Association Of Epithelial Ovarian Cancer And PR/AR Gene Polymorphism

Objective:To investigate the relationship between genetic susceptibility of epithelial ovarian cancer and the two single nucleotide polymorphism(SNP),+331G/A (rs10895068) and PROGINS (rs1042838) in progesterone receptor (PR) gene; to investigate the relationship between genetic susceptibility of epithelial ovarian cancer and the two short tandem repeat (STR) polymorphism,CAG (GDB:185508) and GGN (GDB:197027) in androgen receptor (AR) gene.Materials and MethodsSubjects:40patients with histological confirmed epithelial ovarian cancer were selected as case group,whose phases were I-IV according to the International Federation of Gynecology and Obstetrics (FIGO) stage and whose pathological classifications were well-differentiated Gl,moderately differentiated G2, and poorly differentiated G3according to the WHO. The ages of the patients range from30to77, with the average of52.13years old.48Han healthy women from the same region were selected as the control group. The ages of the patients range from30to70, with the average of49.48years old.Methods:1.Experimental methods:(1)Collected the peripheral blood and extracted high molecular weight genomic DNA;(2)Amplified sequences with polymerase chain reaction (PCR) and detected the product;(3) Purified the PCR products;(4)Sequenced the DNA.2. Genotyping methods:(1)+331G/A may have three genotypes:GG, GA and AA;(2) PROGINS may have three genotypes:CC, CA and AA;(3)CAG-A was the shorter one of the CAG biallelic, CAG-B was the longer one and CAG-M was the average of biallelic repeat numbers; CAG repeat numbers less than22were S-CAG,CAG repeat numbers more than or equal to22were L-CAG. Short group contained that dual alleles were S (CAG-A<22and CAG-B<22), and long group had the biallelic that at least one allele was L (CAG-B≥22);(4)GGN-A was the shorter one of the GGN biallelic, GGN-B was the longer one and GGN-M was the average of biallelic repeat numbers; GGN repeat numbers less than23were S-GGN,GGN repeat numbers more than or equal to23were L-GGN. Short group contained that dual alleles were S (GGN-A<23and GGN-B<23), and long group had the biallelic that at least one allele was L (GGN-B≥23).3.Statistical method:SPSS17.0was used for statistical analysis.(1)Direct counting method was used to calculate the genotype and allele frequency.Measurement data were expressed as mean±standard deviation (x±s).(2) χ2test was used to analyze the differences of STR distribution in case and control groups.Non-conditional logistic regression method was used to calculate the relative risk OR and95%CI;(3)Whether the genotype frequency distribution in two sets was in Hardy-Weinberg equilibrium was detected by χ2test.Whether the STR repeat length was correlated with ovarian cancer patients’ age was analyzed by the Pearson correlation analysis.T test was used to compare two sets of STR alleles repetitions.(4) One-way ANOVA analysis was used to analyze if the different classification of the case group was correlated with the STR repeat length in the AR gene;(5)T test was used to compare the correlation between different stages of patient group and the STR repeat length in the AR gene. Statistical analysis was undertaken with two-sided test. P<0.05was the test standard.Results:1.There was no significant difference between the case group and control group in the general situation of the patient, for example, age, age at menarche, pregnancy history, family history(P>0.05). 2.All the genotypes of+331G/A in PR were GG in both case and control groups.3.All the genotypes of PROGINS in PR were CC in both case and control groups.4.The distribution of CAG STR4.1The genotype frequencies of CAG in AR were in Hardy-Weinberg genetic equilibrium in case-control groups (P>0.05).The CAG repeat length and ovarian cancer patients’ age had no correlation according to Pearson correlation analysis (P>0.05)4.2There was no significant difference between the case and control groups about the CAG-A,CAG-B or CAG-M repetitions (P>0.05)4.3There was no significant difference between the case and control groups about the distribution of CAG short and long groups (P>0.05)4.4There was no significant relationship between different pathological grades of ovarian cancer patients and CAG repetitions in AR (P>0.05)4.5There was no significant relationship between different clinical stages of ovarian cancer patients and CAG repetitions in AR (P>0.05)5.The distribution of GGN STR5.1The genotype frequencies of GGN in AR were in Hardy-Weinberg genetic equilibrium in case-control groups (P>0.05).The GGN repeat length and ovarian cancer patients’ age had no correlation according to Pearson correlation analysis (P>0.05).5.2There was no significant difference between the case and control groups about the GGN-A,GGN-B or GGN-M repetitions (P>0.05)5.3There was a significant difference between the case and control groups about the distribution of GGN short and long groups(P<0.05).The risk who would get ovarian cancer with GGN short group increased by2.82(95%CI:1.00-7.97, P=0.03).5.4There was no significant relationship between different pathological grades of ovarian cancer patients and GGN repetitions in AR (P>0.05)5.5There was no significant relationship between different clinical stages of ovarian cancer patients and GGN repetitions in AR (P>0.05)Conclusions:(1)The GGN repeats was more shorter,then the risk of epithelial ovarian cancer was more higher.The longer GGN repeats in AR genes was protective factors for epithelial ovarian cancer.(2) The epithelial ovarian cancer may not be associated with PR gene polymorphism or the CAG STR in the AR gene.