br Fig Genotype distribution and allele
Fig. 6. Genotype distribution and allele frequency of rs9282861 of SULT1A1 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 rs9282861 it was in close agreement with Africans and Hispanics.
distributed similarly between the cases and the controls. The enzyme CYP1B1 catalyzes the formation 4-hydroxylated estradiol, which is genotoxic; it also activates procarcinogen from the environment, namely, heterocyclic aromatic amines and polycyclic aromatic hydro-carbons (Carnell et al., 2004; John et al., 2009; McFadyen et al., 2004; Ragavan et al., 2004). The production of 4-hydroxy estradiol is asso-ciated with hormone-related tumors (Singh et al., 2008a, 2008b). The gene CYP1B1 encodes the enzyme that takes part in estradiol conver-sion to highly reactive compound catechol estrogen, which is thought to be a mammary carcinogen (Liehr et al., 1986). The variant allele of CYP1B1 L432V possess higher catalytic activity in comparison with the wild-type allele (Hanna et al., 2000; Li et al., 2000). In a study con-ducted in Portland, the heterozygous variant allele of CYP1B1 L432V showed higher serum concentrations of estradiol than the wild-type homozygous one (García-Closas et al., 2002). Another study also de-monstrated the same results in postmenopausal women (De, 2002). Studies were also conducted on determining the contribution of CYP1B1 polymorphism to breast cancer risk across the globe, for ex-ample, in Korean and Turkish populations, as a pharmacogenetic study, and as a meta-analysis in Chinese population (Hanna et al., 2000;
Kocabaş et al., 2002; Lee et al., 2003; Wen et al., 2005). Association studies were also carried out on the functional polymorphism and cir-culating levels of sex steroid hormones (Dunning et al., 2004). The study revealed no association of the CYP1B1 polymorphism with breast carcinoma. The result obtained is contradictory to the findings in Caucasian, Swedish, Turkish, Han Chinese, and Egyptian populations (Cerne et al., 2011; Dunning et al., 2004; Jiang et al., 2010; Kocabaş et al., 2002; Rylander-Rudqvist et al., 2003; Tolba et al., 2017; Wang et al., 2007). In a study conducted on Ningxia Han population, no as-sociation with ER and PR status was observed (Liu et al., 2009). Some studies have reported the association with CC allele in Han Chinese population and also in Greenlandic Inuit women (Ghisari et al., 2014; Jiao et al., 2010). The variant of CYP1B1 was found to be associated with breast cancer risk in Mexican women (García-Martínez et al., 2017). A study conducted in Iraq showed significant association of both C and G PR619 of CYP1A1 m1 and m2 with breast cancer (Naif et al., 2018). G allele showed susceptibility in Brazilian and Egyptian popu-lations (Oliveira et al., 2015; Tolba et al., 2017). r> The transition of G to A at the nucleotide position 638 at codon 213 in exon 7 of SULT1A1 leads to the substitution of histidine amino acid for arginine, causing a reduction in the sulfotransferase enzyme ac-tivity. The steroid hormone estradiol is the ligand for binding to the estrogen receptor. The hormone estradiol is inactivated by the enzymes sulfotransferases. The estradiol on sulfation becomes inactive and ex-hibits poor binding ability to the estrogen receptors (Nowell et al., 2005). This attractive platform has paved the way for many studies on determining the related association of genetic variants of SULT1A1 gene and breast cancer risk. The human cytosolic SULT1A1 gene was examined in many studies owing to its potential role in the metabolic pathway of steroid hormones and carcinogens. The occurrence of functional polymorphism in SULT1A1 gene leads to low activity of enzymes and low thermal stability. As the gene SULT1A1 sulfates the hormone estrogen and exhibits antiestrogenic activity, the gene is in-vestigated in terms of its role in pharmacogenomics of response to the tamoxifen treatment (Daniels and Kadlubar, 2013). Studies conducted on breast cancer cells have shown that cells positive for estrogen re-ceptor had less estrogen sulfotransferase (Harris et al., 2000). Studies have showed varied results because of ethnic difference and sample size, with some studies demonstrating association whereas others showing no relationship between the genetic variants of the SULT1A1 gene and breast cancer risk.
SULT1A1 Arg213His was found to contribute to elevated risk of breast cancer. The results obtained on the genotyping analysis for rs9282861 were also similar in effect, as determined by stability pre-diction and pathogenicity analysis with computational tools revealing the SNP rs9282861 as interfering with the function and structure of the protein (Tables 1 and 6). SULT1A1 serves as a potential marker because SULT1A1 polymorphism influences the rate of drug clearance and is thereby related to drug toxicity. SULT1A1 polymorphism determines the benefit of tamoxifen therapy in patients. Determination of SULT1A1 genetic variation may help to predict the treatment outcome as to whether there will be a response or no response to hormonal therapy, drug toxicity, and in terms of recommendation for optimal dosing (Nowell et al., 2005; Wegman et al., 2007). The study carried out in Caucasians and Taiwanese did not show any association of SULT1A1 and breast carcinoma risk (Cheng et al., 2005; Langsenlehner et al., 2004). Studies conducted on Caucasian, African American, South In-dian, and Russian populations, studies conducted by Dumas and Diorio, and the meta-analysis study conducted by Wang et al. found no sig-nificant association between the breast carcinoma risk and the genetic variants of SULTIA1 gene (Dumas and Diorio, 2011; Gulyaeva et al., 2008; Reding et al., 2010; Syamala et al., 2010; Wang et al., 2007). The study carried by Seth et al. showed a relation with early-onset breast cancer (Seth et al., 2000). The study conducted by Zhen et al. revealed an association between the GA carriers in postmenopausal women (Zheng et al., 2001). Increased risk was conferred by SULT1A1