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8q24.21 rs10505477-rs6983267单倍型与结直肠癌诊断年龄的关联

Association of 8q24.21 rs10505477-rs6983267 haplotype and age at diagnosis of colorectal cancer.

作者信息

Haerian Monir Sadat, Haerian Batoul Sadat, Rooki Hassan, Molanaei Saadat, Kosari Farid, Obohhat Maedeh, Hosseinpour Parisa, Azimzadeh Pedram, Mohebbi Seyed Reza, Akbari Zahra, Zali Mohammad Reza

机构信息

Gastroenterology and Liver Diseases Research Center (GLDRC), Shahid Beheshti University of Medical Science, Tehran, Iran E-mail :

出版信息

Asian Pac J Cancer Prev. 2014;15(1):369-74. doi: 10.7314/apjcp.2014.15.1.369.

Abstract

BACKGROUND

Colorectal cancer (CRC) is the fourth most common cause of cancer death in the world. Genetic variants in 8q24.21 including rs10505477 and rs6983267 have been hypothesized to be involved in susceptibility to CRC. This study aims to investigate the possible association between these loci and their haplotypes with CRC risk in Iranian population.

MATERIALS AND METHODS

Subjects were recruited from two hospitals in Tehran. The rs10505477 and rs6983267 polymorphisms were genotyped by TaqMan real time PCR using subject genomic DNA, extracted either from formalin-fixed, paraffin-embedded tissue of patients or from blood of the controls by standard methods.

RESULTS

A total of 715 subjects (380 CRC patients and 335 matched controls) were genotyped in this study. Allele and genotype analysis of the rs10505477 and rs6983267 polymorphisms by gender, age at diagnosis, tumor location, tumor grade, and tumor node metastasis (TNM) showed no significant association with CRC risk. There was a significant relationship between GG haplotype and susceptibility to age at diagnosis for both <60 and ≥60 (p=0.0005 and p=0.000004, respectively) and between GT and CRC in the age at diagnosis ≥ 60 (Table 3: p=0.031). The GG haplotype was less frequent in CRC patients with the age at diagnosis <60, but was more common in subjects with the age at diagnosis ≥ 60.

CONCLUSIONS

Results of this study suggests that the rs6983267 and rs10505477 polymorphisms alone may not be relevant to CRC risk, but their GG haplotype plays a notable role in age at diagnosis of CRC in the Iranian population.

摘要

背景

结直肠癌(CRC)是全球第四大常见癌症死因。据推测,8q24.21区域的基因变异,包括rs10505477和rs6983267,与CRC易感性有关。本研究旨在调查这些基因座及其单倍型与伊朗人群CRC风险之间的可能关联。

材料与方法

研究对象来自德黑兰的两家医院。采用TaqMan实时荧光定量PCR技术,使用从患者福尔马林固定、石蜡包埋组织或对照者血液中通过标准方法提取的基因组DNA,对rs10505477和rs6983267多态性进行基因分型。

结果

本研究共对715名受试者(380例CRC患者和335例匹配对照)进行了基因分型。按性别、诊断时年龄、肿瘤位置、肿瘤分级和肿瘤淋巴结转移(TNM)对rs10505477和rs6983267多态性进行等位基因和基因型分析,结果显示与CRC风险无显著关联。GG单倍型与诊断时年龄<60岁和≥60岁的易感性均存在显著关系(分别为p = 0.0005和p = 0.000004),GT与诊断时年龄≥60岁的CRC存在显著关系(表3:p = 0.031)。GG单倍型在诊断时年龄<60岁的CRC患者中频率较低,但在诊断时年龄≥60岁的受试者中更为常见。

结论

本研究结果表明,单独的rs6983267和rs10505477多态性可能与CRC风险无关,但其GG单倍型在伊朗人群CRC诊断年龄中起显著作用。

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