TGFbeta1 polymorphism (L10P) and risk of colorectal adenomatous and hyperplastic polyps.

TGFbeta1 polymorphism (L10P) and risk of colorectal adenomatous and hyperplastic polyps.
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TGFbeta1 多态性 (L10P) 与结直肠腺瘤和增生性息肉的风险。

DOI:
10.1093/ije/dyh102
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发表时间:
2004
期刊:
International journal of epidemiology.
影响因子:
--
通讯作者:
Ulrich,CorneliaM
Ulrich,CorneliaM
中科院分区:
--
文献类型:
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作者:
Sparks,Rachel;Bigler,Jeannette;Sibert,JustinG;Potter,JohnD;Yasui,Yutaka;Ulrich,CorneliaM

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背景转化生长因子β1(transforming growth factor-β1,TGF β 1)是一种多功能的信号分子,具有广泛的作用。动物实验表明,TGF β 1在癌变过程中起着双相作用,通过防止良性上皮生长的早期形成,但促进那些生长的恶性转化。TGF β 1基因(L10 P)的信号肽序列的多态性与血浆TGF β 1水平升高的个人与P allele.MethodsWe调查是否这种多态性与结直肠腺瘤性或增生性息肉的风险在明尼苏达州的个人的病例对照研究。结肠直肠息肉的风险分别为个人腺瘤性息肉(n = 513)和增生性息肉(n = 191)相对于息肉的控制(n = 606)使用logistic回归analysis.ResultsNo整体关联之间的L10 P多态性和结肠直肠腺瘤性息肉的风险。与LL基因型个体相比,LP和PP基因型个体发生结直肠增生性息肉的年龄和性别校正比值比(OR)分别为1.0(95%CI:0.7,1.4)和0.7(95%CI:0.4,1.1)。当按吸烟分层时,仅在曾经吸烟者中发现与P等位基因相关的增生性息肉风险降低的证据结论TGF β 1 L10 P基因型与大肠腺瘤的发病风险无关,提示L10 P变异等位基因可能在大肠增生性息肉的发生发展中具有保护作用,可能与其作为上皮生长抑制剂的作用一致。
BackgroundTransforming growth factor-β1 (TGFb1) is a multifunctional signalling molecule with a wide array of roles. Animal experiments suggest that TGFb1 plays a biphasic role in carcinogenesis by protecting against the early formation of benign epithelial growths, but promoting malignant transformation of those growths that do develop. A polymorphism in the signal peptide sequence of theTGFβ1gene (L10P) has been associated with increased levels of plasma TGFb1 in individuals with the P allele.MethodsWe investigated whether this polymorphism was associated with the risk of colorectal adenomatous or hyperplastic polyps in a case-control study of individuals from Minnesota. Risk of colorectal polyps was evaluated separately for individuals with adenomatous polyps (n = 513) and hyperplastic polyps (n = 191) relative to polyp-free controls (n = 606) using logistic regression analysis.ResultsNo overall association was seen between the L10P polymorphism and risk of colorectal adenomatous polyps. The age- and sex-adjusted odds ratios (OR) of developing colorectal hyperplastic polyps were 1.0 (95% CI: 0.7, 1.4) and 0.7 (95% CI: 0.4, 1.1) for individuals with the LP and PP genotypes, respectively, compared with individuals with the LL genotype. When stratified by smoking, evidence for a decreased risk of hyperplastic polyps associated with the P allele was seen only among ever smokers (Pfor trend = 0.05).ConclusionsWhereas adenoma risk did not vary byTGFβ1L10P genotype, these results suggest that the L10P variant allele may have a protective role in the development of colorectal hyperplastic polyps, possibly consistent with its role as an inhibitor of epithelial growths.