Department of Public Health Sciences, Henry Ford Health System, Detroit, MI 48202, USA.
Cancer Prev Res (Phila). 2011 Oct;4(10):1636-44. doi: 10.1158/1940-6207.CAPR-11-0100. Epub 2011 Aug 16.
In humans, genetic variation and dietary factors may alter the biological effects of exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the major heterocyclic amines generated from cooking meats at high temperatures that has carcinogenic potential through the formation of DNA adducts. Previously, we reported grilled red meat consumption associated with PhIP-DNA adduct levels in human prostate. In this study, we expanded our investigation to estimate the associations between beverage consumption and PhIP-DNA adduct levels in prostate for 391 prostate cancer cases. Of the 15 beverages analyzed, red wine consumption had the strongest association with PhIP-DNA adduct levels showing an inverse correlation in both tumor (P = 0.006) and nontumor (P = 0.002) prostate cells. Red wine consumption was significantly lower in African American compared with white cases, but PhIP-DNA adduct levels in prostate did not vary by race. In African Americans compared with whites, however, associations between red wine consumption and PhIP-DNA adduct levels were not as strong as associations with specific (e.g., SULT1A1 and UGT1A10 genotypes) and nonspecific (e.g., African ancestry) genetic variation. In a multivariable model, the covariate for red wine consumption explained a comparable percentage (13%-16%) of the variation in PhIP-DNA adduct levels in prostate across the two racial groups, but the aforementioned genetic factors explained 33% of the PhIP-DNA adduct variation in African American cases, whereas only 19% of the PhIP-DNA adduct variation in whites. We conclude that red wine consumption may counteract biological effects of PhIP exposure in human prostate, but genetic factors may play an even larger role, particularly in African Americans.
在人类中，遗传变异和饮食因素可能会改变暴露于 2-氨基-1-甲基-6-苯基咪唑[4,5-b]吡啶（PhIP）的生物学效应，PhIP 是在高温下烹饪肉类时产生的主要杂环胺之一，具有致癌潜力，可通过形成 DNA 加合物。此前，我们报告了烧烤红肉的消费与人类前列腺中 PhIP-DNA 加合物水平有关。在这项研究中，我们扩大了调查范围，以估计 391 例前列腺癌病例中前列腺中饮料消费与 PhIP-DNA 加合物水平之间的关联。在分析的 15 种饮料中，红酒消费与 PhIP-DNA 加合物水平的相关性最强，在肿瘤（P=0.006）和非肿瘤（P=0.002）前列腺细胞中均呈负相关。与白人病例相比，非裔美国人的红酒消费明显较低，但前列腺中的 PhIP-DNA 加合物水平不因种族而异。然而，与白人相比，在非裔美国人中，红酒消费与 PhIP-DNA 加合物水平之间的关联不如与特定（例如，SULT1A1 和 UGT1A10 基因型）和非特定（例如，非洲血统）遗传变异之间的关联强。在多变量模型中，红酒消费的协变量解释了两组人群前列腺中 PhIP-DNA 加合物水平变化的可比比例（13%-16%），但上述遗传因素解释了非裔美国人病例中 33%的 PhIP-DNA 加合物变异，而在白人中仅占 19%。我们得出结论，红酒消费可能会抵消 PhIP 暴露对人类前列腺的生物学效应，但遗传因素可能发挥更大的作用，尤其是在非裔美国人中。
