, behavioral risk factors, biological factors, genetic susceptibility. Behavioral risk factors including premature sexual life, multiple sexual partners, early marriage, multiple births, poor sanitation, lack of knowledge of sexual health, immune function, and confusion spouse, smoking and oral contraceptives, where sex is cervical cancer of the most important co-factor. In recent years, the etiology of cervical cancer has made important progress. Now clear, papillary tumor virus (human papillomavirus HPV) genotypes that high-risk subtypes of HPV can cause cervical cancer or cervical intraepithelial neoplasia (CIN). More than 95% of the cases of cervical cancer and HPV infection, and different regions, different ethnic groups, different types of HPV mixed, caused by the progression of the disease and prognosis. The study also showed that the process of transformation of the cervical cells from dysplasia to cervical cancer is almost always accompanied by amplification of the long arm of chromosome 3. Wherein, to the most important relates to the gene may be a gene of the human telomerase gene (hTERC FIG located at 3q26.3). The amplification of the gene may prevent apoptosis, and thus can lead to tumors. Overseas studies have shown: detected by FISH 3q26 TERC gene found in CIN Ⅱ gene copy number increase accounted for 63%, the CIN III accounted for 76%, the number of tetraploid cells with cytology severity of the lesions and the TERC gene increase can be used as independent indicators predict high-grade lesions (HSIL) that the specific genome abnormalities of cervical lesion to invasive carcinoma of the conditions necessary. The incidence of cervical cancer, the development of a series of related genes result of joint action, to understand the genetic changes in the entire process of carcinogenesis, dynamic expression of all the genes in the cells that the various stages of cancer, need to study is not a or several genes, but the entire genome dynamic expression of many genes in various stages from normal to cancer. Looking Uygur, Han national cervical cancer related genes using gene chip technology can explore the different Uygur, Han cervical cancer gene profiling change, leading to differences in the pathogenesis of cervical cancer. Therefore, Uygur, Han cervical cancer risk factors, clinical epidemiology, HPV infection type do-spectrum detection and molecular biology research is very necessary. Objective: 1 from Clinical Epidemiology level, explore the Uygur, Han cervical cancer Features What What is the difference between the different incidence of risk factors. From the point of view of HPV infection, the understanding of the Xinjiang Uygur, Han patients with cervical cancer in women, the main type of HPV infection, and the proportion of each type of share of; looking for in addition to the previous study found that HPV 16, 18 type, high-risk subtypes; understand the Xinjiang Uygur and Han patients with cervical cancer in women, HPV infection mainly mixed type, and mixed type proportion; Through the above findings, the analysis of the reason why the Xinjiang Uygur cervical cancer high incidence of , the HPV infection type characteristics of influencing factors. From the perspective of gene amplification the TERC (human telomerase), aimed at understanding the Uygur, Han two nations cervical cancer patients after high-risk subtypes of HPV infection, the possible carcinogenic mechanism - TERC gene amplification explore the Uighurs of cervical cancer and Han cervical cancer pathogenesis level features and differences. From the point of view of the gene expression profile using gene chip technology find Uygur, Han ethnic cervical cancer related genes differentially expressed, and to explore whether the Uygur, Han cervical cancer genetic profile change different cause cervical cancer pathogenesis difference. Methods: a retrospective epidemiological survey, 1482 cases Uygur, Han hospitalized patients, 732 cases of the Uygur, Han patients with cervical cancer, 750 cases of cervical cancer patients in clinical epidemiology. Topics covered include general information, past medical history, sexual and reproductive history, contraceptive history, and smoking history, lifestyle and other aspects. (2) using the flow-through hybridization gene chip technology to detect 21 types of HPV subtype infection of 200 cases of the 732 cases of cervical cancer in Uygur and 200 Han Chinese patients with cervical cancer. HPV gene chips including 5 low-risk (HPV6, 11,42,43 and 44), 13 high-risk types (HPV 16, 18,31,33,35,39,45,51,52,56,58,59 68) and the Chinese population common subtypes (53,66, CP8304) genotype. 3 using fluorescence in situ hybridization (FISH) to detect the 400 cases of cervical cancer, 23 cases of Uighur and 22 Han Chinese patients with cervical cancer human telomerase (TERC) gene amplification. 4 chip containing 21,522 genes detected four cases of Uygur, Han cases of cervical cancer patients with cervical tissue gene expression profiles change. Results: 1. Retrospective epidemiological survey found that: patients with cervical cancer, compared with the Han, Uygur cervical cancer in young patients a high proportion of more advanced cases, the high rate of squamous cell carcinoma, low level of education, occupation basically peasants were the main, Uygur cervical cancer women's menstrual period of poor health, early marriage, early childbearing, the prolific distribution characteristics. Multivariate Logistic regression analysis found: Uighur women suffering from cervical cancer risk factors (OR value) Sort age for first childbirth, age at first marriage, number of pregnancies, menstrual timber, whether the family smoking and occupational factors. Han women suffering from cervical cancer risk factors (OR value) for the number of pregnancies, the husband to do the circumcision surgery, family members smoke, oral contraceptives, age at first marriage and education. 2 400 cases Uygur and Han patients with cervical cancer, HPV testing, the result is: (1) the Uygur, Han cervical cancer HPV infection spectrum. The Uygur cervical cancer in high-risk HPV subtypes sort: HPV16, HPV58, HPV18, HPV52 and HPV31; Han cervical cancer Sort: HPV16, HPV31, HPV58, HPV18 and HPV52. HPV58, HPV31, respectively, the second largest in the Uygur, Han cervical cancer reported in the literature. HPV58, HPV31 are the Uygur, Han cervical cancer are more vulnerable to the type of addition to HPV16. (2) Uighur cervical carcinoma multiplicity of infection of 43 cases, accounting for 21.83% of the HPV-positive patients; Han cervical carcinoma multiplicity of infection of 27 cases, accounting for l3.78% of the HPV-positive patients, both statistically significance. ③ HPV high-risk subtypes infection frequency in the Uygur, Han cervical cancer. Uighur cervical cancer, HPV16, HPV58, HPV18, HPV52 proportion of HPV-positive cervical cancer are 65.88%, 8.63%, 7.06% and 2.75%, respectively. Han cervical cancer, HPV16, HPV31, HPV58, HPV18 proportion of HPV-positive cervical cancer were 66.81%, 6.90%, 4.74% and 3.88%. 45 cases of Uygur, Han TERC gene detection of cervical cancer, the result is: Uygur TERC gene amplification rate of 86.96% Han cervical cancer amplification rate is 90.90%. TERC gene amplification in Uygur and Han cervical cancer mostly 3 times body (type 2-3 ,3-3) and 4 times the body (2-4 ,3-4 ,4-4 type ) amplification, a small part of more than six times the body or seven times body amplification. With the increased clinical stage, the TERC gene amplification of the Uygur, Han patients with cervical cancer have not increased significantly. Uygur, Han cervical cancer between subtypes of HPV infection, the the TERC average amplification is not statistically significant. Uygur cervical cancer TERC gene amplification multiples and Han statistically significant, and higher than the Han cervical cancer related to multiple infections Uygur patients with cervical cancer. Uigur, Han cases of cervical cancer patients differentially expressed genes spectrum detection, the result is: ① Uigur cervical cancer common differentially expressed genes more than four times the increase of a total of 378 (288, 90 down); common difference of 3 Han cases of cervical cancer gene expression more than four times the total of 549 (356 up-regulated, 193 down); Uigur cervical cancer and three cases of Han cervical cancer common differentially expressed more than 4 times the gene 166 raised. ② Uygur, Han cervical cancer have common differences in gene expression (mainly related to the proto-oncogenes, tumor suppressor genes, immune-related genes, cell signaling and transmission of protein, protein translation synthetic gene); But there are unique from the common differences gene expression. ③ the common different expression on four cases of Uighurs and Han cases of cervical cancer more than four times the 166 genes for data clustering analysis and found that cervical cancer inside a class individuals with similar characteristics, the individual characteristics of the different types difference. Conclusions: 1. Uygur and Han cervical cancer disease characteristics: age of onset of the former is smaller, squamous cell carcinoma constitutes more patients with advanced constituent ratio was significantly higher than Han. Logistic regression analysis showed that: Uygur, Han women suffering from cervical cancer have common behavioral risk factors such as age at first marriage, passive smoking, number of pregnancies; have their different risk factors. Sort of common risk factors in the two nations (or value), the role is different. And their different risk factors associated with the characteristics of all ethnic groups in the incidence of cervical cancer. Therefore, Uygur, Han incidence of cervical cancer, have obvious clinical epidemiology difference. Uighur cervical cancer behavioral risk factors that could cause a the Uighur women more vulnerable to exposure to HPV infection, including cervical cancer risk factors. HPV infection, Uygur, Han, the two nations have different infection spectrum; frequency of HPV high-risk subtypes in the Uygur, Han cervical cancer is also different; Uygur patients with cervical cancer have more high-risk HPV Asia type multiple infections; Uygur women infected with HPV on the more likely to develop into cervical cancer. Uygur and Han cervical cancer in the TERC gene amplification rate there is no difference, indicating that high-risk HPV subtypes of in telomerase carcinogenic mechanism, there is no difference between the peoples. Uygur, Han cervical cancer patients with clinical stage increased TERC gene amplification does not increase, either amplification of multiple cells or abnormal amplification ratio. Description TERC gene amplification is an early event in the incidence of cervical cancer in the two nations. Uygur, Han cervical cancer between subtypes of HPV infection, the the TERC average amplification is not statistically significant. But Uighur TERC gene of cervical cancer were significantly different average amplification ratio and Han, the main Uygur patients with cervical cancer, multiple infections is higher than the Han cervical cancer. Multiple HPV infection is more likely to result in the carcinogenic mechanism TERC gene amplification. Tip: Uygur patients with cervical cancer, multiple high-risk HPV subtype infection higher proportion of TERC gene amplification, may be one of the reasons Uygur cervical cancer incidence in the Han. In terms of differential gene expression, Uygur and Han cervical cancer are both the same differences expressed genes, and each with their own unique differentially expressed genes. Common genetic changes in the tumor incidence of cervical cancer, there are differences between peoples. Uygur, Han two nations shared differentially expressed genes contribute to a better understanding of the molecular mechanism of the development of cervical cancer, signal transduction pathways; expressed genes in each of the two nations unique common difference help to further our knowledge of cervical cancer in the pathogenesis of ethnic differences that may exist. In short, from clinical epidemiology of HPV infection, HPV carcinogenesis and cancer gene expression profile of different angles, different levels, different aspects of the Uygur, Han two ethnic characteristics of the disease and morbidity differences Some relevant factors. Concluded that: the Uygur, Han incidence rate is different due to different clinical-epidemiological risk factors, different high-risk HPV subtype infection spectrum, Uygur cervical cancer more multiple HPV infection, resulting in the TERC gene amplification. Uygur, Han cervical cancer both the same on the gene expression profiles of differentially expressed genes, has its own unique differentially expressed genes. These differentially expressed genes may be different Uygur, Han cervical cancer pathogenesis of different reasons.

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