| Objective: Cytochrome P450 are phase I enzymes in estro- gen metabolism, whose product catechol estrogen can induce cancer, and catechol-o-methyltransferase (COMT) make catechol estrogen to nontoxic products. Some studies indicated that the mutation of gene coding for CYP450 and COMT enzymes can lead to polymorphism resulting in the difference of enzymes activity. So these genes are correlated with the susceptibility to estrogen-dependent disorders. This study was designed to investigate the correlation of single nucleotide polymorphisms (SNPs), CYP1A1 Msp?, at codons 119G→T and 432C→G of CYP1B1 and at codon 158G→A of COMT to susceptibility of endometrial cancer in a population of Chinese North.Methods: The population-based case-control study included 122 endometrial cancer patients and 114 healthy controls. Genomic DNA was extracted by using proteinase K digestion followed by a salting out procedure. Polymorphisms of CYP1A1, CYP1B1 and COMT gene were analyzed by PCR- restriction fragment length polymorphism (RFLP) analysis.Statistical analysis was performed using SPSS11.5 software package. P<0.05 was considered significant for all statistical analyses. Hardy-Weinberg analysis was performed by comparing the observed and expected genotype frequencies in the control group using Chi-square test. Comparison of the CYP1A1, CYP1B1 and COMT genotypes and allelotypes distributions in cancer patients and healthy controls were performed by means of two-sided contingency tables using Chi-square test. The odds ratio (OR) and 95% confidence interval (CI) were calculated using an unconditional logistic regression model.Results:1 The comparison of the value of BMI in case with control groupTwo groups of BMI<25 and BMI≥25 were divided into case and control groups, the percentage was 71.1% and 28.9% in control, 49.2% and 50.8% in case. The percentage of BMI≥25 in case was obviously greater than that in control. By statistical analysis, there was significant difference between BMI≥25 and BMI<25 in two groups (χ2=11.482, P=0.001, OR=2.536, 95% CI=1.481~4.354).2 The comparison of CYP1A1 MspI T→C polymorphism in case with control group2.1 The distributions of CYP1A1 Msp I genotypes among hea- lthy controls did not significantly deviate from that expected by Hardy-Weinberg equilibrium (P>0.05). The frequency of wild genotype (T/T), heterozygous genotype (T/C), homozygous genotype (C/C) were 45.6%, 43.0%, 11.4% in control, and 32.7%, 50.8%, 16.5% in case. The frequency of heterozygous genotype and homozygous genotype in case were obviously upper than those in control, but no significant difference (P>0.05). The allele frequency of T and C were 67%, 33% in control, and 58%, 42% in case. The frequency of allele C in case was obviously upper than that in control. There was significant difference between the alleles of two groups (χ2=3.967, P =0.046). Contrast with wild genotype (T/T) genotype, merging heterozygous genotype (T/C) into homozygous genotype (C/C), the difference between case and control group was significant (χ2=4.048, P=0.044, OR=1.719, 95%CI= 1.014~2.915).2.2 According to menopause age, we detected the genotypes and allelotypes distributions of the CYP 1A1 MspI T→C SNP in the endometrial cancer patients, whose menopause ages were lower than fifty years, and did not find significant difference from that in healthy controls (P>0.05). In the patients whose menopause ages were more than fifty years, comparied with T/T genotype, merging T/C into C/C, there was significant difference between the patients and controls (χ2=5.794, P=0.016, OR=2.269, 95% CI=1.164~4.423); the frequency of allele T and C were 67.0%, 33.0% in control, 54.0%, 46.0% in case, the frequency of allele C in case was obviously upper than that in control. There was signifycant difference in two groups (χ2=5.291, P=0.015).2.3 According to BMI, in BMI<25, the frequency of allele T and C were 70.4%, 29.6% in control, 62.5%, 37.5% in case; in BMI≥25, the frequency of allele T and C were 59.1%, 40.9% in control, 54.0%, 46.0% in case. The proportion with mutation allele C in case was both upper than that in control, but no statistical significance (P>0.05).3 The comparison of CYP1B1 gene at codons 119G→T and 432C→G polymorphisms in case with control group3.1 The distributions of CYP1B1 119G→T and 432C→G codons genotypes among healthy controls did not significantly deviate from that expected by Hardy-Weinberg equilibrium (P>0.05). The allelotypes and genotypes distributions of CYP1B1 119 codon in case were not significantly different from that in healthy controls (P>0.05). But the frequency of homozygous genotype (T/T) in case was 8.2%, which was upper than that in control (3.5%), and the frequency of allele T in case was obviously upper than that in control. Contrast with wild genotype (G/G) when merging heterozygous genotype (G/T) into homozygous genotype (T/T), no significant difference were found between the case and control group (P>0.05)3.2 According to menopause age, at codon 119, the frequency of allele T was 29.7% in patients whose menopause ages were lower than fifty years, which was upper than that in control (20.2%), we found difference in the allelotypes distribution between the case and control groups (P=0.039); But there was no significant difference between the patients whose menopause ages were more than fifty years and controls (P>0.05).According to BMI, as BMI<25, the frequency of allele T was 25.8% in case, which was upper than that in control (21.2%), but there was no significant difference (P>0.05); the genotypes and allelotypes distribution in two groups were not significantly different as BMI≥25 (P>0.05).3.3 The allelotypes and genotypes distributions of CYP1B1 432 codon in case were not significantly different from that in healthy controls (P>0.05). Contrast with wild genotype (C/C) when merging heterozygous genotype (G/C) into homozygous genotype (G/G) at codon 432, no significant difference were found between the case and control group (P>0.05).3.4 According to menopause age, at codon 432, we did not find difference in the allelotypes and genotypes distributions between the cases and controls (P>0.05). According to BMI, the genotypes and allelotypes distributions at codon 432 in case were not significantly different from that in healthy controls (P>0.05).4 The comparison of COMT gene at codon 158 G→A polymorphism in case with control group4.1 The distributions of COMT gene at codon 158 genotypes among healthy controls did not significantly deviate from that expected by Hardy-Weinberg equilibrium (P>0.05). The frequency of homozygous genotype (A/A) in case was 4.9%, which was lower than 7.0% in comtrol; the frequency of A allele in case was lower than that in control, too, but there were no significant difference from that in healthy controls (P>0.05). Contrast with wild genotype (G/G) when merging heterozygous genotype (G/A) into homozygous genotype (A/A), we compared the case with control group and found no significant difference (P>0.05).4.2 Stratified by menopause age, when merging heterozygous genotype (G/A) into homozygous genotype (A/A), contrast with wild genotype (G/G), the distributions in the endometrial cancer patients whose menopause ages are lower than fifty years was significantly different from that in healthy controls (χ2=5.256, P=0.022, OR=0.422, 95%CI=0.201~0.882), and the allelotypes distribution too (χ2=7.395, P=0.007). However in case group the patients whose menopause ages were more than fifty years, the allelotypes and genotypes distributions were not significantly different from that in healthy controls(P>0.05).4.3 According to BMI, the frequence of A allele in control and case were 22.2% and 18.3% in BMI<25, 27.7% and 12.9% in BMI≥25, respectively. The proportion with mutation allele A in case was both lower than that in control, but no statistical significance (P>0.05).5 The comparison of the unification among genes of CYP1A1, CYP1B1 and COMT in case with control groupWe analyzied the unification among genes of CYP1A1, CYP1B1 and COMT by means of two-sided contingency tables using Chi-square test. When two or more genes mutation existed, the risk of endometrial cancer increased or not. There was no significantly difference (P>0.05). This indicated these genes had no unification in the risk of endometrial cancer. Conclusions:1 BMI correlated with the risk of endometrial cancer. The obesity individual increased the risk of endometrial cancer (OR=2.536). This indicated obesity was one of the predisposing factors in endometrial cancer.2 In CYP1A1 MspI polymorphism, the C allele may be the suspicious dangerous allele to endometrial cancer, the individual with one or more one C allele can increase the risk of endometrial cancer. Stratified by menopause age further, the data indicated that the risk of individual with C allele increased when menopause age was more later.3 CYP1B1 gene at codon 432 polymorphism can not increase the risk of endometrial cancer. Only codon 119 polymorphism was found different in the allelotype distribution between the patients whose menopause ages were lower than fifty years and controls. The discovery indicated codon 119 gene mutation may relate to the susceptivity of endometrial cancer when menopause age was early, but we can not confirm the risk.4 At codon 158 of COMT gene polymorphism, there was no association with the risk of endometrial cancer, but individual with A allele, the risk can degrade when menopause age was earlier.5 There was no the unification in genetic polymorphism of CYP1A1, CYP1B1 and COMT in the risk of endometrial cancer.
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