Polymorphisms in mitochondrial genes and prostate cancer risk.
Polymorphisms in mitochondrial genes and prostate cancer risk.
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DOI：
10.1158/1055-9965.epi-08-0434
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Thibodeau SN
中科院分区：
文献类型：
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作者：
Wang L;McDonnell SK;Hebbring SJ;Cunningham JM;St Sauver J;Cerhan JR;Isaya G;Schaid DJ;Thibodeau SN
线粒体，传统上被认为是能量代谢特有的细胞器，实际上是多功能的，与包括癌症在内的许多疾病有关。为了评估线粒体相关基因是否与前列腺癌风险增加相关，我们对线粒体基因组中的24个单核苷酸多态(SNPs)和376个标签SNPs进行了基因分型，这些SNPs定位于78个核编码的线粒体基因。根据连锁不平衡原理，选择≥覆盖率达到80%的Tag SNPs。我们比较了约1000例前列腺癌患者和约500例对照人群的等位基因和单倍型频率。当使用全球得分统计进行评估时，没有检测到任何单独的mtSNPs或10个线粒体常见单倍型与前列腺癌的关联。对于核编码基因，在调整多次测试后，没有一个标签SNP与前列腺癌显著相关。尽管如此，我们通过将我们的结果与CGEMS第一阶段数据集的结果进行比较来评估未调整的p值。在我们的数据和CGE MS中，有7个标签SNP具有未调整的p值≤0.05(其中2个SNP与CGE MS SNP相同，5个与CGE MS SNP存在强烈连锁不平衡)。这7个SNP(rs17184211、rs4147684、rs4233367、rs2070902、rs3829037、rs7830235和rs1203213)分别位于mtrr、NDUFA9、NDUFS2、NDUFB9和COX7A2基因上。七个SNPs中的五个进一步包括在CGEMS第二阶段研究中，然而，这些研究的结果都没有重复。总体而言，这些结果表明，线粒体基因组和核编码线粒体基因的多态并不是前列腺癌的主要风险因素。
The mitochondrion, conventionally thought to be an organelle specific to energy metabolism, is in fact multi-functional and implicated in many diseases, including cancer. To evaluate whether mitochondria-related genes are associated with increased risk for prostate cancer, we genotyped 24 single nucleotide polymorphisms (SNPs) within the mitochondrial genome (mtSNPs) and 376 tagSNPs localized to 78 nuclear-encoded mitochondrial genes. The tagSNPs were selected to achieve ≥80% coverage based on linkage disequilibrium. We compared allele and haplotype frequencies in ~1000 prostate cancer cases with ~500 population controls. An association with prostate cancer was not detected for any of the mtSNPs individually or for 10 mitochondrial common haplotypes when evaluated using a global score statistic. For the nuclear-encoded genes, none of the tagSNPs were significantly associated with prostate cancer after adjusting for multiple testing. Nonetheless, we evaluated unadjusted p-values by comparing our results with those from the CGEMS phase I data set. Seven tagSNPs had unadjusted p-values ≤ 0.05 in both our data and in CGEMS (two SNPs were identical and five were in strong linkage disequilibrium with CGEMS SNPs). These seven SNPs (rs17184211, rs4147684, rs4233367, rs2070902, rs3829037, rs7830235, and rs1203213) are located in genes MTRR, NDUFA9, NDUFS2, NDUFB9 and COX7A2, respectively. Five of the seven SNPs were further included in the CGEMS phase II study, however, none of the findings for these were replicated. Overall, these results suggest that polymorphisms in the mitochondrial genome and those in the nuclear encoded mitochondrial genes evaluated are not substantial risk factors for prostate cancer.