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Epidemiology And Etiology Study Of Female Breast Cancer And Cervical Cancer

Posted on:2007-06-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:N LiFull Text:PDF
GTID:1104360182992288Subject:Oncology
Abstract/Summary:PDF Full Text Request
IntroductionBreast cancer is the most commonly diagnosed cancer among women all o-ver the world, with an estimated 1,300,000 new cases and 273,000 deaths occurring every year. And the incidence is increasing recent years. Though China is the low - incidence country, the incidence of breast cancer was the first amomg the female malignant tumors in many lager citiesd remaining increasing.There are close correclation between occurring and development of breast cancer and many genes and proteins. It is a copmplex amd multi - phases course. The changes of genes and function of tyrosine kineas have been the focus of reasrches about breast cancer for many years. The Etk, which was discovered recently, was found that played important role on growth, differiation, atopsis and metastasis of tumor cells. The researches in cell lines in vitro have proved that Etk was related to breast cancer. However, the expression and function of Etk in human breast cancer tissues are not clear until now. It should be studied to complete the experimental data only in cell lines.On the other hand, though China was a low incidence country, there has been increasing of breast cancer incidence in female in northeast area of China. The incidence of breast cancer in Shenyang in 2000 was the first among the female malignant tumors. It clues us that the exposure to risk factors of local female was echanced. It is necessary to explore the etiology of breast cancer in northeast female from genetic and environment to provide the evidence to prevention of breast cancer at present.ObjectivesTo explore the etiology of breast cancer and investigate the relative risk fac-tor in northeast are of China. To provide the clues for comprehensive prevetion of breast cancer and evdince for screening in high risk population.Methods1. Protein and mRNA expression of Etk were determined by western blotting and RT - PCR in 107 breast cancer and normal breast tissues, as well as those of STAT3, ER - aand ER - (3in breast cancer. The correlation between Etk and STAT3, ER - aand ER - (3 was studied by bivariate correlation analysis.2. A case - control study was conducted on 620 cases with histopathological diagnosis and 620 matched controls, using method of Li - Mantel - Gart and Falconer to estimate the segregation ration and heritability. Conditional Logistic regression model, stratification analysis and interaction analysis were used to analyze the relative risk factors.Results1. The study on etiology of breast cancer1. 1 The correclation between Etk and clinical features: The expression of Etk in human breast cacner tissure and normal tissue were 0. 6047 ±0. 2282 and 0. 2798 ±0.1881 repectively. The expression of Etk in tumor was higher than in normal (t =2. 153, P < 0. 05). Etk high expression was related with lymph node metastasis and higher stages.1.2 The correclation between Etk and STAT3: The protein and mRNA expression for STAT3 in breast cancer were 0. 5033 ±0. 2049 and 0. 9879 ±0. 4685. Bivariate correlation analysis showed that protein and mRNA expression for STAT3 had significant correlation with STAT3 ( rs = 0. 825, P = 0.000;rs = 0.786, P= 0.000, respectively).1.3 The correclation between Etk and ER - a/ER - (3;The protein and mRNA expression were 0.8597 ±0.2845 and 0.9869 ±0.4215 for ER - a;and 0. 3472 ±0. 2017 and 0.4103 ±0.2510 for ER - |3. Bivariate correlation analy-sis showed that protein and mRNA expression for ER - Aand ER - (3 had significant correlation with Etk. Thus, expression of Etk had negtive correlation with ER-o/ER-p (r,= -0.732, P=0.0235).2. The study on epidemiology of breast cancer2.1 Heritability analysis of breast cancer family;The incidences of first degree relatives of probands and controls were 2. 44% (53/2168 ) and 0. 39% (8/2076) respectivelu. The RRvalue was 6.47. Segregation ration of female breast of was 0.11 ±0.011. The heritability of the first and second degree relatives were 45. 90 ±3. 869% and 14. 31 ± 12. 680% respectively.2. 2 9 factors (family history of breast cancer, family history of the other cancers, BMI > 24, menstrual disorder, abortion times > 2, non - lactation, psychological trauma, high level education and using hair dye) were associated with female breast cancer in univariate conditional Logistic regression model. Multivariate conditional Logistic regression analysis in total significant factors showed that the risk factors of female breast cancer would include family history of breast cancer, family history of the other cancers, BMI > 24, menstrual disorder , abortion times > 2, non - lactation, high level education and using hair dye. There is dose response between hair dye and breast cancer.Conclusions1. Etk may play an important role in development of breast cancer. Its function on breast cancer may be through activating STAT3 signal transduction pathway, then mediating expression of some genes in breast cancer. Etk may decrease expression of ER - a or promote that of ER - (3. It may also has both functions. According to the findings, considering the co - effectiveness of protein kinase and hemones will provide new eludes for management and treatment of breast cancer.2. The occurrence of female breast cancer in northeast results from multiple factors. Genetic factor plays an important role. The other risk factors are family history of breast cancer, family history of the other cancers, BMI > 24, menstrual disorder, abortion times > 2, non - lactation, high level education and usinghair dye. The prevention of breast cancer should pay more attention to these factors.IntroductionCervical cancer is the second most common cancer among women world -wide, with an estimated 493 ,000 new cases and 273,000 deaths occurring every year. Almost 80% of the cases occur in developing countries, where, in many regions, it is the most common cancer among women. There are about 45,000 new cases and 25,000 deaths occurring in China whose population is most a-mong the world. There has been a decreasing trend of cervical cancer death in China from the 70 's. However, the incidence of cervical cancer in younger women has increasd. Until today, there have not been the national cervical cancer screening programme and therefore we haven t had the data about distribution of HPV types based on population.Important progress in the study of the aetiology of cervical cancer has been made in recent years, and it is now clear that certain types of human papilloma-virus ( HPV) , called high - risk types ( HR - HPV) , are the necessary cause of cervical cancer and its precursors, the cervical intraepithelial neoplasias (CIN). Over 95% of cervical cancer cases are linked to genital infection of HPV.Currently, the best way to prevent cervical cancer is through regular cyto-logical screening and, when necessary, treatment of associated pre - cancerous lesions. However, due to the cost, implementation challenges, and complexity of properly screening and treating women in developing countries, this method has had only a limited impact in areas where it is most needed.Vaccines against HPV infections, on the other hand, have the potential to reduce the incidence of cervical cancer, particularly in low - resource settings and to be cost - effective. In fact, modelling studies suggest that the combining HPV vaccination and screening programmes may have the most impact on dis-ease control globally.Two candidate HPV vaccines, both protecting against the most common high -risk HPV types ( HPV 16 and 18) , and one also protecting against genital warts ( HPV 6 and 11), are in Phase III clinical trials and should enter the market in the near future ( Koutsky et al 2002, Harper et al 2004). Encouraging results from Phase II trials have shown that these vaccines protect against incident and persistent HPV 16 and 18 infections and associated pre — cancerous lesions in previously uninfected young women.With these two promising HPV candidate vaccines on the horizon, there are complex challenges ahead that must be overcome before the vaccine can be successfully introduced in China. We cannot be certain about whether the current vaccine candidates can offer the same degree of protection in every country or geographic area. Given that multivalent vaccines including additional HPV types are technically possible, it is essential to assess priorities for HPV types to be included in future vaccines. Furthermore, since HPVs are sexually transmitted, and prophylactic vaccines must be given prior to infection, it is important to acquire information on age of acquisition of HPV infection in population in China. Therefore, more local epidemiological data on HPV needs to be available to provide the data to vaccines and other relative prevention of HPV and cervical cancer.On the other hand, even if the vaccines introduced to our population, there still need about 10-20 years to play its role in all population prevention. Therefore , we must investigate the risk factors in high - risk area and evaluate the ef-ficiacy of different methods for cervical cancer screening, and provide the theoretical evidence to screening and prevention of cervical cancer in high risk population.ObjectivesTo investigate the age - specific prevalence of infection with 44 different types of HPV and other risk factors for high - risk HPV infection among women in high risk area. To provide the data to vaccines and theoretical evidence toscreening and prevention of cervical cancer in high risk population. To estimate the validity of 5 methods in cervical cancer screening.Methods-1. All mentally competent women aged 15-59 was selected randomly for the study. The questionairy of epidemiology was filled and then input into computer twice for checking.2. HC - II was used to detect the high - risk HPV.3. PCR, ELA and Southen blotting were used to dectect the HPV types.4. Youdens index was used to estimate the validity of 5 methods in cervical cancer screening.Resuelts1. The average age of subjects was 40. 83 ± 10. 73 years old. Infection rate of the high - risk HPV was 15. 97%. The most high - risk HPV types in Yangcheng were 16 and 58.2. The risk factor of high -risk HPV infection in local area was the health custom.3. The study shows that the vadility of HPV DNA detect test is best.Conclusions1. The study was performed under double - blind. Form the results, we can conclude that the high - risk HPV infection occur mainly before 25 years old and after 35 years old. HPV 16 and 58 play an important role in infection in local area. The validity of present vaccines is not good enough for cervical cancer prevention in local area.2. Health custom is the maily effective factor of HPV infection in local women. Education about the change of health custom, increasing of health awareness and enhaceing the sanitary institution will play important role in HPVinfection in the area.3. Though HPV DNA detect test is best for cervical cancer screening, VILI are more suitable in local area owing to the low - resource settings and low income.
Keywords/Search Tags:Etk, heritability, breast cancer, risk factor, HPV, Types, Cervical cancer, Risk factor, Screening
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