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N-乙酰转移酶2/环境因素及其作为散发性结肠癌和直肠癌调节性危险因素的关联

N-acetyl transferase 2/environmental factors and their association as a modulating risk factor for sporadic colon and rectal cancer.

作者信息

Procopciuc Lucia M, Osian Gelu, Iancu Mihaela

机构信息

Department of Medical Biochemistry, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.

Multi Organ Transplant Center, King Fahad Specialist Hospital, Dammam, Saudi Arabia.

出版信息

J Clin Lab Anal. 2017 Sep;31(5). doi: 10.1002/jcla.22098. Epub 2016 Nov 24.

DOI:10.1002/jcla.22098
PMID:27883249
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6816822/
Abstract

OBJECTIVES

The aim of this study was to evaluate the association between environmental factors and colon or rectal cancer after adjusting for N-acetyl transferase 2 (NAT2) phenotypes.

METHODS

Ninety-six patients with sporadic colon cancer, 54 with sporadic rectal cancer and 162 control subjects were genotyped for NAT2-T341C, G590A, G857A, A845C, and C481T using sequencing and PCR-RFLP analysis.

RESULTS

The risk for colon cancer was increased in carriers of the homozygous negative genotypes for NAT25C-T341C, NAT26B-G590A, NAT27B-G857A, NAT218-A845C, and NAT25A-C481T. The risk for rectal cancer was increased in carriers of the homozygous negative genotypes for NAT25C-T341C, NAT27B-G857A, and NAT25A-C481T. High fried red meat intake associated with NAT2-T341C, G590A, G857A, A845C, and C481T rapid acetylator allele determines a risk of 2.39 (P=.002), 2.39 (P=.002), 2.37 (P=.002), 2.28 (P=.004), and 2.51 (P=.001), respectively, for colon cancer, whereas in the case of rectal cancer, the risk increased to 7.55 (P<.001), 7.7 (P<.001), 7.83 (P<.001), 7.51 (P<.001), and 8.62 (P<.001), respectively. Alcohol consumption associated with the NAT2 -T341C, G590A, G857A, A845C, and C481T rapid acetylator allele induces a risk of 10.63 (P<.001), 12.04 (P<.001), 9.76 (P<.001), 10.25 (P<.001), and 9.54 (P<.001), respectively, for colon cancer, whereas the risk for rectal cancer is 9.72 (P<.001), 11.24 (P<.001), 13.07 (P<.001), 10.04 (P<.001), and 9.43 (P<.001), respectively. Smokers with NAT2-T341C, G590A, G857A, A845C, and C481T rapid acetylator allele have a risk of 4.87, 4.25, 4.18, 3.81, and 3.82, respectively, to develop colon cancer.

CONCLUSIONS

Fried red meat, alcohol, and smoking increase the risk of sporadic CRC, especially of colon cancer, in the case of rapid acetylators for the NAT2 variants.

摘要

目的

本研究旨在评估在调整N - 乙酰转移酶2(NAT2)表型后,环境因素与结肠癌或直肠癌之间的关联。

方法

采用测序和聚合酶链反应 - 限制性片段长度多态性分析(PCR - RFLP)对96例散发性结肠癌患者、54例散发性直肠癌患者和162例对照者进行NAT2 - T341C、G590A、G857A、A845C和C481T基因分型。

结果

NAT25C - T341C、NAT26B - G590A、NAT27B - G857A、NAT218 - A845C和NAT25A - C481T纯合阴性基因型携带者患结肠癌的风险增加。NAT25C - T341C、NAT27B - G857A和NAT25A - C481T纯合阴性基因型携带者患直肠癌的风险增加。与NAT2 - T341C、G590A、G857A、A845C和C481T快速乙酰化等位基因相关的高油炸红肉摄入量,分别使患结肠癌的风险增加至2.39(P = 0.002)、2.39(P = 0.002)、2.37(P = 0.002)、2.28(P = 0.004)和2.51(P = 0.001),而对于直肠癌,风险分别增加至7.55(P < 0.001)、7.7(P < 0.001)、7.83(P < 0.001)、7.51(P < 0.001)和8.62(P < 0.001)。与NAT2 - T341C、G590A、G857A、A845C和C481T快速乙酰化等位基因相关的酒精消费,分别使患结肠癌的风险增加至10.63(P < 0.001)、12.04(P < 0.001)、9.76(P < 0.001)、10.25(P < 0.001)和9.54(P < 0.001),而患直肠癌的风险分别为9.72(P < 0.001)、11.24(P < 0.001)、13.07(P < 0.001)、10.04(P < 0.001)和9.43(P < 0.001)。携带NAT2 - T341C、G590A、G857A、A845C和C481T快速乙酰化等位基因的吸烟者患结肠癌的风险分别为4.87、4.25、4.18、3.81和3.82。

结论

对于NAT2变体的快速乙酰化者,油炸红肉、酒精和吸烟会增加散发性结直肠癌尤其是结肠癌的风险。

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