Analyses On The Relation Between MTHFR Polymorphism And Breast Cancer Susceptibility Of The Yunnan Population

Objective : This case-control study will investigate the association between MTHFR polymorphism and BRC clinical risk of the Yunnan population,it will discuss the relation between the polymorphism of MTHFR with the susceptibility, heredity and invasiveness of BRC,in order to find potential scientific evidences for the early prevention, diagnosis and guide individualized treatment of BRC.Methods: (1).This case-control study included 490 BRCs and relevant cancer-free controls.All subjects were from southwestern Chinese individuals.Patients were recruited from January 2012 to November 2015 at the Thirdly Affiliated Hospital of Kunming Medical University .Been diagnose with histologically confirmed BRC. At recruitment,demorgraphic information and clinical characteristics of each participant were collected.(2).Taking 1ml fasting whole blood and extract DNA with whole blood DNA extraction kit produced by Ameican company Promege.Useing NanoDrop 2000c measure concentration(C) and quality of DNA,to ensure C>40ng/ul.(3).Genotyping of MTHFR polymorphism was performed using matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry(MALDL-TOF MS), and to research whether gene polymorphism is in correlation with the susceptibility,development and prognosis of BRC(N=490) and control(N=490).(4).The genotype of MTHFR gene loci,tumor size,estrogen receptor(ER),progesterone receptor(PR),human epipdermal growth factor receptor 2(HER-2) in the frequency distributions were compared.(5). To compare demographic characteristics, the BRC each subtype of clinical characteristics and laboratory indexes and differences in allele frequency distribution of breast cancer group with control, calculated the OR and 95% CI, and compared different genotypes with relative risk of BRC development and prognosis .Results: (1).This case-control study included 490 BRCs and relevant cancer-free controls. The result shows that, there is no significant difference (P>0.05) in the average age of the breast cancer patients (48.01±9.86), and that of the normal control group (49.92±16.11). (2). In this case-control study,we detected all gene locus of MTHFR, including MTHFR5'-3'UTR,promoter and couding region. Detected genotype of 18 gene locus of MTHFR. The genotype frequency of MTHFR alleles in the case and control was in concordance with Hard-Weinerg equilibrium(HWE)(PHWE >0.005 )from Table2.1 .Two groups of samples have group representative(3).There is statistically significant difference (P =0.013) compared BRC in rs56221660(-1662A>G ) G and A allele frequencies with control. (4). There is statistically significant difference (P =0.01) compared BRC in rs1801133 (677G>A) (P=0.01 <0.05)? rs56221660(-1662A>G)(P=0.01 <0.05 ) genotype frequencies with control.(5). MTHFR rs1801133 (677G>A) polymorphism were detected three genotypes:GG,GA and AA. rs56221660 ( -1662A>G ) polymorphism were detected three genotypes:GG,GA and AA. rs1801131 ( 1298T>G) polymorphism were detected three genotypes: GG,GT and TT. (6). We found that breast cancer patients with GG and AA genotype of rs1801133 ( 677G>A ) had high risk of haven hypertension(OR=2.431, 95%CI: 1.286-4.598, P=0.008<0.05) and diabetes (OR=2.534,95%CI: 1.34-4.79,P=0.006<0.05),also in Luminal-B subtype, GG and AA genotype of rs1801133 ( 677G>A ) were more frequent in patients with high blood pressue(OR=3.721, 95%CI: 1.627-8.512, P=0.004<0.05) .(7). In Luminal-B subtype,rs 1801133 (677G>A) polymorphism were more frequent inpatients whose are over 48 years old (OR=1.871, 95%CI: 1.03-3.401, P=0.047<0.05),the polymorphism of rs1801133 (677G>A) is Luminal-B subtype breast cancer risk factors, especially in younger women.but on correlations with age of menophania and menopause.(8). In TNBC,GG and GT genotype were more frequent in patients who have breast cancer history (OR=6.429, 95%CI: 1.115-37.074, P=0.035<0.05).(9). The Luminal-A subtype patients whit rs1801131 ( 1298T>G ) G allele had very high risk of early progression ( OR=2.822 , 95%CI : 1.056-7.538 , P=0.041 < 0.05 ) .However,no correlation is found between rs1801131 ( 1298T>G) gene polymorphism and distant tumor metastasis or recurrence.(10) In BRC patients , rs56221660 (-1662A>G ) G allele was significantly associated with right breast tumors (OR=1.637, 95%CI :1.003-2.671, P=0.047<0.05) .(11) In HER-2 subtype, rs56221660 (-1662A>G )G allele was significantly associated with BMI>25 kg/m2 ( OR=1.231, 95%CI :0.973-1.557, P=0.032<0.05 ) (12) Analying all laboratory indexes, in TNBC,we found correlation between rs56221660 ( -1662A>G ) gene polymorphism and the concentration of ALT(OR=7.875, 95%CI: 1.129-54.931,P=0.049<0.05) and AST(OR=5.814, 95%CI: 1.791-18.87, P=0.003<0.05).Conclusions: In this case-control study,we found that MTHFR rs1801133(677G>A) and rs56221660 (-1662A>G) gene polymorphisms are associated with breast cancer(BRC) susceptibility. Rs 1801133 (677G>A) GG and AA genotype was the BRC patients complicated with hypertension and diabetes risk factors.As well as,the rs1801133 (677G>A) gene polymorphism increase the women whose are over 48 years old with Luminal-B subtype of breast cancer risk.For women who has family history of breast cancer,the rs 1801131 (1298T>G) GG and GT genotype had very high risk of hanving TNBC. At same time,we found that the Luminal-A subtype patients whit rs1801131 ( 1298T>G ) G allele had very high risk of early progression,but no correlation is found between rs1801131 ( 1298T>G ) gene polymorphism and distant tumor metastasis or recurrence.Rs56221660 (-1662A>G)gene loci polymorphism was associated with the primary site of tumor,and evaluated the lipid metabolism and nutritional status of BRC patients.