Study On The Correlation Between CHEK2 Gene Polymorphism And Sporadic Breast Cancer In Inner Mongolia

Objective:Cell cycle regulated kinase gene 2(CHEK2)is a multifunctional serine/threonine kinase protein that plays an important role in the repair process of DNA double strand damage.It has been confirmed that CHEK2 is a tumor suppressor gene,and its mutation plays an important role in gastric cancer,prostate cancer,ovarian cancer and other cancers.Of course,it is also closely related to the occurrence and development of breast cancer.Currently,some foreign studies have confirmed that there are certain differences in the expression of CHEK2 gene mutations in different regions and different ethnic groups,but comparative studies on CHEK2 gene mutations between two ethnic groups in the same region are relatively rare in China.This study examined the single nucleotide polymorphisms of the CHEK2 gene rs121908700 and rs137853011,in order to explore its distribution and clinical significance in sporadic breast cancer among Mongolian and Han nationalities in Inner Mongolia.Methods:From February 2022 to October 2022,124 patients with complete clinical data and confirmed by pathological data were collected from the Nail and Breast Surgery Department of the Affiliated Hospital of Inner Mongolia Medical University.Among them,62 patients with primary breast cancer were in the case group(20 patients of Mongolian nationality,42 patients of Han nationality),and 62 patients with benign breast disease were in the control group(20 patients of Mongolian nationality,42 patients of Han nationality).All patients were informed and agreed to the study,and sign an informed consent form.All patients were treated with EDTA anticoagulation and vacuum blood sampling,and 2 ml of peripheral venous blood was taken as a sample for DNA extraction under a state of fasting for more than12 hours.Then,polymerase chain reaction(PCR)and direct sequencing were used to detect the single nucleotide polymorphisms at the two loci of the CHEK2 gene,rs121908700 and rs137853011.The experimental data and clinical data were statistically analyzed using SPSS26.0 statistical software.A Hardy Weinberg equilibrium test was conducted on the distribution frequencies of each genotype at the two loci rs121908700 and rs137853011,and P>0.05 was considered to be consistent with the Hardy Weinberg equilibrium rule.Measurement data adopts mean ± standard deviation( ±s)means that the mean between groups was compared using a t-test.Counting data were expressed in terms of number of cases and percentage(%).Chi-square test and Fisher exact probability method were used for comparison between groups.Mutations at the two loci rs121908700 and rs137853011 of the gene CHEK2 were used as independent variables,and the presence or absence of a case group was used as a variable factor(No=0,Yes=1).The relationship between genotypes and alleles of CHEK2 and the risk of breast cancer was evaluated by binary logistic regression analysis.Inspection level α= 0.05.Results:(1)Two genotypes(AA,AC)and two alleles(A,C)of rs121908700 locus could be detected in female patients with primary breast cancer and female patients with benign breast lesions between Mongolian and Han nationalities in Inner Mongolia.According to Hardy Weinberg Equilibrium test,P>0.05 indicates that they all comply with the Haven equilibrium rule.However,no statistical difference was found in the secondary grouping of Mongolian and Han nationalities,that is,P>0.05.(2)There was no statistical difference in the distribution of the single nucleotide polymorphism of rs121908700 locus in various clinical general conditions of primary breast cancer,such as the onset age,primary tumor diameter,immunohistochemical(ER,PR,Her-2and Ki-67 expression),histological grading,and lymph node metastasis,P>0.05.(3)In the primary breast cancer group and the benign breast disease group,with AA type as the reference,there was no statistical difference in the distribution of mutant AC type(OR=1.321,95% CI=0.426?3.013,P>0.05).Allele C also showed no statistical difference(OR=1.121,95% CI=0.439?2.861,P>0.05).(4)Two genotypes(GG,GA)and two alleles(G,A)of the CHEK2 gene rs137853011 locus can be detected in women with primary breast cancer and women with benign breast lesions between Mongolian and Han nationalities in Inner Mongolia.According to Hardy Weinberg Equilibrium test,P>0.05 indicates that they all comply with the Haven equilibrium rule.However,no statistical difference was found in the secondary grouping of Mongolian and Han nationalities,that is,P>0.05.(5)The single nucleotide polymorphism of rs137853011 site was statistically different in the PR expression and histological grading of primary breast cancer,with P values less than0.05,but it was not statistically significant in the distribution of age at onset,diameter of primary tumor,immunohistochemistry(expression of ER,Her-2 and Ki-67),lymph node metastasis and other clinical general conditions,P>0.05.(6)In the primary breast cancer group and the benign breast disease group,when GG type was used as a reference,there was no statistical difference in the distribution of mutant GA type(OR=0.872,95% CI=0.313 to 2.432,P>0.05).Allele A also showed no statistical difference(OR=0.881,95% CI=0.329?2.364,P>0.05).Conclusion:(1)The single nucleotide polymorphisms at rs121908700 and rs137853011 of CHEK2 gene may not be associated with the risk of sporadic breast cancer in Inner Mongolia.(2)The single nucleotide polymorphisms and allele distribution frequencies of the rs121908700 and rs137853011 genes at the two sites of CHEK2 were not significantly different between Mongolian and Han nationalities in Inner Mongolia.(3)The single nucleotide polymorphism of the CHEK2 gene locus rs137853011 may be associated with the PR expression and histological grading of patients with primary breast cancer in Inner Mongolia,that is,the polymorphism of this gene locus may affect the prognosis of breast cancer.