The -9Ala/-9Val polymorphism in the mitochondrial targeting sequence of the manganese superoxide dismutase gene (MnSOD) is associated with age among Hispanics with colorectal carcinoma.
The -9Ala/-9Val polymorphism in the mitochondrial targeting sequence of the manganese superoxide dismutase gene (MnSOD) is associated with age among Hispanics with colorectal carcinoma.
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DOI：
10.3892/or.9.2.235
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发表时间：
2002-03
期刊：
影响因子：
4.2
通讯作者：
J. Stoehlmacher;S. Ingles;D. Park;Wu Zhang;H. Lenz
中科院分区：
文献类型：
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作者：
J. Stoehlmacher;S. Ingles;D. Park;Wu Zhang;H. Lenz
最近，发现了锰超氧化物歧化酶(MnSOD)基因线粒体靶向序列中T到C的替换，将蛋白质的氨基酸序列从Valine(V)改变为Alanine(A)，并与其对氧化应激的防御能力降低有关。我们调查了在西班牙裔和非西班牙裔白人中，MnSOD基因的这种多态是否与结直肠癌风险的增加有关。所有对照组(63名西班牙裔，58名非西班牙裔)和结直肠癌患者(，61名非西班牙裔)用荧光5‘-核酸酶分析进行了基因分型。观察到的丙氨酸频率在无疾病的西班牙裔美国人中为0.62，在非西班牙裔白人对照组中为0.51。在这两个种族中，癌症患者和无疾病对照组之间没有显著差异(p=0.90)，排除了这种多态是西班牙裔和非西班牙裔白人患结直肠癌的危险因素。在西班牙裔结直肠癌患者中，丙氨酸等位基因在年轻患者中更常见。丙氨酸纯合子(24/)患者的平均年龄为37.6岁，杂合子患者(29/)的平均年龄为42.3岁，V等位基因纯合子患者的平均年龄为48.4岁(p=0.045，ANOVA)。数据表明，-9Val/-9Ala替换在西班牙裔美国人中比在非西班牙裔白人中更常见。此外，数据表明，这种多态的丙氨酸等位基因可能与拉美裔美国人在年轻时患结直肠癌的风险增加有关。
Recently a T to C substitution in the mitochondrial targeting sequence of the manganese superoxide dismutase (MnSOD) gene was observed that changes the amino acid sequence of the protein from valine (V) to alanine (A) and is associated with a decreased defense capacity against oxidative stress. We investigated whether this polymorphism of the MnSOD gene is associated with increased risk for colorectal cancer among Hispanics and non-Hispanic whites. All controls (63 Hispanic, 58 non-Hispanic) and colorectal cancer cases (64 Hispanic, 61 non-Hispanic) were genotyped using a fluorogenic 5'-nuclease assay. The observed alanine frequency was 0.62 among disease-free Hispanics and 0.51 among non-Hispanic whites controls. No significant differences were observed between cancer patients and disease-free controls in either ethnic group (p=0.90) excluding this polymorphism as a risk factor for colorectal cancer in Hispanics and non-Hispanic whites. Among Hispanic individuals with colorectal cancer the alanine allele was observed more frequently in young patients. Patients homozygous for the alanine allele (24/64) showed a mean age of 37.6 years compared to 42.3 years for heterozygotes (29/64) and 48.4 years for patients homozygous for the V allele (p=0.045, ANOVA). The data demonstrate that the -9Val/-9Ala substitution is more common in Hispanics than in non-Hispanic whites. Furthermore, the data suggest that the alanine allele of this polymorphism may be associated with an increased risk to develop colorectal cancer at a young age in Hispanics.