The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study.
The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study.
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DOI：
10.1186/1471-2407-9-193
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发表时间：
2009-06-18
期刊：
影响因子：
3.8
通讯作者：
Soto JL
中科院分区：
文献类型：
--
作者：
Castillejo A;Mata-Balaguer T;Montenegro P;Ochoa E;Lázaro R;Martínez-Cantó A;Castillejo MI;Guarinos C;Barberá VM;Guillén-Ponce C;Carrato A;Soto JL
转化生长因子-β受体I型是生长抑制信号的中介体。TGFBR16A(Rs11466445)是一种常见的转化生长因子-β受体I基因的多态变异，与肿瘤易感性有关。然而，这种多态作为结直肠癌危险因素的作用是有争议的。这项研究的目的是在西班牙人群中评估TGFBR1*6A与结直肠癌、年龄、性别、肿瘤部位和肿瘤分期的关系。这项病例对照研究涉及800名西班牙受试者：400名散发性结直肠癌患者和400名年龄、性别和种族匹配的对照组。对年龄、性别进行非条件Logistic回归分析，计算TGFBR1*6A基因多态性的优势比(OR)和95%可信区间(95%CI)。分析TGFBR1外显子1 GCG重复序列的体细胞突变和胚系等位基因特异性表达，以进一步了解TGFBR1*6A等位基因在结直肠癌易感性中的作用。TGFBR1*6A等位基因与结直肠癌之间无统计学意义的相关性(p>；0.05)。TGFBR16A等位基因携带者和纯合子TGFBR16A个体的OR值分别为1.147(95%CI：0.799~1.647)和0.878(95%CI：0.306~2.520)。该多态频率不受年龄、性别和肿瘤分期的影响。TGFBR1*6A等位基因在结肠癌患者中的分布明显高于直肠肿瘤患者。69例中仅2例发现肿瘤体细胞突变(2.9%)。这两个病例都涉及GCG缺失，将正常DNA中的9A/9A型改变为9A/8A型。有趣的是，这两个肿瘤的微卫星不稳定性呈阳性，这表明这些突变源于DNA错配修复系统的缺陷。在14例9A/6A杂合子肿瘤中有7例检测到9A等位基因的特异性表达。正如最近提出的，这可能是由于TGFBR1*6A等位基因与导致等位基因特异性表达的突变的连锁不平衡造成的。我们的结果表明，在西班牙人群中，TGFBR1*6A等位基因不会增加患结直肠癌的风险。
TGF-β receptor type I is a mediator of growth inhibitory signals. TGFBR1*6A (rs11466445) is a common polymorphic variant of the TGF-β receptor I gene and has been associated with tumour susceptibility. Nevertheless, the role of this polymorphism as a risk factor for colorectal cancer is controversial. The aim of this study was to assess the association between TGFBR1*6A and colorectal cancer, age, sex, tumour location and tumour stage in a Spanish population. The case-control study involved 800 Spanish subjects: 400 sporadic colorectal cancer patients and 400 age-, sex-, and ethnic-matched controls. The odds ratio (OR) and 95% confidence interval (95% CI) for the TGFBR1*6A polymorphism were calculated using unconditional logistic regression adjusted for age and sex. Analysis of somatic mutations at the GCG repeat of TGFBR1 exon 1 and germline allele-specific expression were also conducted to obtain further information on the contribution of the TGFBR1*6A allele to CRC susceptibility. There was no statistically significant association between the TGFBR1*6A allele and CRC (p > 0.05). The OR was 1.147 (95% CI: 0.799–1.647) for carriers of the TGFBR1*6A allele and 0.878 (95% CI: 0.306–2.520) for homozygous TGFBR1*6A individuals compared with the reference. The frequency of the polymorphism was not affected by age, sex or tumour stage. The TGFBR1*6A allele was more prevalent among colon tumour patients than among rectal tumour patients. Tumour somatic mutations were found in only two of 69 cases (2.9%). Both cases involved a GCG deletion that changed genotype 9A/9A in normal DNA to genotype 9A/8A. Interestingly, these two tumours were positive for microsatellite instability, suggesting that these mutations originated because of a deficient DNA mismatch repair system. Allele-specific expression of the 9A allele was detected in seven of the 14 heterozygous 9A/6A tumour cases. This could have been caused by linkage disequilibrium of the TGFBR1*6A allele with mutations that cause allele-specific expression, as was recently suggested. Our results suggest that the TGFBR1*6A allele does not confer an increased risk of colorectal cancer in the Spanish population.
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影响因子：
2.9
作者：
Kaklamani V;Baddi L;Rosman D;Liu J;Ellis N;Oddoux C;Ostrer H;Chen Y;Ahsan H;Offit K;Pasche B
通讯作者：
Pasche B
影响因子：
6.4
作者：
Castillejo A;Rothman N;Murta-Nascimento C;Malats N;García-Closas M;Gómez-Martínez A;Lloreta J;Tardón A;Serra C;García-Closas R;Chanock S;Silverman DT;Dosemeci M;Kogevinas M;Carrato A;Soto JL;Real FX
通讯作者：
Real FX
影响因子：
20.4
作者：
You, Weiming;Liu, Zeyi;Zhang, Hong-Tao
通讯作者：
Zhang, Hong-Tao
影响因子：
45.3
作者：
Kaklamani, VG;Hou, NJ;Pasche, B
通讯作者：
Pasche, B
DOI：
10.1126/science.1159397
发表时间：
2008-09-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Valle L;Serena-Acedo T;Liyanarachchi S;Hampel H;Comeras I;Li Z;Zeng Q;Zhang HT;Pennison MJ;Sadim M;Pasche B;Tanner SM;de la Chapelle A
通讯作者：
de la Chapelle A