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N-乙酰基转移酶 2 基因多态性与结直肠癌风险。

N-Acetyltransferase 2 genetic polymorphisms and risk of colorectal cancer.

机构信息

Oncology Group - Gastroenterology Division, Universidade Federal de São Paulo, 04023-900 São Paulo, Brazil.

出版信息

World J Gastroenterol. 2011 Feb 14;17(6):760-5. doi: 10.3748/wjg.v17.i6.760.

DOI:10.3748/wjg.v17.i6.760
PMID:21390146
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3042654/
Abstract

AIM

To investigate the possible association between meat intake, cigarette smoking and N-acetyltransferase 2 (NAT2) genetic polymorphisms on colorectal cancer (CRC) risk.

METHODS

Patients with CRC were matched for gender and age to healthy controls. Meat intake and cigarette smoking were assessed using a specific frequency questionnaire. DNA was extracted from peripheral blood and the genotypes of the polymorphism were assessed by polymerase chain reaction-restriction fragment length polymorphism. Five NAT2 alleles were studied (WT, M1, M2, M3 and M4) using specific digestion enzymes.

RESULTS

A total of 147 patients with colorectal cancer (76 women and 90 men with colon cancer) and 212 controls were studied. The mean age of the two groups was 62 years. More than half the subjects (59.8% in the case group and 51.9% in the control group) were NAT2 slow acetylators. The odds ratio for colorectal cancer was 1.38 (95% CI: 0.90-2.12) in slow acetylators. Although the number of women was small (n = 76 in the case group), the cancer risk was found to be lower in intermediate (W/Mx) acetylators [odds ratio (OR): 0.55, 95% confidence interval (95% CI): 0.29-1.02]. This difference was not observed in men (OR: 0.56, 95% CI: 0.16-2.00). Among NAT2 fast acetylators (W/W or W/Mx), meat consumption more than 3 times a week increased the risk of colorectal cancer (OR: 2.05, 95% CI: 1.01-4.16). In contrast, cigarette smoking increased the risk of CRC among slow acetylators (OR: 1.97, 95% CI: 1.02-3.79).

CONCLUSION

The risk of CRC was higher among fast acetylators who reported a higher meat intake. Slow NAT2 acetylation was associated with an increased risk of CRC.

摘要

目的

研究肉类摄入量、吸烟与 N-乙酰基转移酶 2(NAT2)基因多态性与结直肠癌(CRC)风险之间的可能关联。

方法

按性别和年龄与健康对照相匹配,对 CRC 患者进行肉类摄入量和吸烟情况的评估,采用特定频率问卷。从外周血中提取 DNA,并采用聚合酶链反应-限制性片段长度多态性评估多态性的基因型。使用特定的消化酶研究了 5 种 NAT2 等位基因(WT、M1、M2、M3 和 M4)。

结果

共研究了 147 例结直肠癌患者(76 例女性和 90 例男性结肠癌)和 212 例对照。两组的平均年龄为 62 岁。超过一半的受试者(病例组 59.8%,对照组 51.9%)为 NAT2 慢乙酰化酶。在慢乙酰化酶中,结直肠癌的比值比为 1.38(95%CI:0.90-2.12)。尽管女性人数较少(病例组 76 人),但中间乙酰化酶(W/Mx)的癌症风险较低[比值比(OR):0.55,95%置信区间(95%CI):0.29-1.02]。这一差异在男性中未观察到(OR:0.56,95%CI:0.16-2.00)。在 NAT2 快乙酰化酶(W/W 或 W/Mx)中,每周食用肉类超过 3 次会增加结直肠癌的风险(OR:2.05,95%CI:1.01-4.16)。相比之下,吸烟会增加慢乙酰化酶 CRC 的风险(OR:1.97,95%CI:1.02-3.79)。

结论

每周食用肉类较多的快乙酰化酶患者结直肠癌风险更高。NAT2 慢乙酰化与 CRC 风险增加有关。

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