Mitochondrial Haplogroups and Control Region Polymorphisms Are Not Associated with Prostate Cancer in Middle European Caucasians

Background Besides being responsible for energy production in the cell, mitochondria are central players in apoptosis as well as the main source of harmful reactive oxygen species. Therefore, it can be hypothesised that sequence variation in the mitochondrial genome is a contributing factor to the etiology of diseases related to these different cellular events, including cancer. The aim of the present study was to assess the frequency of haplogroups and polymorphisms in the control region (CR) of mitochondrial DNA of peripheral blood mononuclear cells from patients with prostate carcinoma (n = 304) versus patients screened for prostate disease but found to be negative for cancer on biopsy (n = 278) in a Middle European population. Methodology/Principal Findings The nine major European haplogroups and the CR polymorphisms were identified by means of primer extension analysis and DNA sequencing, respectively. We found that mitochondrial haplogroup frequencies and CR polymorphisms do not differ significantly between patients with or without prostate cancer, implying no impact of inherited mitochondrial DNA variation on predisposition to prostate carcinoma in a Middle European population. Conclusions/Significance Our results contrast with a recent report claiming an association between mtDNA haplogroup U and prostate cancer in a North American population of caucasian descent.

[1]  B. Paulweber,et al.  Mitochondrial DNA haplogroup T is associated with coronary artery disease and diabetic retinopathy: a case control study , 2009, BMC Medical Genetics.

[2]  E. Condom,et al.  The Prostate 68 : 1086 ^ 1096 ( 2008 ) Altered Expressionof 12 S / MT-RNR 1 , MT-CO 2 / COX 2 , and MT-ATP 6 MitochondrialGenes in ProstateCancer , 2008 .

[3]  Dong-jik Shin,et al.  Mitochondrial DNA Haplogroup Analysis Reveals no Association between the Common Genetic Lineages and Prostate Cancer in the Korean Population , 2008, PloS one.

[4]  H. Klocker,et al.  Tyrol Prostate Cancer Demonstration Project: early detection, treatment, outcome, incidence and mortality , 2008, BJU international.

[5]  A. Jemal,et al.  Cancer Statistics, 2008 , 2008, CA: a cancer journal for clinicians.

[6]  S. Leal,et al.  Mitochondrial genetic background modifies breast cancer risk. , 2007, Cancer research.

[7]  K. Darvishi,et al.  Mitochondrial DNA G10398A polymorphism imparts maternal Haplogroup N a risk for breast and esophageal cancer. , 2007, Cancer letters.

[8]  A. Kallianpur,et al.  Re: North American white mitochondrial haplogroups in prostate and renal cancer. , 2006, The Journal of urology.

[9]  B. Paulweber,et al.  Multiplex primer extension analysis for rapid detection of major European mitochondrial haplogroups , 2006, Electrophoresis.

[10]  H. Klocker,et al.  Reduction of prostate cancer mortality in Tyrol, Austria, after introduction of prostate-specific antigen testing. , 2006, American journal of epidemiology.

[11]  P. Chinnery,et al.  The power to detect disease associations with mitochondrial DNA haplogroups. , 2006, American journal of human genetics.

[12]  E. Condom,et al.  Identification of somatic and germline mitochondrial DNA sequence variants in prostate cancer patients. , 2006, Mutation research.

[13]  Laura C. Greaves,et al.  Mitochondrial DNA mutations in human disease , 2006, IUBMB life.

[14]  F. Marshall,et al.  North American white mitochondrial haplogroups in prostate and renal cancer. , 2006, The Journal of urology.

[15]  W. Tang,et al.  Mitochondrial polymorphisms as risk factors for endometrial cancer in southwest China , 2006, International Journal of Gynecologic Cancer.

[16]  R. Millikan,et al.  Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. , 2005, Cancer research.

[17]  A. Amorim,et al.  Human mtDNA haplogroups and reduced male fertility: real association or hidden population substructuring. , 2005, International journal of andrology.

[18]  Michael C Whitlock,et al.  The incomplete natural history of mitochondria , 2004, Molecular ecology.

[19]  P. Murail,et al.  mtDNA polymorphisms in five French groups: importance of regional sampling , 2004, European Journal of Human Genetics.

[20]  T. Parsons,et al.  Rapid screening of mtDNA coding region SNPs for the identification of west European Caucasian haplogroups , 2003, International Journal of Legal Medicine.

[21]  Junjian Z. Chen,et al.  Extensive somatic mitochondrial mutations in primary prostate cancer using laser capture microdissection. , 2002, Cancer research.

[22]  J. T. Wachsman,et al.  Mitochondrial DNA in human malignancy. , 2001, Mutation research.

[23]  D. Wallace,et al.  Mitochondrial DNA variation in human evolution and disease. , 1999, Gene.

[24]  J. Taanman,et al.  The mitochondrial genome: structure, transcription, translation and replication. , 1999, Biochimica et biophysica acta.

[25]  D. Wallace,et al.  Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage. , 1997, American journal of human genetics.

[26]  A. Torroni,et al.  Classification of European mtDNAs from an analysis of three European populations. , 1996, Genetics.

[27]  A. Torroni,et al.  mtDNA and the origin of Caucasians: identification of ancient Caucasian-specific haplogroups, one of which is prone to a recurrent somatic duplication in the D-loop region. , 1994, American journal of human genetics.

[28]  A. Torroni,et al.  Mitochondrial DNA variation in human populations and implications for detection of mitochondrial DNA mutations of pathological significance , 1994, Journal of bioenergetics and biomembranes.

[29]  O. Warburg.  [Origin of cancer cells]. , 1956, Oncologia.

[30]  A. Torroni,et al.  Phylogenetic analysis of Leber's hereditary optic neuropathy mitochondrial DNA's indicates multiple independent occurrences of the common mutations , 1995, Human mutation.

[31]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.