Influence of the C161T but not Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma on colorectal cancer in an Indian population

Influence of the C161T but not Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma on colorectal cancer in an Indian population
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DOI:
10.1111/j.1349-7006.2005.00072.x
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发表时间:
2005-08-01
期刊:
影响因子:
5.7
通讯作者:
Tokudome, S
Tokudome, S
中科院分区:
医学2区
文献类型:
--
作者:
Jiang, J;Gajalakshmi, V;Tokudome, S

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本研究的目的是调查过氧化物酶体增殖物激活受体-γ (PPAR-γ) 基因中的 Pro12AIa 和 C161T 多态性与结直肠癌(CRC 风险)之间的关联。1999 年至 2001 年,我们在印度钦奈的马德拉斯癌症研究所招募了 301 名新诊断的 CRC 患者和 291 名健康对照受试者。Pro12AIa 的基因型使用 PCR-RFLP 方法确定 C161T 和 C161T 多态性,调整年龄、性别、吸烟习惯、家族史和家庭收入后,与 C161T 多态性的 C/C 基因型相比,观察到 C/T + T/T 基因型患 CRC 的风险增加(比值比 = 1.61,95% 置信区间:1.10-2.36),而 Pro12AIa 没有发现显着关联。 (比值比 = 1.06,95% 置信区间:0.70-1.61)。估计单倍型分析显示,病例和对照之间的单倍型频率存在显着差异(chi(2) = 11.62,P = 0.009,d.f. = 3)。尽管观察到的关联的生物学机制仍然存在,但两种多态性与 CRC 风险之间的关系并未发生显着改变。需要阐明的是,我们的研究结果表明 PPAR-gamma 基因的 C161T 多态性与 CRC 的风险相关,需要进一步研究以探讨 PPAR-gamma 基因多态性在 CRC 发生中的功能意义。
The aim of the present study was to investigate associations between Pro12AIa and C161T polymorphisms in the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) gene and colorectal cancer (CRC risk. We recruited 301 newly diagnosed CRC patients and 291 healthy control subjects at the Madras Cancer Institute in Chennai, India, from 1999 to 2001. Genotypes of the Pro12AIa and C161T polymorphisms were determined using the PCR-RFLP method. After adjustment for age, sex, smoking habit, family history and family income, an increased risk of CRC was observed for the C/T + T/T genotype compared to the C/C genotype of the C161T polymorphism (odds ratio = 1.61, 95% confidence interval: 1.10-2.36), whereas no significant association was found for Pro12AIa (odds ratio = 1.06, 95% confidence interval: 0.70-1.61). Analysis with estimated haplotypes showed a significant difference in haplotype frequencies between cases and controls (chi(2) = 11.62, P = 0.009, d.f. = 3). The relationship between the two polymorphisms and CRC risk was not significantly modified by dietary intake of fish. Although the biological mechanisms of the observed association remain to be elucidated, our findings suggest that the C161T polymorphism of the PPAR-gamma gene is related to risk of CRC. Further research is needed to investigate functional implications of polymorphisms of the PPAR-gamma gene in CRC development.