Palli Domenico, Masala Giovanna, Peluso Marco, Gaspari Laura, Krogh Vittorio, Munnia Armelle, Panico Salvatore, Saieva Calogero, Tumino Rosario, Vineis Paolo, Garte Seymour
Molecular and Nutritional Epidemiology Unit and Cancer Risk Factor Branch, Molecular Biology Laboratory-CSPO, Scientific Institute of Tuscany, Florence, Italy.
Carcinogenesis. 2004 Apr;25(4):577-84. doi: 10.1093/carcin/bgh033. Epub 2003 Dec 4.
Frequent consumption of fresh fruit and vegetables, and polymorphisms in the detoxifying enzyme glutathione S-transferase M1 (GSTM1) and other metabolic genes have been shown to modulate cancer risk at some sites. We have shown recently that DNA adducts, a reliable indicator of genotoxic damage and, possibly, of cancer risk, are modulated by plasma levels of selected micronutrients. Here we further investigate the association between DNA adduct levels and consumption of major food groups and foods, and the estimated dietary intake of nutrients, taking into account the possible modifying effect of metabolic polymorphisms, in a larger sample of 634 healthy adults enrolled in a prospective study in Italy. DNA adducts and five polymorphic metabolic genotypes (GSTM1, GSTT1, NAT2, CYP1A1 and MTHFR) were determined in peripheral leukocytes by using 32P-postlabeling technique and PCR methods. DNA bulky adducts (mean: 7.82 +/- 0.40/10(9) nt) were detected in 482/634 samples (76.0%). Overall, DNA adduct levels were significantly and inversely associated with the intake of raw leafy vegetables (P = 0.02), non-citrus fruits (P = 0.04), potassium (P = 0.01) and beta-carotene (P = 0.05). No association was evident with the five genotypes. Stratification by GSTM1 genotype showed strong inverse associations of DNA adduct levels with increasing consumption of all vegetables combined (P = 0.04), leafy vegetables (P = 0.004), raw leafy vegetables (P = 0.002) and fish (P = 0.03) among 307 GSTM1-null subjects; strong inverse associations also emerged with estimated dietary intakes of beta-carotene (P = 0.004), vitamin E (P = 0.004), niacin (P = 0.02) and potassium (P = 0.01). In contrast, no association emerged among 295 subjects with a GSTM1-wild genotype. Overall, statistically significant interactions in predicting DNA adduct levels were observed between the GSTM1-null genotype and consumption of leafy vegetables (P = 0.01), white meat (P = 0.04), and intake of vitamin C (P = 0.04), vitamin E (P = 0.05) and beta-carotene (P = 0.02). Our results suggest that the role of a diet rich in antioxidants in preventing or reducing DNA adduct formation is restricted to subjects lacking the detoxifying activity of GSTM1 isoenzyme (approximately 50% of the general population).
经常食用新鲜水果和蔬菜，以及解毒酶谷胱甘肽S-转移酶M1（GSTM1）和其他代谢基因的多态性已被证明可调节某些部位的癌症风险。我们最近发现，DNA加合物是遗传毒性损伤以及可能的癌症风险的可靠指标，它受特定微量营养素血浆水平的调节。在此，我们在意大利一项前瞻性研究中纳入的634名健康成年人的更大样本中，进一步研究DNA加合物水平与主要食物组和食物的摄入量以及营养素估计膳食摄入量之间的关联，并考虑代谢多态性可能的修饰作用。通过使用32P后标记技术和PCR方法在外周血白细胞中测定DNA加合物和五种多态性代谢基因型（GSTM1、GSTT1、NAT2、CYP1A1和MTHFR）。在634个样本中的482个（76.0%）中检测到DNA大的加合物（平均值：7.82±0.40/10(9)核苷酸）。总体而言，DNA加合物水平与生叶菜类蔬菜（P = 0.02）、非柑橘类水果（P = 0.04）、钾（P = 0.01）和β-胡萝卜素（P = 0.05）的摄入量呈显著负相关。与这五种基因型没有明显关联。按GSTM1基因型分层显示，在307名GSTM1缺失受试者中，DNA加合物水平与所有蔬菜组合（P = 0.04）、叶菜类蔬菜（P = 0.004）、生叶菜类蔬菜（P = 0.002）和鱼类（P = 0.03）的摄入量增加呈强烈负相关；与β-胡萝卜素（P = 0.004）、维生素E（P = 0.004）、烟酸（P = 0.02）和钾（P = 0.01）的估计膳食摄入量也呈强烈负相关。相比之下，在295名具有GSTM1野生型基因型的受试者中没有发现关联。总体而言，在预测DNA加合物水平方面，观察到GSTM1缺失基因型与叶菜类蔬菜（P = 0.01）、白肉（P = 0.04）的摄入量以及维生素C（P = 0.04）、维生素E（P = 0.05）和β-胡萝卜素（P = 0.02）的摄入量之间存在统计学上显著的相互作用。我们的结果表明，富含抗氧化剂的饮食在预防或减少DNA加合物形成方面的作用仅限于缺乏GSTM1同工酶解毒活性的受试者（约占普通人群的50%）。
