Gunter Marc J, Divi Rao L, Kulldorff Martin, Vermeulen Roel, Haverkos Kathryn J, Kuo Maryanne M, Strickland Paul, Poirier Miriam C, Rothman Nathaniel, Sinha Rashmi
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Division of Health and Human Services, Bethesda, MD 20852, USA.
Carcinogenesis. 2007 Jul;28(7):1426-9. doi: 10.1093/carcin/bgm022. Epub 2007 Feb 2.
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 (+/-)-7beta,8alpha-dihydroxy-9alpha,10alpha-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 10(8) 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.
食用炭烤红肉和肉类衍生的多环芳烃(PAHs)与结直肠癌的前驱病变——大肠腺瘤的风险相关。此外,已有研究表明,白细胞PAH-DNA加合物水平会因摄入炭烤红肉而升高,但迄今为止,尚无研究探讨白细胞PAH-DNA加合物水平与大肠腺瘤风险之间的关系。我们在一项基于临床的大肠腺瘤病例对照研究中,调查了白细胞PAH-DNA加合物形成与大肠腺瘤之间的关系。该研究包括82例大肠腺瘤病例和111例无息肉对照,他们均非当前吸烟者。采用一种敏感的化学发光免疫分析法,使用针对用(±)-7β,8α-二羟基-9α,10α-环氧-7,8,9,10-四氢苯并[a]芘修饰的DNA产生的抗血清来测量白细胞PAH-DNA加合物,该抗血清可识别与人类DNA结合的几种PAHs。大肠腺瘤病例的白细胞PAH-DNA加合物水平(中位数为每10⁸个核苷酸1.4个加合物)高于无息肉对照(中位数为每10⁸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之间存在正相关:PAH-DNA加合物水平每增加一个单位(每10⁸个核苷酸),比值比(OR)为1.5 [95%置信区间(CI),1.1 - 2.2]。此外,将PAH-DNA加合物水平最低四分位数与最高四分位数进行比较,大肠腺瘤风险的OR为2.8(95% CI,1.2 - 6.5;P(趋势) = 0.048)。这些数据支持PAH暴露与大肠腺瘤之间存在联系。