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  • br Stratified analysis of the genotypes

    2020-08-24


    Stratified analysis of the genotypes of rs9282861 of SULT1A1 with clinical characteristic like receptor status showed significant association of AG geno-type OR:2.2 p: 0.008** with UNC-1999 positive breast cancer patients. p < 0.05. p < 0.01.
    Fig. 2. Crystal structure of SULT1A1 Arg213His
    Red color indicates variant and blue denotes the native structure.
    For rs4646903 the genotype was similar with Africans and Caucasians, for the other polymorphism rs1048943 and rs1056836 the genotype of controls was similar to South Asians, and for rs9282861 it was in close agreement with Caucasians and Hispanics (Fig. 3–6). The results obtained on the genotyping analysis for rs9282861 were also similar in effect as determined by stability prediction and patho-genicity analysis with computational tools, revealing that the SNP was interfering with function and structure of the SULT1A1 protein (Table 6, Fig. 2). Haplotypes were not informative (Fig. 1). CYP1A1, SULT1A1 was found to be associated with premenopausal breast cancer cases (Table 3). Stratified analysis of the subjects based on tumor grade revealed the association of CYP1A1, SULT1A1 polymorphisms to be
    associated with breast cancer risk (Table 4). Stratified analysis of the subjects based on receptor status revealed an association between SULT1A1 and ER-positive receptor (Table 5).
    4. Discussion
    The study revealed positive association of CYP1A1 rs4646903 T to C polymorphism with breast cancer risk. A significant increase of TC and
    The result obtained for the CYP1A1 genetic variant rs1048943 did not show an association of the polymorphism with breast cancer risk because a similar pattern of the genotype distribution between the breast cancer group and the controls were obtained. The result obtained showed discrepancy from the previous studies conducted in India, especially the one conducted by Chacko et al., 2005 and another study by Surekha et al., 2009, where an association of significance was found (Surekha et al., 2009). The CYP1A1*2 polymorphism results in elevated enzyme activity, resulting in the formation of highly reactive inter-mediates from carcinogen, drugs, and estrogen. Other studies con-ducted in USA, in Iranian Population, in Iraq population and Con-necticut (Ambrosone et al., 1995; Ishibe et al., 1998; Naif et al., 2018; Rahmati et al., 2016; Taioli et al., 1995; Zhang et al., 2004) also showed a significant association. The frequency of occurrence of Val allele was higher in the breast cancer group with regard to the stage of the cancer in the study from India (Surekha et al., 2009). The results of the study were in concordance to the studies conducted previously in African-American white women, two studies from the Chinese population, one study from Brazilian population, one study from the United Kingdom, and studies from the North Indian, South Indian, Jordan, Russian, and Korea (Amrani et al., 2016; Basham et al., 2001; Boyapati et al., 2005; de Amorim et al., 2002; Huang et al., 1999; Kiruthiga et al., 2011; Li et al., 2004; Petchkovskiy et al., 2014; Shin et al., 2007; Singh et al.,
    Fig. 3. Genotype distribution and allele frequency of rs4646903 of gene CYP1A1 in world ethnic groups from NCBI.
    Genotype distribution and allele frequency of the study was compared with the data of other ethnic groups from the NCBI database; for rs4646903 the genotype was similar with Africans and Caucasians.
    Fig. 4. Genotype distribution and allele frequency of rs1048943 of gene CYP1A1 in world ethnic groups from NCBI.
    Genotype distribution and allele frequency of the controls of the study was compared with the data of other ethnic groups from the NCBI database; the polymorphism rs1048943 was similar to South Asians and Caucasians.
    Fig. 5. Genotype distribution and allele frequency of rs1056836 of gene CYP1A1 in world ethnic groups from NCBI.
    Genotype distribution and allele frequency of the controls of the study was compared with the data of other ethnic groups from the NCBI database; for rs1056836 it was similar to South Asians.
    Table 6
    Prediction Tool Interpretation
    The stability and pathogenicity prediction analysis using the five tools (I-Mutant Suite, iStable, SNAP, PolyPhen2, and PROVEAN) revealed the variant rs9282861 of SULT1A1to be more ‘deleterious'and affecting the protein stability.
    2007). Polymorphisms in estrogen-metabolizing pathway also proved to have association with tobacco smoking (White et al., 2017). It was also proven that polymorphisms trigger aryl hydrocarbon hydroxylase and thereby cellular proliferation (Al-Dhfyan et al., 2017). For CYP1B1 rs1056836, the result obtained in the present study did not reveal an association with breast cancer risk, as the genotypes were