Faculty Collaboration Database

Mitochondrial genetic polymorphisms and pancreatic cancer risk. Cancer Epidemiol Biomarkers Prev 2007 Jul;16(7):1455-9

Date

07/14/2007

Pubmed ID

17627010

DOI

10.1158/1055-9965.EPI-07-0119

Scopus ID

2-s2.0-34447498590 (requires institutional sign-in at Scopus site)   74 Citations

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.

Author List

Wang L, Bamlet WR, de Andrade M, Boardman LA, Cunningham JM, Thibodeau SN, Petersen GM

MESH terms used to index this publication - Major topics in bold

Aged
Case-Control Studies
DNA, Mitochondrial
Female
Gene Frequency
Genetic Markers
Genetic Predisposition to Disease
Genetic Variation
Genotype
Humans
Male
Middle Aged
Mitochondria
Pancreatic Neoplasms
Polymorphism, Single Nucleotide
Risk Factors