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  • br Prediction of deleterious variants br The

    2020-08-24

    
    2.3. Prediction of deleterious variants
    The protein sequence for SULT1A1 gene and its SNP (rs9282861) was obtained from SWISS-Protein database and from the National Centre for Biotechnology Information (NCBI) database, respectively. The 3D structure of SULT1A1 was obtained from PDB database. Five computational tools (I-Mutant Suite, iStable, PolyPhen2, SNAP, and PROVEAN) were used for in silico predictive analysis on the implication of the mutation on the function and structure of the variant SULT1A1 protein.
    2.4. Statistical analysis
    The SPSS statistical software ver. 19.0 was used for statistical ana-lysis. Chi-square goodness-of-fit test was carried out for comparison of expected and observed genotype frequencies for assessing Hardy Weinberg equilibrium. Chi-square test was done for comparing the frequencies of the genotype of the polymorphisms between the controls and subjects with breast cancer. Using the genotypes of the wild type as the reference group, the odds ratio (OR) and 95% confidence interval (CI) were determined. The level p < 0.05 was considered to be sig-nificant. For the SULT1A1 gene, computational tools are used to predict the protein stability of the variant SULT1A1 protein.
    Table 4
    Stratified analysis of the genotypes of the steroid metabolizing pathway with clinical characteristics like tumor grade.
    Genotype Low grade High grade OR 95% CI P value
    tumors % tumors %
    p value < 0.05 was considered to be statistically significant:
    3. Results
    3.1. Genotyping and breast cancer risk
    Breast cancer association with risk factors showed an association with oral contraceptive use (Table 1). Two polymorphisms rs4646903 and rs1048943 of CYP1A1, rs1056836 polymorphism of CYP1B1, and rs9282861 of SULT1A1 were studied with respect to breast cancer risk, as shown in Table 2. For CYP1A1 M1 rs4646903 T to C polymorphism, the frequency of homozygous wild-type TT was 55%, heterozygous mutant TC was 41%, and homozygous mutant CC was 4% in the control group. The frequency of homozygous wild-type TT was 42%, hetero-zygous mutant TC was 53%, and homozygous mutant CC was found to be 5% in the cases. A significant increase of TC and CC Suramin hexasodium salt of the gene CYP1A1 m1(T/C) genotype was found in patients in comparison with controls (OR = 1.66; 95% CI, 1.13–2.54; p: 0.01). For CYP1A1 M2 rs1048943 A to G polymorphism, the frequency of homozygous wild-type AA was 82%, heterozygous mutant AG was 17%, and homozygous mutant GG was 1% in the control group. The frequency of homozygous wild-type AA was 80%, heterozygous mutant AG was 18%, and homozygous mutant GG was 2% in the breast cancer patients. For CYP1B1 rs1056836 C to G polymorphism, the frequency of homozygous wild-type CC was 70%, heterozygous mutant CG was 28%, and homozygous mutant GG was 2% in the control group. The frequency of homozygous wild-type CC was 68%, heterozygous mutant AG was 29.5%, and homozygous mutant GG was 2.5% in the case group af-fected with breast cancer. In the present study, association of SULT1A1 rs9282861 G to A transition polymorphism with cases of breast cancer was studied. The frequency of homozygous wild-type GG was 76%, heterozygous mutant GA was 22.5%, and homozygous mutant AA was 1.50% in the control group. The frequency of homozygous wild-type GG was 63%, heterozygous mutant GA was 33.5%, and homozygous mu-tant AA was 3.50% in the breast cancer patients. Statistical difference in the genotype of CYP1A1 rs1048943 and CYP1B1 (rs1056836) poly-morphism was not found between patients' genotype and controls' genotype. Genotype distribution and allele frequency of the study was compared with the data of other ethnic groups from the NCBI database.  Meta Gene 19 (2019) 225–234
    Table 5
    Stratified analysis of the genotypes of the steroid metabolizing pathway with clinical characteristics like receptor status.
    Association between CYP1A1 rs4646903 and ER, PR and Her2 receptor status CYP1A1
    ER Positive ER Negative
    PR Positive PR Negative
    Her 2 Positive Her 2 Negative
    Association between CYP1A1 rs1048943 and ER, PR and Her2 Receptor Status CYP1A1
    ER Positive ER Negative
    PR Positive PR Negative
    Her 2 Positive Her 2 Negative
    Association between CYP1B1 rs1056836 and ER, PR and Her2 Receptor Status CYP1B1
    ER Positive ER Negative
    PR Positive PR Negative
    Her 2 Positive Her 2 Negative
    Association between SULT1A1 rs9282861 and ER, PR and Her2 Receptor Status SULT1A1
    ER Positive ER Negative
    PR Positive PR Negative
    Her 2 Positive Her 2 Negative
    (continued on next page)
    Table 5 (continued)
    Genotype Patient no (%)
    OR- odds ratio, CI-confidence interval, A, adenine; G, Guanine; T, Thymine; Odds ratio and 95% confidence interval were calculated. A p value < 0.05 was considered to be statistically significant.