Leukocyte polycyclic aromatic hydrocarbon-DNA adduct formation and colorectal adenoma

Leukocyte polycyclic aromatic hydrocarbon-DNA adduct formation and colorectal adenoma
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DOI:
10.1093/carcin/bgm022
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发表时间:
2007-07-01
期刊:
影响因子:
4.7
通讯作者:
Sinha, Rashmi
Sinha, Rashmi
中科院分区:
医学2区
文献类型:
--
作者:
Gunter, Marc J.;Divi, Rao L.;Sinha, Rashmi

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食用炭烤红肉和肉类衍生的多环芳烃(PAHs)与结直肠腺瘤(结直肠癌的前兆)的风险有关。此外,白细胞PAH-DNA加合物水平已被证明会增加对烧烤红肉摄入量的反应,但迄今为止还没有研究调查白细胞PAH-DNA加合物水平与结直肠腺瘤风险之间的关系。我们在一项以临床为基础的结直肠腺瘤病例对照研究中探讨了白细胞多环芳烃-DNA加合物形成与结直肠腺瘤的关系。该研究包括82例结直肠腺瘤和111例无息肉对照,其中没有一人目前吸烟。白细胞PAH-DNA加合物通过灵敏的化学发光免疫测定法测量,使用抗血清,该抗血清针对经(+/-)-7 β,8 α-二羟基-9 α,10 α-环氧-7,8,9,10-四氢-苯并[a]芘修饰的DNA,其识别与人DNA结合的几种PAH。结直肠腺瘤患者的白细胞PAH-DNA加合物水平(中位数,每10(8)个核苷酸1.4个加合物)高于无息肉对照组(中位数,每10(8)个核苷酸1.2个加合物)(P = 0.02)。PAH-DNA加合物水平与腺瘤患病率呈正相关:PAH-DNA加合物水平(每108个核苷酸)每增加一个单位,比值比(OR)为1.5 [95%置信区间(CI),1.1-2.2]。此外,PAH-DNA加合物水平的最低四分位数与最高四分位数的比较得出结直肠腺瘤风险的OR为2. 8(95% CI,1. 2 - 6. 5; P趋势= 0. 048)。这些数据支持PAH暴露与结直肠腺瘤之间的联系。
Consumption of charbroiled red meat and meat-derived polycyclic aromatic hydrocarbons (PAHs) has been associated with risk of colorectal adenoma, a precursor of colorectal cancer. Furthermore, leukocyte PAH-DNA adduct levels have been demonstrated to increase in response to charbroiled red meat intake but to date there have been no studies that have investigated the relationship between leukocyte PAH-DNA adduct levels and risk of colorectal adenoma. We investigated the relation of leukocyte PAH-DNA adduct formation and colorectal adenoma in a clinic-based case-control study of colorectal adenomas. The study comprised 82 cases of colorectal adenoma and 111 polyp-free controls, none of whom were current smokers. Leukocyte PAH-DNA adducts were measured by a sensitive chemiluminescence immunoassay using an antiserum elicited against DNA modified with (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene that recognizes several PAHs bound to human DNA. Leukocyte PAH-DNA adduct levels were higher among colorectal adenoma cases (median, 1.4 adducts per 10(8) nucleotides) than polyp-free controls (median, 1.2 adducts per 10(8) nucleotides) (P = 0.02). There was a positive association between PAH-DNA adduct level and adenoma prevalence: each unit increase in PAH-DNA adduct level (per 108 nucleotides) was associated with an odds ratio (OR) of 1.5 [95% confidence interval (CI), 1.1-2.2]. In addition, a comparison of the lowest quartile for PAH-DNA adduct level with the highest quartile yielded an OR of 2.8 (95% CI, 1.2-6.5; P-trend = 0.048) for risk of colorectal adenoma. These data support a link between PAH exposure and colorectal adenoma.