Allele-specific expression of TGFBR1 in colon cancer patients.
Allele-specific expression of TGFBR1 in colon cancer patients.
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DOI：
10.1093/carcin/bgq165
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发表时间：
2010-10
期刊：
影响因子：
4.7
通讯作者：
de la Chapelle A
中科院分区：
文献类型：
--
作者：
Tomsic J;Guda K;Liyanarachchi S;Hampel H;Natale L;Markowitz SD;Tanner SM;de la Chapelle A
结直肠癌（CRC）易感性的遗传成分仅得到部分解释。我们最近提出，TGFBR1基因的一个等位基因表达的轻微下降是一种易患结直肠癌的遗传数量性状。在这里，我们改进了TGFBR1等位基因特异性表达（ASE）在基于人群的CRC患者和对照组中的测量。对该基因3 ' -非翻译区5个单核苷酸多态性（snp）进行基因分型，并利用焦磷酸测序法测定ASE。在剔除无信息样本和RNA质量不足样本后，109例病例和125例对照进行了研究。等位基因比率在0.74至1.69之间，没有证据表明“ASE”与“非ASE”存在双峰性或截止点。将ASE作为连续变量，病例值与对照组无显著差异（P = 0.081）。然而，当使用排列检验比较中位数（P = 0.0027）和使用Wilcoxon检验（P = 0.0094）时，病例的ASE值明显较高。我们的结论是，以目前的技术，个体之间以及病例和对照组之间的ASE差异太微小，无法用于评估结直肠癌的风险。更先进的技术有望解决这一问题，以及由转录snp的有限杂合性引起的低信息性。
The genetic component of colorectal cancer (CRC) predisposition has been only partially explained. We recently suggested that a subtle decrease in the expression of one allele of the TGFBR1 gene was a heritable quantitative trait predisposing to CRC. Here, we refined the measurements of allele-specific expression (ASE) of TGFBR1 in a population-based series of CRC patients and controls. Five single-nucleotide polymorphisms (SNPs) in the 3′-untranslated region of the gene were genotyped and used for ASE determination by pyrosequencing. After eliminating non-informative samples and samples with RNA of insufficient quality 109 cases and 125 controls were studied. Allelic ratios ranged between 0.74 and 1.69 without evidence of bimodality or cutoff points for ‘ASE’ versus ‘non-ASE’. Treating ASE as a continuous variable, cases had non-significantly different values than controls (P = 0.081 when comparing means by permutation test). However, cases had significantly higher ASE values when comparing medians by permutation test (P = 0.0027) and when using Wilcoxon test (P = 0.0094). We conclude that with the present-day technology, ASE differences between individuals and between cases and controls are too subtle to be used to assess CRC risk. More advanced technology is expected to resolve this issue as well as the low informativity caused by the limited heterozygosity of transcribed SNPs.
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影响因子：
7
作者：
Lo, HS;Wang, ZN;Lee, MP
通讯作者：
Lee, MP
影响因子：
158.5
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Pomerantz, Mark M.;Ahmadiyeh, Nasim;Jia, Li;Herman, Paula;Verzi, Michael P.;Doddapaneni, Harshavardhan;Beckwith, Christine A.;Chan, Jennifer A.;Hills, Adam;Davis, Matt;Yao, Keluo;Kehoe, Sarah M.;Lenz, Heinz-Josef;Haiman, Christopher A.;Yan, Chunli;Henderson, Brian E.;Frenkel, Baruch;Barretina, Jordi;Bass, Adam;Tabernero, Josep;Baselga, Jose;Regan, Meredith M.;Manak, J. Robert;Shivdasani, Ramesh;Coetzee, Gerhard A.;Freedman, Matthew L.
通讯作者：
Freedman, Matthew L.