Overview

This dissertation, Single Nucleotide Polymorphism in the Coding Sequence of Follicle Stimulating Hormone Receptor and Susceptibility to Ovarian and Endometrial Cancer by Chongqing, Yang, 楊重慶, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled SINGLE NUCLEOTIDE POLYMORPHISM IN THE CODING SEQUENCE OF FOLLICLE STIMULATING HORMONE RECEPTOR AND SUSCEPTIBILITY TO OVARIAN AND ENDOMETRIAL CANCER submitted by YANG Chong Qing for the degree of Master of Philosophy at the University of Hong Kong in August, 2004 Epidemiologic studies suggested that ovulation was associated with the pathogenesis of ovarian cancer and the follicle-stimulating hormone (FSH) played important role in follicular development. Recent studies on the biological effect of FSH revealed that FSH could initiate the growth and malignancy transformation of ovarian and endometrial cell lines. The FSH receptor (FSHR) is present at the membrane of a variety of cells, including ovarian surface epithelial cells. Single nucleotide polymorphisms (SNPs) Thr307Ala and Asn680Ser were two most important variations with respect to biological potency among seven documented SNPs in the coding region of the FSHR gene. They are nonsynonymous and can affect the efficacy of FSHR leading to alteration in biological response of the target cells after stimulation of FSH. We hypothesized that the carcinogenic role of FSH-FSHR might be affected by the SNPs of Thr307Ala and Asn680Ser. The aim of this study was to investigate the association of these SNPs with the risk of ovarian and endometrial cancers. Genotyping of these two SNPs was performed based on the methods of polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLPs). The patients of ovarian cancer (202 cases) and endometrial cancer (147 cases) were age-matched with control subjects (266 and 376 cases respectively) with ovaries or uterus removed due to benign conditions. Hardy-Weinberg Equilibrium was assessed in control subjects. The haplotype and linkage disequilibrium of these two SNPs were analyzed using computer-assisted methods with the softwares of Arlequin and 2LD. Our results showed that these two SNPs were in Hardy-Weinberg Equilibrium and linkage disequilibrium. The alleles of Ala307 and Ser680, the carriers of Ala307 and Ser680, and the resulted haplotype of Ala307-Ser680 (ORs=1.477, 95%CI=1.106-1.974) were associated with the higher risk of ovarian cancer, especially for the subtypes of mucinous and serous (ORs=1.855, 95%CI=1.313-2.622 for Ala307-Ser680), but not for those of endometrioid and clear cell types. Although the risk association was not observed in genotypes, alleles, carriers of these two SNPs in endometrial cancer, haplotype of Ala307-Ser680 was still found to be associated with higher risk of endometrial cancer (ORs=1.502, 95%CI=1.117-2.019), which suggested these two SNPs may have synergetic effect in the process of carcinogenesis. Moreover, two other minor haplotypes of Thr307-Ser680 (ORs=0.192, 95%CI=0.059-0.626) and Ala307-Asn680 (ORs=0.490, 95%CI=0.271-0.885) had been observed to be associated with the decreased risk of endometrial cancer or have this tendency. It is possible that the differences in the frequency of these two SNPs in different ethnic groups may contribute to the different incidence of ovarian and endometrial cancer in different populations. We concluded that SNPs Thr307Ala and Asn680Ser could synergistically affect the susceptibility of ovarian and endometrial cancer.

Full Product Details

9781361205662

Table of Contents

Reviews

Author Information

Tab Content 6

Customer Reviews

Recent Reviews

Countries Available