Correlation Between Folate Level,MTHFR Gene And MTRR Gene Polymorphisms With Pathological Characteristics Of Cervical Squamous Cell Carcinoma

Objective: To investigate the correlation between serum and dietary folic acid levels,MTHFR and MTRR gene polymorphisms and pathological features of cervical squamous cell carcinoma.Methods: A total of 105 cases were collected from December 2019 to December 2020 in the gynecological clinic or gynecological ward of the Affiliated Hospital of Zunyi Medical University,and all were diagnosed pathologically.Among them,control group 1(chronic cervicitis and / or cervical low-grade squamous intraepithelial lesions),control group 2(high-grade squamous intraepithelial lesions of the cervix),research group(squamous cell carcinoma of the cervix),there were 35 cases in each group above.Chemiluminescence method was used to detect the folic acid levels of serum samples in each group;with3.1ng/m L as the cut-off value,they were divided into normal folic acid levels and folic acid deficiency groups.The dietary folic acid intake of the patients was investigated by food frequency method.According to the recommended folic acid intake in China,those with less than 400 μg DFE/d were assigned to the group with insufficient dietary folic acid and those with more than 400 μg DFE/d were assigned to the group with normal dietary folic acid.PCR-fluorescent probe method was used to detect the expression of C677 T locus,A1298 C locus of MTHFR gene and A66 G locus of MTRR gene in serum samples of each group.Results: 1.There were significant differences in age,number of pregnancies and the infection rate of high-risk HPV among all groups(P<0.05).2.Comparison of folic acid levels:(1)The serum and dietary folic acid contents of the study group were lower than those of the control group(P<0.05);(2)There was a positive correlation between serum folic acid and dietary folic acid content(r = 0.301,P<0.05).(3)The risk of HPV infection increased with dietary folic acid deficiency(P<0.05).3.Comparison of folate metabolism genes:(1)The frequency of TT type and T allele of MTHFR C677 T in study group was higher than that in control group(P<0.05);(2)There was no significant difference in allele frequency of MTHFR A1298 C among the three groups(P>0.05).(3)The frequency of AG type and G allele of MTRR A66 G in study group was higher than that in control group 1(P<0.05),and the frequency of G allele of MTRR A66 G in control group 2 was higher than that in control group 1(P<0.05).(4)The C/T allele,MTRR genotype and allele of MTHFR were significantly different in the presence or absence of HPV infection(P<0.05).4.Analysis of folic acid content and gene polymorphism of folic acid metabolism:(1)The serum folate content of TT type in MTHFR C677 T was lower than that of CC type and CT type(P<0.05);(2)The serum folic acid content of MTRR A66 G was higher than that of AG and GG(P<0.05).(3)There was no significant difference between MTHFR A1298 C genotypes and serum folic acid content(P>0.05).(4)There was no significant difference between folic acid gene polymorphism and dietary folic acid content(P>0.05).5.Correlation analysis of folic acid content and folic acid metabolism gene polymorphism with pathological characteristics of cervical squamous cell carcinoma:(1)the incidence of pelvic lymph node metastasis in folate deficiency group was higher than that in normal folate group,and there was correlation(r=-0.408,P<0.05);(2)The incidence of low differentiation of cervical squamous cell carcinoma in folate deficiency group was higher than that in normal folate group,and there was a correlation(r =-0.411,P<0.05).(3)MTRR A66 G gene polymorphism was correlated with histological differentiation(r =-0.474,P<0.05).Conclusion: 1.Inadequate serum and dietary folic acid levels may increase the risk of cervical squamous cell carcinoma and its precancerous lesions,and serum folic acid is related to dietary folic acid,and dietary folic acid deficiency may further increase HPV infection rates.2.Insufficient serum folic acid content may promote the occurrence of pelvic lymph node metastasis and low differentiation of cervical squamous cell carcinoma.3.The C/T allele of MTHFR,MTRR genotype and allele polymorphism affect HPV infection rate;MTHFR C677 T and MTRR A66 G gene polymorphisms may increase the risk of cervical squamous cell carcinoma,and MTRR A66 G gene polymorphisms may promote the occurrence of low differentiation of cervical squamous cell carcinoma.