Mikhak Bahar, Hunter David J, Spiegelman Donna, Platz Elizabeth A, Wu Kana, Erdman John W, Giovannucci Edward
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Carcinogenesis. 2008 Dec;29(12):2335-40. doi: 10.1093/carcin/bgn212. Epub 2008 Sep 10.
The manganese superoxide dismutase (MnSOD) gene encodes an antioxidant enzyme (SOD2) that may protect cells from oxidative damage. The MnSOD allele with Val as amino acid 16 encodes a protein that has 30-40% lower activity compared with the MnSOD Ala variant, hence possibly increasing susceptibility to oxidative stress. On the other hand, some epidemiologic studies suggest that the Ala allele is associated with a higher risk of cancer, including prostate cancer.
We conducted a nested case-control study in the Health Professionals Follow-up Study with 612 incident prostate cancer cases and 612 matched controls to investigate the role of the MnSOD gene Ala16Val polymorphism and its joint association with plasma carotenoid concentrations in relation to risk of total prostate cancer and aggressive prostate cancer (advanced stage or Gleason sum > or =7).
The allele frequencies in the controls were 49.8% for Ala and 50.2% for Val. No association was found between the MnSOD genotype and risk of total and aggressive prostate cancer. Furthermore, no statistically significant interaction was observed between the MnSOD genotype and any of the plasma carotenoids in relation to risk of total and aggressive prostate cancer. In analyses in which we combined data from plasma and dietary carotenoids and created a quintile score to reflect long-term carotenoid status, a 3-fold [95% confidence interval: 1.37-7.02] increased risk of aggressive prostate cancer was observed among men with the Ala/Ala genotype in the presence of low long-term lycopene status (P-value, test for interaction = 0.02) as compared with men with the Ala/Val+Val/Val genotypes with low long-term lycopene status.
In this cohort of mainly white men, the MnSOD gene Ala16Val polymorphism was not associated with total or aggressive prostate cancer risk. However, men with the MnSOD Ala/Ala genotype who had low long-term lycopene status had a higher risk of aggressive prostate cancer compared with individuals with the other genotypes. These results are consistent with findings from earlier studies that reported when antioxidant status is low, the MnSOD Ala/Ala genotype may be associated with an increased risk of aggressive prostate cancer.
锰超氧化物歧化酶（MnSOD）基因编码一种抗氧化酶（SOD2），它可能保护细胞免受氧化损伤。第16位氨基酸为缬氨酸（Val）的MnSOD等位基因所编码的蛋白质，其活性比丙氨酸（Ala）变体的MnSOD低30%-40%，因此可能增加对氧化应激的易感性。另一方面，一些流行病学研究表明Ala等位基因与包括前列腺癌在内的癌症风险较高有关。
我们在健康专业人员随访研究中开展了一项巢式病例对照研究，有612例前列腺癌新发病例和612例匹配对照，以调查MnSOD基因Ala16Val多态性的作用及其与血浆类胡萝卜素浓度的联合关联与前列腺癌总体风险和侵袭性前列腺癌（晚期或Gleason评分≥7）风险的关系。
对照中Ala等位基因频率为49.8%，Val等位基因频率为50.2%。未发现MnSOD基因型与前列腺癌总体风险和侵袭性风险之间存在关联。此外，在前列腺癌总体风险和侵袭性风险方面，未观察到MnSOD基因型与任何血浆类胡萝卜素之间存在统计学显著的相互作用。在我们合并血浆和膳食类胡萝卜素数据并创建一个五分位数评分以反映长期类胡萝卜素状态的分析中，与长期番茄红素水平低且为Ala/Val+Val/Val基因型的男性相比，长期番茄红素水平低且为Ala/Ala基因型的男性发生侵袭性前列腺癌的风险增加了3倍[95%置信区间：1.37-7.02]（交互作用检验的P值=0.02）。
在这个主要为白人男性的队列中，MnSOD基因Ala16Val多态性与前列腺癌总体风险或侵袭性风险无关。然而，与其他基因型个体相比，长期番茄红素水平低且为MnSOD Ala/Ala基因型的男性发生侵袭性前列腺癌的风险更高。这些结果与早期研究结果一致，早期研究报告当抗氧化状态较低时，MnSOD Ala/Ala基因型可能与侵袭性前列腺癌风险增加有关。
