title: Mitochondrial genetic polymorphisms and pancreatic cancer risk.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street Southwest, Stabile 241, Rochester, MN 55905, USA. wang.liang@mayo.edu
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: William R
authors.initials: WR
authors.lastname: Bamlet
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Boardman
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Petersen
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D005819:Genetic Markers