BACKGROUND Oxidatively induced DNA damage, an important factor in cancer etiology, is repaired by oxyguanine glycosylase 1 (OGG1). The lower repair capacity genotype (homozygote Cys326Cys) in the OGG1-rs1052133 (Ser326Cys) polymorphism has been associated with cancer risk. However, no information is available in relation to cancer mortality, other causes of death, and modulation by diet. OBJECTIVE Our aim was to evaluate the association of the OGG1-rs1052133 with total, cancer, and cardiovascular disease (CVD) mortality and to analyze its modulation by the Mediterranean diet, focusing especially on total vegetable intake as one of the main characteristics of this diet. DESIGN Secondary analysis in the PREDIMED (Prevención con Dieta Mediterránea) trial is a randomized, controlled trial conducted in Spain from 2003 to 2010. PARTICIPANTS/SETTING Study participants (n=7,170) were at high risk for CVD and were aged 55 to 80 years. INTERVENTION Participants were randomly allocated to two groups with a Mediterranean diet intervention or a control diet. Vegetable intake was measured at baseline. MAIN OUTCOME MEASURES Main outcomes were all-cause, cancer, and CVD mortality after a median follow-up of 4.8 years. STATISTICAL ANALYSES Multivariable-adjusted Cox regression models were fitted. RESULTS Three hundred eighteen deaths were detected (cancer, n=127; CVD, n=81; and other, n=110). Cys326Cys individuals (prevalence 4.2%) presented higher total mortality rates than Ser326-carriers (P=0.009). The multivariable-adjusted hazard ratio for Cys326Cys vs Ser326-carriers was 1.69 (95% CI 1.09 to 2.62; P=0.018). This association was greater for CVD mortality (P=0.001). No relationship was detected for cancer mortality in the whole population (hazard ratio 1.07; 95% CI 0.47 to 2.45; P=0.867), but a significant age interaction (P=0.048) was observed, as Cys326Cys was associated with cancer mortality in participants <66.5 years (P=0.029). Recessive effects limited our ability to investigate Cys326Cys×diet interactions for cancer mortality. No statistically significant interactions for total or CVD mortality were found for the Mediterranean diet intervention. However, significant protective interactions for CVD mortality were found for vegetable intake (hazard ratio interaction per standard deviation 0.42; 95% CI 0.18 to 0.98; P=0.046). CONCLUSIONS In this population, the Cys326Cys-OGG1 genotype was associated with all-cause mortality, mainly CVD instead of cancer mortality. Additional studies are needed to provide further evidence on its dietary modulation.

中文翻译：

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在 PREDIMED 研究中，DNA 修复 OGG1 基因中 Ser326Cys 多态性对癌症、心血管和全因死亡率的影响：饮食调节

背景氧化诱导的 DNA 损伤是癌症病因学中的一个重要因素，由氧鸟嘌呤糖基化酶 1 (OGG1) 修复。OGG1-rs1052133 (Ser326Cys) 多态性中较低的修复能力基因型（纯合子 Cys326Cys）与癌症风险相关。然而，没有关于癌症死亡率、其他死亡原因和饮食调节的信息。目的 我们的目的是评估 OGG1-rs1052133 与总死亡率、癌症死亡率和心血管疾病 (CVD) 死亡率的关联，并分析地中海饮食对其的调节，特别关注作为这种饮食主要特征之一的蔬菜总摄入量. 设计 PREDIMED (Prevención con Dieta Mediterranea) 试验中的二级分析是 2003 年至 2010 年在西班牙进行的一项随机对照试验。参与者/地点 研究参与者 (n=7,170) 处于 CVD 高风险中，年龄在 55 至 80 岁之间。干预 参与者被随机分配到两组，分别进行地中海饮食干预或控制饮食。在基线测量蔬菜摄入量。主要结局指标 主要结局指标是中位随访 4.8 年后的全因死亡率、癌症死亡率和 CVD 死亡率。统计分析 拟合了多变量调整的 Cox 回归模型。结果 检测到 318 人死亡（癌症，n=127；CVD，n=81；其他，n=110）。Cys326Cys 个体（患病率为 4.2%）的总死亡率高于 Ser326 携带者（P=0.009）。Cys326Cys 与 Ser326 携带者的多变量调整风险比为 1.69（95% CI 1.09 至 2.62；P=0.018）。这种关联对于 CVD 死亡率更大（P=0.001）。未检测到与整个人群的癌症死亡率相关（风险比 1.07；95% CI 0.47 至 2.45；P=0.867），但观察到显着的年龄相互作用（P=0.048），因为 Cys326Cys 与参与者的癌症死亡率相关<66.5 岁（P=0.029）。隐性效应限制了我们研究 Cys326Cys × 饮食相互作用对癌症死亡率的影响。没有发现地中海饮食干预对总死亡率或 CVD 死亡率有统计学意义的相互作用。然而，发现蔬菜摄入对 CVD 死亡率有显着的保护性相互作用（每标准差的风险比相互作用 0.42；95% CI 0.18 至 0.98；P=0.046）。结论 在该人群中，Cys326Cys-OGG1 基因型与全因死亡率相关，主要是心血管疾病而非癌症死亡率。