Diagnostic strategy to improve the efficiency of screening diabetes—ROC analysis for fasting plasma glucose

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【作者】 Junxi Lu  Weiping Jia  Lei Chen  Yuanmin Wu  Yuhua Zuo  Kunsan Xiang 

【关键词】Esophageal cancer  Polymorphism  EPHX1 

【出版日期】2008-01-01

【摘要】Genetic polymorphisms in xenobiotic metabolizing enzymes may alter risk of various cancers. Present case-control study evaluated the influence of <i>EPHX1</i> genetic variations on squamous cell esophageal cancer (ESCC) susceptibility in 107 patients and 320 controls. <i>EPHX1</i> polymorphic alleles were genotyped by direct sequencing (exon 3, <i>Tyr113His</i>) or PCR-RFLP (exon 4, <i>His139Arg</i>). Patients with exon 3 genotypes (<i>Tyr113His, His113His</i>) and 113His allele were at risk of ESCC (OR<sub><i>Tyr113His</i></sub> 2.0, 95%CI = 1.2&#x2013;3.4, <i>p</i> = 0.007; OR<sub><i>His113His</i></sub> 2.3 95%CI = 1.0&#x2013;5.2, <i>p</i> = 0.03 and OR<sub><i>His</i></sub> 1.5, 95%CI = 1.0&#x2013;2.1, <i>p</i> = 0.01). In contrast, individuals with exon 4, <i>139Arg</i> allele were at low risk of cancer (OR 0.34, 95%CI = 0.20&#x2013;0.56, <i>p</i> = 0.001). However, none of haplotype combinations of exon 3 (<i>Tyr113His</i>) and exon 4 (<i>His139Arg</i>) polymorphisms showed modulation of risk for ESCC. Sub-grouping of patients based on anatomical location of tumor predicted that patients with exon 3, <i>His113His</i> and <i>Tyr113His</i> genotypes were at higher risk for developing ESCC tumor at upper and middle third locations (OR 4.4, 95%CI = 1.0&#x2013;18.5, <i>p</i> = 0.04; OR 2.5, 95%CI = 1.3&#x2013;5.0, <i>p</i> = 0.005 respectively). The frequency of exon 4, <i>His139Arg</i> genotype was significantly lower in ESCC patients with lower third tumor location as compared to controls (14.8%vs. 36.3%, <i>p</i> = 0.02). In case-only study, gene-environment interaction of <i>EPHX1</i> genotypes with tobacco, alcohol and occupational exposures did not appear to modulate the cancer susceptibility. In conclusion, exon 3, <i>Tyr113His</i> genotype was associated with higher risk of ESCC particularly at upper and middle-third anatomical locations of tumor. However, <i>His139Arg</i> genotype of exon 4, exhibited low risk for ESCC as well as its clinical characteristics.

【刊名】Diabetes Research and Clinical Practice

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