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Folate Metabolism Enzyme Genes Rfc-1, The Mtrr Polymorphism And Hpv16 In Cervical Cancer Research

Posted on:2008-07-28Degree:MasterType:Thesis
Country:ChinaCandidate:J J DiFull Text:PDF
GTID:2204360215988418Subject:Epidemiology and Health Statistics
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Objective:Cervical cancer is one of the most common malignancies in the worldwide.It is second to breast cancer as the most common malignancies in incidence.To explore the relationship of folate acid and the polymorphism of MTRR,RFC-1 with cervical cancer risk which would offer some new evidences for the etiology of cervical cancer.Methods:A hospital-based case-control study was conducted in Shanxi Tumor Hospital from Jane 2005 to June 2005.The study included 107 women newly diagnosed by pathology of cervical cancer and 107 control of hysteromyoma.The case were frequency-matched with control by age(±3 years).All participants required Shanxi resident,Han people,and people who had cerebrovascular disease,haemolyticus disease,digestive system disease,VitB supplement within3 months lately and other dysplasias were considered ineligible for study.A standardized questionnaire was used to screen risk factors of cervical cancer,including demographic and lifestyle information,sexual and reproductive history and oral contraceptives using.Blood samples were drawn in before breakfast,serum folate was measured using radiobinding assay, HPV16 was gained by PCR,Genotyping for the MTRR and RFC-1 polymorphism was analyzed by PCR-RFLP.Statistical analysis was conducted by SPSS 11.5 software.Results:(1)Occupation,incomes,education background,cigarette smoking,menopause, age at first sexual intercourse and parity are related to cervical cancer risk.(2)HPV16 infection rate is significantly higher in case than it in control(56.07%and43.93%)the odds ratios is 3.25(95%CI:1.74-6.08).(3)Serum folate in case is significantly lower than it in control,by Quartile,using women of highest serum folate level as reference category,there was a dose-responded relationship between cervical cancer and serum folate(χ~2=12.57,P=0.00).(4) Folate and HPV16-infected showed a significant interaction in the development of cervical cancer(Waldχ~2=4.05,P=0.04),OR=0.30(95%CI:0.09~0.97).(5)All genetypes between case and control were tested by Hardy-Weinberg balance.MTRR gene's frequencies of AA,AG,and GGgenotype were 46.73%,42.99%,10.22%,respectively in case and were 50.47%,41.12 %å'Œ8.41%,and there is no relationship between them.(χ~2=0.40,P=0.82).In the analysis of MTRR gene and folic acid,when taking sufficient folic acid and(AA+AG)as reference,only 66GG existed could increase the risk of cervical cancer(OR=1.79,95%CI:0.41~7.70),only folic acid lack existed could increase the risk of cervical cancer(OR=2.50,95%CI.1.39~4.50),when both lack of folic acid and 66GG existed,the risk for cervical cancer was higher(OR=2.97, 95%CI:0.66~13.40).(6)About the RFC-1 gene there is distinguished difference between case and control,well the difference of them in gene-type is nonsense,which is tested by Hardy—Weinberg balance.(7)RFC-1 polymorphism is associated with cervical cancer,and the GG homozygosis mutation take a significant role when taking AA gene type as the reference.(8)In the analysis of RFC-1 and folic acid,when taking sufficient folic acid and(AA+AG)as reference,only 80GG existed could increase the risk of cervical cancer(OR=3.13,95%CI: 1.01~9.85),only folic acid lack existed could increase the risk of cervical cancer(OR=2.70, 95%CI:1.42~5.13),when both lack of folic acid and 80GG existed,the risk for cervical cancer was the highest(OR=3.83,95%CI:1.62~9.05).(9)In the analysis of RFC-1 and MTRR gene,when taking both(AA+AG)as reference,only 80GG existed could increase the risk of cervical cancer(OR=2.00,95%CI:1.01~4.00),only 666G existed could increase the risk of cervical cancer(OR=1.18,95%CI:0.33~4.25),when both 6666 and 8066 existed,the risk for cervical cancer was the highest(OR=2.37,95%CI:0.42~13.30).Conclusions:(1)Peasant,smoking,multiparty,earlier age at first intercourse were associated with increased risk of cervical cancer,Menopausal,higher education degree,higher incomes were the protect factors of cervical cancer.(2)HPV16 infection was the etiology associated with the development of cervical cancer.(3)Regardless of high-risk HPV16 infection and other risk factors,Low serum folate status might be a risk for cervical cancer.(4) serum folate had effect with HPV16 infection in the development of cervical cancer.(5)The mutant type homozygote of RFC-1 A80G was a risk factor of cervical cacer.The women who had RFC- 1 80GGgene type were induced to develop to cervical cancer.(6)Although there is no statistic association between MTRR gene A66G polymorphism and cervical cancer,a weak and nonsignificant relationship exits between mutant type homozygote of MTRR gene A66G and cervical cancer.(7)There is a weak interaction between folic acid and RFC-1 polymorphism.
Keywords/Search Tags:Cervical cancer, Human papillomaviruses16, Folate, MTRR Polymorphism, RFC-1 Polymorphism
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