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波兰患者中CYP1A1基因Ile462Val多态性与结直肠癌风险

CYP1A1 Ile462Val polymorphism and colorectal cancer risk in Polish patients.

作者信息

Gil Justyna, Gaj Paweł, Misiak Błażej, Ostrowski Jerzy, Karpinski Pawel, Jarczyńska Alicja, Kielan Wojciech, Sasiadek Maria Malgorzata

机构信息

Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1, 50-368, Wroclaw, Poland,

出版信息

Med Oncol. 2014 Jul;31(7):72. doi: 10.1007/s12032-014-0072-y. Epub 2014 Jun 18.

Abstract

Colorectal cancer (CRC) is an epidemiological problem of a great importance in Poland; each year approximately 14,600 new cases of the disease are diagnosed. Mortality associated with CRC reaches approximately 10,400 cases per year (according to the National Cancer Registry). The 5-year survival rate is approximately 25 %, which is one of the lowest rates in Europe. The etiology of sporadic colorectal cancer (CRC) is multifactorial and has been attributed to an interplay between both environmental and genetic risk factors. In addition, there is a general consensus that genetic factors may modulate the influence of environmental insults. Following these assumptions, we performed a study on widely described polymorphisms in xenobiotic-metabolizing enzymes and DNA repair genes which may influence individual susceptibility to cancer. We selected five candidate polymorphisms in following genes: ERCC1 Asp118Asn (rs11615), XPC i11C/A (rs2279017), XRCC3 Met241Thr (rs861539) CYP1A1 Ile462Val (rs1048943) and NAT2 A803G (rs1208) and assessed the importance of chosen SNPs on groups consisting of 478 CRC patients and 404 controls. Only CYP1A1 Ile462Val was statistically significant in CRC patients over 50 years old: OR 2.05 (1.29-3.28); p = 1.25E-02 and this association was more pronounced in the female group of CRC patients after the age of 50: OR 2.72 (1.43-5.14); p = 1.14E-02.

摘要

在波兰,结直肠癌(CRC)是一个极为重要的流行病学问题;每年约有14,600例新发病例被诊断出来。与结直肠癌相关的死亡率每年约达10,400例(根据国家癌症登记处的数据)。5年生存率约为25%,这是欧洲最低的生存率之一。散发性结直肠癌(CRC)的病因是多因素的,归因于环境和遗传风险因素之间的相互作用。此外,人们普遍认为遗传因素可能调节环境损伤的影响。基于这些假设,我们对广泛描述的外源性代谢酶和DNA修复基因中的多态性进行了研究,这些多态性可能影响个体对癌症的易感性。我们在以下基因中选择了五个候选多态性:ERCC1 Asp118Asn(rs11615)、XPC i11C/A(rs2279017)、XRCC3 Met241Thr(rs861539)、CYP1A1 Ile462Val(rs1048943)和NAT2 A803G(rs1208),并评估了所选单核苷酸多态性(SNP)对由478例CRC患者和404例对照组成的群体的重要性。只有CYP1A1 Ile462Val在50岁以上的CRC患者中具有统计学意义:比值比(OR)为2.05(1.29 - 3.28);p = 1.25×10⁻²,并且这种关联在50岁以上的女性CRC患者组中更为明显:OR为2.72(1.43 - 5.14);p = 1.14×10⁻²。

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