葡萄糖醛酸转移酶和膜转运体的常见变体作为结直肠癌潜在风险因素的病例对照研究。
Common variants in glucuronidation enzymes and membrane transporters as potential risk factors for colorectal cancer: a case control study.
机构信息
Oncology Department, CHU Limoges, Limoges, France.
UMR-1248, Inserm, CHU Limoges, Univ. Limoges, Limoges, France.
出版信息
BMC Cancer. 2017 Dec 28;17(1):901. doi: 10.1186/s12885-017-3728-0.
BACKGROUND
Associations between polymorphisms of UDP-glucuronosyltransferases (UGTs) or efflux transporters (e.g., P-glycoprotein and MRP2) and different types of cancer have been described, whereas the role of influx transporters (e.g. OATP1B1 and OATP2B1) has been seldom explored. The GenColon study investigated potential associations between variant alleles of UGTs, efflux and influx transporters and CRC.
METHODS
Three hundred CRC cases were matched with 300 controls for age, sex and enrolment site. Fifteen SNPs in UGT1A6-9, UGT2B7, ABCB1, ABCC2, SLCO1B1 and SLCO2B1 genes were characterized using Taqman® PCR. Using multivariate conditional logistic regression, we investigated the relationships between CRC and "environmental" risk factors (physical activity, housing and working areas, consumption of red meat, tobacco, alcohol); genetic polymorphisms, in the study population and in the subgroups with "environmental" risk factors.
RESULTS
No significant association was observed for the analyzed SNPs (or haplotypes). However, an increased CRC risk was found in carriers of the UGT1A8 rs1042597-G variant allele (additive risk OR = 3.39[1.29-8.89], p = 0.02951) in the subgroup of meat-consumers (n = 84), and in carriers of the ABCB1 rs1045642-T (exon26) variant allele (additive risk; OR = 1.89[1.10-3.39], p = 0.0257) in the "never alcohol consumption subgroup" (n = 125). In addition, as previously reported, the following CRC risk factors were identified: absence of physical activity (OR = 6.35[3.70-10.9], p < 0.0001), living or working in rural or mix area (OR = 2.50[1.48-4.23], p = 0.0006 and OR = 2.99[1.63-5.48], p = 0.004, respectively) and tobacco exposure >30 years (3.37[1.63-6.96], p = 0.0010).
CONCLUSIONS
Variant genotypes of influx transporters (OATP1B1 and 2B1) were not associated with CRC. This study confirmed the influence of lifestyle factors, but not the previously reported detrimental effect of SNPs in intestinal UGTs or efflux transporters, except for a UGT1A8 variant in subjects consuming meat and the exon 26 SNP of ABCB1 in the never alcohol consumption subgroup.
TRIAL REGISTRATION
Registered in Direction Générale de la Santé the 1st July 2008 under the number DGS2008-0144.
背景
已描述 UDP-葡萄糖醛酸基转移酶（UGTs）或外排转运体（如 P-糖蛋白和 MRP2）的多态性与不同类型癌症之间的关联，而流入转运体（如 OATP1B1 和 OATP2B1）的作用很少被探索。GenColon 研究调查了 UGT、外排和流入转运体的变体等位基因与 CRC 之间的潜在关联。
方法
将 300 例 CRC 病例与 300 例对照匹配，以年龄、性别和入组地点为匹配条件。使用 Taqman®PCR 对 UGT1A6-9、UGT2B7、ABCB1、ABCC2、SLCO1B1 和 SLCO2B1 基因中的 15 个 SNP 进行了特征描述。使用多变量条件逻辑回归，我们研究了 CRC 与“环境”风险因素（体力活动、住房和工作区域、红肉、烟草、酒精消费）之间的关系；在研究人群中以及在具有“环境”风险因素的亚组中，研究了遗传多态性。
结果
未观察到分析的 SNP（或单倍型）之间存在显著关联。然而，在食用肉类亚组（n=84）中，UGT1A8 rs1042597-G 变体等位基因携带者（加性风险 OR=3.39[1.29-8.89]，p=0.02951）和从不饮酒亚组（n=125）中，ABCB1 rs1045642-T（外显子 26）变体等位基因携带者（加性风险；OR=1.89[1.10-3.39]，p=0.0257）中发现 CRC 风险增加。此外，如先前报道的，确定了以下 CRC 风险因素：缺乏体力活动（OR=6.35[3.70-10.9]，p<0.0001）、居住或工作在农村或混合地区（OR=2.50[1.48-4.23]，p=0.0006 和 OR=2.99[1.63-5.48]，p=0.004）和烟草暴露>30 年（3.37[1.63-6.96]，p=0.0010）。
结论
流入转运体（OATP1B1 和 2B1）的变体基因型与 CRC 无关。本研究证实了生活方式因素的影响，但未证实先前报道的肠道 UGT 或外排转运体 SNP 的有害影响，除了在食用肉类的受试者中 UGT1A8 变体和从不饮酒亚组中的 ABCB1 外显子 26 SNP 外。
试验注册
于 2008 年 7 月 1 日在法国卫生部注册，编号为 DGS2008-0144。
Zotero 插件