首页> 外文期刊>Carcinogenesis >The effect of the cyclin D1 (CCND1) A870G polymorphism on colorectal cancer risk is modified by glutathione-S-transferase polymorphisms and isothiocyanate intake in the Singapore Chinese Health Study
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The effect of the cyclin D1 (CCND1) A870G polymorphism on colorectal cancer risk is modified by glutathione-S-transferase polymorphisms and isothiocyanate intake in the Singapore Chinese Health Study

机译:在《新加坡华人健康研究》中,谷胱甘肽-S-转移酶多态性和异硫氰酸盐的摄入改变了细胞周期蛋白D1(CCND1)A870G多态性对大肠癌风险的影响。

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摘要

Cyclin D1 (CCND1) regulates cellular decision between proliferation and growth arrest. Despite the functional relevance of the CCND1 A870G single nucleotide polymorphism (SNP) published results on its association with colorectal cancer (CRC) were inconsistent. We examined the association between this CCND1 genotype and CRC in the Singapore Chinese Health Study, a prospective investigation of diet and cancer in 63 000 Chinese men and women. We explored the hypothesis that inconsistency regarding the CCND1/CRC association may be attributable to the modifying effect of additional CRC risk factors. Since GSTM1/GSTT1 genotype and dietary isothiocyanate (ITC) intake had previously been identified as CRC risk factors in this cohort, we now explored if they influenced the CCND1/CRC association. In a nested case–control study within the Singapore Cohort, genomic DNA collected from 300 incident CRC cases and 1169 controls was examined for CCND1, GSTM1, GSTT1 and GSTP1 polymorphisms. Unconditional logistic regression was used to assess genotype effects on cancer risk. No main effect of CCND1 was observed, yet the CCND1 effect was influenced by ITC intake and GST genotypes. The presence of at least one CCND1 A-allele was associated with increased risk among low dietary ITC consumers (intake below median value for the cohort) with a high-activity GST profile (≥2 of the 3 GST genotypes classified non-null or high-activity) [odds ratio (OR) = 2.05; 95% confidence interval (CI), 1.10–3.82]. In contrast, the presence of at least one A-allele was associated with a decreased risk among all remaining subjects (OR = 0.56; 0.36–0.86) (P for interaction = 0.01). Recent studies indicate that ITCs inhibit cell proliferation and cause apoptosis through pro-oxidant properties. The results of our current study on CRC and those of our previous breast cancer study are compatible with the notion of oxidative stress in target cells as important determinant of direction and magnitude of the CCND1 effect.
机译:细胞周期蛋白D1(CCND1)调节增殖和生长停滞之间的细胞决定。尽管CCND1 A870G具有单核苷酸多态性(SNP)的功能相关性,但已发表的有关其与结直肠癌(CRC)关联的结果不一致。我们在《新加坡华人健康研究》中研究了CCND1基因型与CRC之间的关联,该研究是对63 000名中国男女饮食和癌症的一项前瞻性调查。我们探讨了以下假设:关于CCND1 / CRC关联的不一致可能归因于其他CRC风险因素的修正作用。由于先前已将GSTM1 / GSTT1基因型和膳食异硫氰酸盐(ITC)摄入量确定为该人群的CRC危险因素,因此我们现在探讨它们是否影响CCND1 / CRC关联。在新加坡队列的嵌套病例对照研究中,检查了从300例CRC病例和1169例对照中收集的基因组DNA的CCND1,GSTM1,GSTT1和GSTP1多态性。使用无条件逻辑回归来评估基因型对癌症风险的影响。没有观察到CCND1的主要作用,但是CCND1的作用受ITC摄入量和GST基因型的影响。具有高活性GST谱(≥3种分类为非无效或高的GST基因型中的2种)的低饮食ITC消费者中摄入至少一种CCND1 A等位基因与风险增加相关(该队列的摄入低于中值) -活性)[几率(OR)= 2.05; 95%置信区间(CI),1.10–3.82]。相反,在所有其余受试者中,至少有一个A等位基因的存在与降低的风险相关(OR = 0.56; 0.36-0.86)(相互作用的P = 0.01)。最近的研究表明,ITC通过促氧化剂特性抑制细胞增殖并引起细胞凋亡。我们目前对CRC的研究结果以及我们先前对乳腺癌的研究结果与靶细胞中氧化应激的概念相吻合,这是CCND1效应的方向和强度的重要决定因素。

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  • 来源
    《Carcinogenesis》 |2006年第12期|2475-2482|共8页
  • 作者单位

    Molecular Epidemiology/Cancer Registry Institutes of Social and Preventive Medicine/Surgical Pathology University Hospital Zürich Zürich Switzerland;

    The Cancer Center University of Minnesota Minneapolis MN 55455 USA;

    USC/Norris Comprehensive Cancer Center University of Southern California Los Angeles CA 90033 USA;

    Department of Community Occupational and Family Medicine National University of Singapore Singapore 117597;

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