Faculty Collaboration Database

Polymorphisms in mitochondrial genes and prostate cancer risk. Cancer Epidemiol Biomarkers Prev 2008 Dec;17(12):3558-66

Date

12/10/2008

Pubmed ID

19064571

Pubmed Central ID

PMC2750891

DOI

10.1158/1055-9965.EPI-08-0434

Scopus ID

2-s2.0-57449096146 (requires institutional sign-in at Scopus site)   45 Citations

Abstract

The mitochondrion, conventionally thought to be an organelle specific to energy metabolism, is in fact multifunctional 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 (SNP) within the mitochondrial genome and 376 tagSNPs localized to 78 nuclear-encoded mitochondrial genes. The tagSNPs were selected to achieve > or = 80% coverage based on linkage disequilibrium. We compared allele and haplotype frequencies in approximately 1,000 prostate cancer cases with approximately 500 population controls. An association with prostate cancer was not detected for any of the SNPs within the mitochondrial genome 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 Cancer Genetic Markers of Susceptibility (CGEMS) phase I data set. Seven tagSNPs had unadjusted P < or = 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.

Author List

Wang L, McDonnell SK, Hebbring SJ, Cunningham JM, St Sauver J, Cerhan JR, Isaya G, Schaid DJ, Thibodeau SN

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

Aged
Alleles
Case-Control Studies
Genes, Mitochondrial
Genetic Markers
Genetic Predisposition to Disease
Genotype
Haplotypes
Humans
Linkage Disequilibrium
Male
Middle Aged
Polymorphism, Single Nucleotide
Prostatic Neoplasms
Risk Factors