| Ovarian cancer is one of the common gynecologic malignant tumors.Because of lack of early diagnosis method and effective treatment to this disease,ovarian cancer becomes a main disease that threatens women's health and life.While etiology of ovarian cancer is still unclear,some studies suggested follicle stimulating hormone (FSH),an important female sex hormone,not only stimulates the development of follicles in reproductive period,but also has a close relationship with ovarian cancer. FSH promotes the growth of tumor cells by the specific binding to the follicle stimulating hormone receptor(FSHR).There are many single nucleotide polymorphisms(SNPs) in FSHR gene.The Ala307Thr and Ser680Asn are the most common SNPs in the polymorphisms due to the linkage disequilibrium of exon 10.As a result,amino acid alteration related to the corresponding SNPs might affect the post-translational modifications of the FSHR protein,and hence the function of the receptor including FSH efficacy.Different genotypes of FSHR were related to different basal level of serum FSH.And the FSHR polymorphism might play a role in ovarian carcinogensis.Therefore,it's necessary to investigate the FSHR polymorphism.And the results might support the diagnosis and treatment of ovarian cancer at the genetic level in the future.To date,few studies concern the relationship between SNPs in FSHR gene and ovarian cancer.Neither do they achieve consistent conclusions.To further investigate their relationship,this study mainly consists of two parts.(1) Using the "polymerase chain reaction-restriction fragment length polymorphism"(PCR-RFLP) method to investigate how the SNPs in FSHR exon 10(Ala307Thr and Ser680Asn) impact the susceptibility of ovarian serous cancer.(2) Collecting and reviewing the ovarian serous cancer patients' medical information to estimate the relevance of the SNPs in exon 10(Ala307Thr and Ser680Asn) and the clinical prognosis of ovarian serous cancer. Part 1 SNPs of FSHR and the Susceptibility of Ovarian Serous CancerObjective:This study investigated the relationship between the SNPs in FSHR exon 10(Ala307Thr and Ser680Asn) and the susceptibility of ovarian cancer.Methods:This is a case-control study.In the analysis,ovarian tissues were collected from 35 patients with ovarian serous cancer and 22 people with normal ovaries as control.With the PCR-RFLP method,genotyping analyses were performed on Ala307Thr and Ser680Asn in FSHR exon 10.The results were analyzed by statistical test such as exact test,chi-square test,and non-conditional Logistic regression with two categories.Results:(1) The distribution of three genotypes of FSHR Ala307Thr(Thr/Thr, Ala/Thr and Ala/Ala) was statistically different between the patients with ovarian serous cancer and those with normal ovaries(P=0.004).The percentage of Ala carriers in case group was 97.1%,while it was 68.2%in control group.And the rate of Ala carry was significantly different in two groups after age-adjusted(P=0.022, OR=13.637,95%CI=1.466～125.850).(2) The distribution of three genotypes of FSHR Ser680Asn(Asn/Asn,Ser/Asn and Ser/Ser) was statistically different between ovarian serous cancer patients and normal ovaries group(P=0.004).The percentage of Ser carriers in case group was 68.6%,while it was 31.8%in control group.And the rate of Ser carry was significantly different in two groups after age adjustion(P=0.008, OR=4.964,95%CI=1.529～16.109).(3) The ratio of haplotype of Ala307-Ser680 was statistically different in two groups(P=0.031,OR=5.217,95%CI=1.040～26.165).Conclusion:Ala307Thr and Ser680Asn in FSHR exon 10 correlate with the susceptibility of ovarian serous cancer.307Ala carriers and 680Ser carriers were associated with significantly increased the risk of development of ovarian serous cancer.Moreover,the haplotype of 307Ala-680Ser was also associated with higher cancer risk. Part 2 Relevance of SNPs of FSHR and Prognosis of Ovarian Serous CancerObjective:This study investigated the relevance of the SNPs in FSHR exon 10 (Ala307Thr and Ser680Asn) and prognosis of ovarian serous cancer.Methods:The medical histories of patients with ovarian serous cancer and their follow-up information were reviewed so as to examine how the SNPs in FSHR exon 10(Ala307Thr and Ser680Asn) affect the prognosis of ovarian serous cancer patients. Statistical tests,including exact test,Kaplan-Meier test and Log-Rank test,were conducted to analyze how the SNPs at the two sites(Ala307Thr and Ser680Asn) affect recurrence,survival time,grades,staging,lymph node metastasis,and serum CA125 level in the initial diagnosis.Results:(1) The genotype distribution of Ala307Thr and Ser680Asn in FSHR gene exon 10 was of no significant difference in recurrent and non-recurrent group.And the ratio of 307Thr carriers and 680Ser carriers were also no statistically different in these two groups.(2) At the end of follow-up(Dec.31,2008),the mid-survival of the 35 patients with ovarian serous cancer was 42 months(8～79 months),and the 5 year survival rate was 40.0%.The genotype distribution of Ala307Thr and Ser680Asn in FSHR exon 10 was of no significant difference between life time over 5 years and less than 5 years.And 307Thr carriers and 680Ser carriers were not associated with the life time of ovarian serous cancer.(3) There was no statistical difference in different age of onset and staging of the genotype distribution of Ala307Thr and Ser680Asn in FSHR exon 10.And they had no association with serum CA125 level in initial diagnosis and lymph nodes metastasis.However,the distribution of Ala307Thr was statistically different in grade 3 and grade 1～2 group(P=0.02).The distribution of Ser680Asn had a differentiation trend along different pathologic grades(P=0.078).Conclusion:Ala307Thr and Ser680Asn in FSHR exon 10 had no significant correlation with prognosis of ovarian serous cancer patients.
|
PDF Full Text Request