Choi Ji-Yeob, Neuhouser Marian L, Barnett Matt, Hudson Matthew, Kristal Alan R, Thornquist Mark, King Irena B, Goodman Gary E, Ambrosone Christine B
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Sts., Buffalo, NY 14263, USA.
Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1115-20. doi: 10.1158/1055-9965.EPI-07-0040.
Oxidative stress, associated with aging and inflammation, is likely to play a role in the etiology of prostate cancer. We evaluated potential associations between gene variants that result in reduced neutralization of reactive oxygen species (ROS; MnSOD Ala-16Val, CAT -262 C>T, and GPX1 Pro200Leu) and prostate cancer risk among 724 men with incident prostate cancer who participated in the Carotene and Retinol Efficacy Trial (CARET) cohort, a randomized trial for the prevention of lung cancer among men with a history of smoking and/or asbestos exposure. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression. Nested case-control analyses included study participants with available DNA (n = 533 cases and 1,470 controls), matched for race, age, and length of follow-time. Overall, there were no associations between genotypes of MnSOD, CAT, and GPX1 and prostate cancer risk, although among men diagnosed before age 65, CAT TT genotype was associated with increased risk (OR, 2.0; 95% CI, 0.97-3.95). Further analyses stratified by factors related to environmental oxidative stress exposures did not modify associations. When calculating the number of risk alleles of MnSOD, CAT, and GPX1 hypothetically related to reduced protection against ROS, there was a nonsignificant relationship between prostate cancer and carriage of five or more risk alleles, in comparison to men with less than five risk alleles (OR, 2.0; 95% CI, 0.90-4.42). In conclusion, it does not seem that variants in MnSOD, CAT, or GPX1 have an influence on prostate cancer risk in this cohort of men who were smokers or exposed to asbestos, although it is possible that cumulative defects in protection from oxidative stress may result in increased risk of the disease.
氧化应激与衰老及炎症相关，可能在前列腺癌的病因学中起作用。我们在724名新发前列腺癌男性中评估了导致活性氧（ROS）中和能力降低的基因变异（锰超氧化物歧化酶Ala-16Val、过氧化氢酶-262 C>T和谷胱甘肽过氧化物酶1 Pro200Leu）与前列腺癌风险之间的潜在关联，这些男性参与了胡萝卜素和视黄醇功效试验（CARET）队列研究，该研究是一项针对有吸烟和/或石棉暴露史男性预防肺癌的随机试验。通过逻辑回归估计比值比（OR）和95%置信区间（95%CI）。巢式病例对照分析纳入了有可用DNA的研究参与者（533例病例和1470例对照），按种族、年龄和随访时间长度进行匹配。总体而言，锰超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶1的基因型与前列腺癌风险之间无关联，尽管在65岁之前确诊的男性中，过氧化氢酶TT基因型与风险增加相关（OR，2.0；95%CI，0.97 - 3.95）。按与环境氧化应激暴露相关的因素分层进行的进一步分析未改变关联。在假设与ROS防护能力降低相关的情况下计算锰超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶1的风险等位基因数量时，与风险等位基因少于5个的男性相比，前列腺癌与携带5个或更多风险等位基因之间存在非显著关系（OR，2.0；95%CI，0.90 - 4.42）。总之，在这个有吸烟或石棉暴露史的男性队列中，锰超氧化物歧化酶、过氧化氢酶或谷胱甘肽过氧化物酶1的变异似乎对前列腺癌风险没有影响，尽管氧化应激防护方面的累积缺陷可能导致疾病风险增加。
