Wang Liang, Bamlet William R, de Andrade Mariza, Boardman Lisa A, Cunningham Julie M, Thibodeau Stephen N, Petersen Gloria M
Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street Southwest, Stabile 241, Rochester, MN 55905, USA.
Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1455-9. doi: 10.1158/1055-9965.EPI-07-0119.
The role of genes that influence the risk of developing pancreatic cancer (PC) has not been well studied. The mitochondrion, conventionally thought to be an organelle specific to energy metabolism, is in fact multifunctional and has been implicated in many diseases, including cancer. To evaluate whether single nucleotide polymorphisms in mitochondrial DNA (mtSNP) are associated with increased risk of PC, we screened Caucasian cases diagnosed or seen at the Mayo Clinic with primary pancreatic adenocarcinoma (n = 955), and healthy clinic-based Caucasian controls (n = 1,102). A total of 24 mtSNPs, including 10 of the most common tagSNPs, 7 non-tagSNPs in the coding region, and 7 common SNPs in the regulatory region were genotyped. For analysis, these samples were grouped into two phases, the "testing" set (474 cases and 615 controls), and the "validation" set (481 cases and 487 controls). In the testing set, one mtSNP (SNP11719) suggested an association in single SNP analysis, with an odds ratio of 1.34 (95% confidence intervals, 1.05-1.72; P = 0.020), but did not remain statistically significant after correction for multiple testing. In the validation set, none of the 24 variants indicated any association with PC. For haplogroup analysis, 10 core SNPs that form common haplogroups in Caucasians (1719, 4580, 7028, 8251, 9055, 10398, 12308, 13368, 13708, and 16391) were evaluated. No significant associations with PC were identified either by analyzing the two sets separately or combined (combined global P = 0.17). Overall, these results do not support a significant involvement of mitochondrial DNA variation in the risk of developing PC. Investigation of other mitochondrial genetic variations (i.e., nuclear-encoded mitochondrial proteins) would be necessary to elucidate any role of mitochondrial DNA variation in PC.
影响胰腺癌（PC）发病风险的基因作用尚未得到充分研究。线粒体，传统上被认为是一种专门负责能量代谢的细胞器，实际上具有多种功能，并且与包括癌症在内的许多疾病都有关联。为了评估线粒体DNA单核苷酸多态性（mtSNP）是否与PC发病风险增加相关，我们对在梅奥诊所诊断或就诊的原发性胰腺腺癌的白种人病例（n = 955）以及以诊所为基础的健康白种人对照（n = 1,102）进行了筛查。总共对24个mtSNP进行了基因分型，其中包括10个最常见的标签SNP、7个编码区域的非标签SNP以及7个调控区域的常见SNP。为了进行分析，这些样本被分为两个阶段，即“测试”组（474例病例和615例对照）和“验证”组（481例病例和487例对照）。在测试组中，一个mtSNP（SNP11719）在单SNP分析中显示出关联，优势比为1.34（95%置信区间，1.05 - 1.72；P = 0.020），但在多重检验校正后不再具有统计学显著性。在验证组中，24个变体均未显示与PC有任何关联。对于单倍群分析，评估了在白种人中形成常见单倍群的10个核心SNP（1719、4580、7028、8251、9055、10398、12308、13368、13708和16391）。无论是分别分析这两组还是将它们合并分析（合并总体P = 0.17），均未发现与PC有显著关联。总体而言，这些结果不支持线粒体DNA变异在PC发病风险中起重要作用。有必要研究其他线粒体遗传变异（即核编码的线粒体蛋白），以阐明线粒体DNA变异在PC中的任何作用。
