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台湾队列中不同年龄组风险因素、分子特征与 CpG 岛甲基化表型结直肠癌的相关性。

Association between risk factors, molecular features and CpG island methylator phenotype colorectal cancer among different age groups in a Taiwanese cohort.

机构信息

Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.

Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.

出版信息

Br J Cancer. 2021 Jul;125(1):48-54. doi: 10.1038/s41416-021-01300-5. Epub 2021 Apr 12.

Abstract

BACKGROUND

CpG island methylator phenotype (CIMP) represents a carcinogenesis pathway of colorectal cancer (CRC) and the association between CIMP CRC, molecular features and risk factors in East Asian population is less studied.

METHODS

We prospectively enrolled newly diagnosed CRC patients at the National Taiwan University Hospital. Clinicopathological data and risk factors for CRC were collected during interview. The tumour samples were subjected to CIMP, RAS/BRAF mutation and microsatellite instability tests. CIMP-high was determined when ≧3 methylated loci of p16, MINT1, MINT2, MINT31 and MLH1 were identified. Multivariate logistic regression was used to evaluate the association between risk factors and CIMP-high CRC.

RESULTS

Compared with CIMP-low/negative CRC, CIMP-high CRC was associated with more stage IV disease, BRAF V600E mutation and high body mass index (BMI ≧ 27.5 kg/m) in younger patients (age < 50 y), and more right-sided tumour, BRAF V600E mutation, MSI-high and colorectal polyp in elder patients (age ≧ 50 y). Multivariate analyses showed that BMI ≧27.5 kg/m was significantly associated with CIMP-high CRC in younger patients.

CONCLUSIONS

We identified distinct clinicopathological features for CIMP-high CRC among different age groups in Taiwan. Our data suggest the association between BMI ≧27.5 kg/m and CIMP-high CRC in patients younger than 50 years.

摘要

背景

CpG 岛甲基化表型(CIMP)代表结直肠癌(CRC)的一种致癌途径,东亚人群中 CIMP-CRC、分子特征和危险因素之间的关联研究较少。

方法

我们前瞻性地招募了在国立台湾大学医院新诊断的 CRC 患者。在访谈中收集了临床病理数据和 CRC 的危险因素。对肿瘤样本进行 CIMP、RAS/BRAF 突变和微卫星不稳定性检测。当鉴定出 p16、MINT1、MINT2、MINT31 和 MLH1 的≧3 个甲基化位点时,确定为 CIMP-高。使用多变量逻辑回归评估危险因素与 CIMP-高 CRC 之间的关联。

结果

与 CIMP-低/阴性 CRC 相比,CIMP-高 CRC 与更多的 IV 期疾病、BRAF V600E 突变和年轻患者(年龄<50 岁)中较高的体重指数(BMI≧27.5kg/m)相关,而在老年患者(年龄≧50 岁)中与更多的右侧肿瘤、BRAF V600E 突变、MSI-高和结直肠息肉相关。多变量分析表明,BMI≧27.5kg/m 在年轻患者中与 CIMP-高 CRC 显著相关。

结论

我们在台湾不同年龄组中确定了 CIMP-高 CRC 的不同临床病理特征。我们的数据表明,BMI≧27.5kg/m 与 50 岁以下患者的 CIMP-高 CRC 之间存在关联。

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