Al-Mukaynizi Fatimah Basil, Alanazi Mohammed, Al-Daihan Sooad, Parine Narasimha Reddy, Almadi Majid, Aljebreen Abdulrahman, Azzam Nahla, Alharbi Othman, Arafah Maha, Warsy Arjumand
Department of Biochemistry, College of Science.
Department of Internal Medicine.
Onco Targets Ther. 2017 Sep 14;10:4559-4567. doi: 10.2147/OTT.S121557. eCollection 2017.
Considerable interest is directed toward the enzyme aromatase (CYP19A1) and the development of cancer, due to CYP19A1's role in estrogen biosynthesis. Several cancers display excessive intra-tumor accumulation of estrogens, and aromatase inhibitors are used for treatment. The CYP19A1 gene exhibits polymorphism and mutations that can alter its expression or aromatase activity and influence estrogen production. We designed this study to investigate the link between CYP19A1 polymorphism and susceptibility to colorectal cancer (CRC) development in Saudis.
Blood samples from 100 CRC patients and 100 healthy controls were drawn for DNA extractions. Three polymorphic sites, rs4774585, rs936308, and rs4775936, were genotyped using Taqman genotyping by real-time polymerase chain reaction. Allelic and genotype frequencies were calculated and compared in the two groups.
All single nucleotide polymorphisms (SNPs) were polymorphic in Saudis, and comparison of allele frequencies showed several differences when compared to other populations. None of the SNPs were associated with the risk of CRC development in Saudis (>0.05). Some gender and location (colon or rectal) differences were observed.
The results of this study highlighted the genetic heterogeneity existing between populations in the prevalence of different SNPs and their relation to disease state. It showed that, although rs4774585, rs936308, and rs4775936 are involved in CRC development in several populations, their role is not significant in the etiology of CRC in Saudis; however, some SNPs do increase susceptibility or resistance to CRC development as judged from the odds ratio. Further large-scale studies are warranted to clarify the role of the CYP19A1 development in CRC.
由于细胞色素P450芳香化酶（CYP19A1）在雌激素生物合成中的作用，人们对该酶与癌症发展产生了浓厚兴趣。几种癌症表现出肿瘤内雌激素过度蓄积，芳香化酶抑制剂可用于治疗。CYP19A1基因存在多态性和突变，可改变其表达或芳香化酶活性，并影响雌激素生成。我们开展本研究以调查沙特人群中CYP19A1基因多态性与结直肠癌（CRC）发生易感性之间的联系。
采集100例CRC患者和100例健康对照者的血样用于DNA提取。使用实时聚合酶链反应的Taqman基因分型法对3个多态性位点rs4774585、rs936308和rs4775936进行基因分型。计算并比较两组的等位基因频率和基因型频率。
所有单核苷酸多态性（SNP）在沙特人群中均具有多态性，与其他人群相比，等位基因频率比较显示出若干差异。在沙特人群中，没有一个SNP与CRC发生风险相关（>0.05）。观察到一些性别和部位（结肠或直肠）差异。
本研究结果突出了不同人群在不同SNP患病率及其与疾病状态关系方面存在的遗传异质性。结果表明，尽管rs4774585、rs936308和rs4775936在一些人群的CRC发生中起作用，但它们在沙特人群CRC病因学中的作用并不显著；然而，从优势比判断，一些SNP确实会增加CRC发生的易感性或抗性。有必要开展进一步的大规模研究以阐明CYP19A1在CRC发生中的作用。
