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

Edith E Mueller,Wolfgang Sperl,Waltraud Eder,Helmut Klocker,Wolfgang Horninger,Johannes A Mayr,Bernhard Paulweber,Barbara Kofler,Andrew Vickers

doi:10.1371/journal.pone.0006370

Edith E Mueller, Wolfgang Sperl + Show 7 more

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https://doi.org/10.1371/journal.pone.0006370

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Abstract

BackgroundBesides 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 FindingsThe 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/SignificanceOur results contrast with a recent report claiming an association between mtDNA haplogroup U and prostate cancer in a North American population of caucasian descent.

Highlights

Prostate cancer is a major cause of death in the developed world
We assessed the nine major European haplogroups as well as control region (CR) polymorphisms in peripheral blood mononuclear cells of 582 Caucasian males, 304 of whom were diagnosed with prostate cancer; the remaining 278 were identified with elevated serum PSA levels but were histologically negative for cancer upon prostate biopsy and served as the control group
When mitochondrial haplogroup frequencies were compared between cancer patients with biopsy Gleason Score #6 to cancer patients with biopsy Gleason Score $7 no significant differences were observed (Table 3)

Summary

Introduction

Prostate cancer is a major cause of death in the developed world. It is the most frequent cancer among men in the United States and the second most common in the European Union [1,2].A shift in cellular energy production from oxidative phosphorylation in mitochondria to anaerobic glycolysis, called the Warburg effect, is a fundamental property of cancer cells. Prostate cancer is a major cause of death in the developed world. It is the most frequent cancer among men in the United States and the second most common in the European Union [1,2]. A shift in cellular energy production from oxidative phosphorylation in mitochondria to anaerobic glycolysis, called the Warburg effect, is a fundamental property of cancer cells. Mitochondrial respiratory activity is associated with the generation of reactive oxygen species (ROS), which may contribute to the etiology and progression of cancer [4]. 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.

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