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North American White Mitochondrial Haplogroups in Prostate and Renal Cancer

2006; Lippincott Williams & Wilkins; Volume: 175; Issue: 2 Linguagem: Inglês

10.1016/s0022-5347(05)00163-1

1527-3792

Lyra M. Booker, Geoffrey M. Habermacher, Benjamin C. Jessie, Qi Carrie Sun, Amanda K. Baumann, Mohammed A. Amin, So Dug Lim, Carina Fernandez-Golarz, Robert H. Lyles, Michael D. Brown, Fray F. Marshall, John A. Petros,

Cancer, Hypoxia, and Metabolism

No AccessJournal of UrologyAdult urology1 Feb 2006North American White Mitochondrial Haplogroups in Prostate and Renal Cancer Lyra M. Booker, Geoffrey M. Habermacher, Benjamin C. Jessie, Qi Carrie Sun, Amanda K. Baumann, Mahul Amin, So Dug Lim, Carina Fernandez-Golarz, Robert H. Lyles, Michael D. Brown, Fray F. Marshall, and John A. Petros Lyra M. BookerLyra M. Booker Department of Urology, Macon, Georgia More articles by this author , Geoffrey M. HabermacherGeoffrey M. Habermacher Department of Urology, Macon, Georgia More articles by this author , Benjamin C. JessieBenjamin C. Jessie Department of Urology, Macon, Georgia More articles by this author , Qi Carrie SunQi Carrie Sun Department of Urology, Macon, Georgia More articles by this author , Amanda K. BaumannAmanda K. Baumann Department of Urology, Macon, Georgia More articles by this author , Mahul AminMahul Amin Department of Pathology and Laboratory Medicine, Macon, Georgia More articles by this author , So Dug LimSo Dug Lim Department of Pathology and Laboratory Medicine, Macon, Georgia More articles by this author , Carina Fernandez-GolarzCarina Fernandez-Golarz Department of Urology, Macon, Georgia More articles by this author , Robert H. LylesRobert H. Lyles School of Public Health, Macon, Georgia More articles by this author , Michael D. BrownMichael D. Brown Atlanta and Mercer University School of Medicine, Macon, Georgia More articles by this author , Fray F. MarshallFray F. Marshall Department of Urology, Macon, Georgia Financial interest and/or other relationship with Johnson & Johnson. More articles by this author , and John A. PetrosJohn A. Petros Department of Urology, Macon, Georgia Department of Pathology and Laboratory Medicine, Macon, Georgia Emory University and Atlanta Veterans Affairs Medical Center, Macon, Georgia More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)00163-1AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: While the mitochondrion is known to be a key mediator of apoptosis, there has been little inquiry into the inheritance pattern of mitochondria in patients with cancer. We compared the mtDNA haplotype in patients with prostate and renal cancer to that in controls to determine if there is an association between mitochondrial genotype and cancer. Materials and Methods: Haplotyping was performed using polymerase chain reaction/digest identification of key polymorphic sites in the mitochondrial genome. A total of 121 and 221 white men with renal and prostate cancer, respectively, were identified following pathological confirmation of cancer, while 246 white controls were selected randomly from a bank of cadaveric organ donor DNA. Statistical analysis was performed and ORs were calculated. Results: Mitochondrial haplogroup U was a highly significant risk factor for prostate and renal cancer vs controls (16.74% and 20.66% vs 9.35%, Fisher’s exact test p = 0.019 and 0.005, respectively). The association remained statistically significant in renal cancer even after Bonferroni adjustment for multiple comparisons. Haplogroup U carried an OR of 1.95 for prostate cancer and an OR of 2.52 for renal cancer. Conclusions: The inheritance of mitochondrial haplogroup U is associated with an approximately 2-fold increased risk of prostate cancer and 2.5-fold increased risk of renal cancer in white North American individuals. Therefore, individuals with this mitochondrial haplotype are in a high risk group. Because mitochondrial haplogroup U is found in 9.35% of the white United States population, there are more than 20 million individuals in this high risk group. References 1 Cancer Facts and Figures 2005.. Atlanta: American Cancer Society2005. Google Scholar 2 : On the origin of cancer cells. Science1956; 123: 309. Crossref, Medline, Google Scholar 3 : Vanadate-induced expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor through phosphatidylinositol 3-kinase/Akt pathway and reactive oxygen species. J Biol Chem2002; 277: 31963. Google Scholar 4 : Mitochondria and neuro-opthalmologic diseases. In: The Metabolic and Molecular Bases of Inherited Disease. Edited by . New York: McGraw-Hill2001: 2425. Google Scholar 5 : Large scale screening of the mitochondrial DNA reveals no pathogenic mutations but a haplotype associated with multiple sclerosis in Caucasians. Acta Neurol Scand1999; 99: 16. Google Scholar 6 : Classification of European mtDNAs from an analysis of three European populations. Genetics1996; 144: 1835. Google Scholar 7 : Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans. FASEB J1999; 13: 1532. Google Scholar 8 : Human mtDNA haplogroups associated with high or reduced spermatozoa motility. Am J Hum Genet2000; 67: 682. Google Scholar 9 : Mitochondrial DNA mutations in multiple sclerosis. Mult Scler1995; 1: 32. Google Scholar 10 : Wolfram (DIDMOAD) syndrome and Leber hereditary optic neuropathy (LHON) are associated with distinct mitochondrial DNA haplotypes. Genomics1997; 39: 8. Google Scholar 11 : Mitochondrial DNA haplogroup U as a risk factor for occipital stroke in migraine. Lancet1998; 352: 455. Google Scholar 12 : Mitochondrial mutation as a probable causative factor in familial progressive tubulointerstitial nephritis. Hum Genet1997; 99: 484. Google Scholar 13 : Paleolithic and neolithic lineages in the European mitochondrial gene pool. Am J Hum Genet1996; 59: 185. Google Scholar 14 : Risk of genitourinary malignancies after cancer of the prostate. Cancer1988; 61: 396. Google Scholar 15 : Second primary cancers following cancers of the kidney and prostate in New South Wales (Australia), 1972-91. Cancer Causes Control1996; 7: 337. Google Scholar 16 : Second primary malignancies in T1-3N0 prostate cancer patients treated with radiation therapy with 10-year followup. J Urol1998; 159: 946. Link, Google Scholar 17 : Second primary malignancies associated with renal cell carcinoma influence of histologic type. Urology2000; 56: 399. Google Scholar 18 : Cancer risk in families with hereditary prostate carcinoma. Cancer2000; 89: 1315. Google Scholar 19 : Familial risk of prostate cancer in Iceland. BJU Int2003; 92: 915. Google Scholar © 2006 by American Urological AssociationFiguresReferencesRelatedDetailsCited byMarshall F (2009) Urological Oncology: Renal, Ureteral and Retroperitoneal TumorsJournal of Urology, VOL. 182, NO. 1, (94-95), Online publication date: 1-Jul-2009. Volume 175Issue 2February 2006Page: 468-473 Advertisement Copyright & Permissions© 2006 by American Urological AssociationKeywordsDNA, mitochondrialriskrenal neoplasmsEuropean continental ancestry groupprostatic neoplasmsAcknowledgmentsC. R. Robinson provided specimens from patients with cancer, Keith Kerstann provided technical advice and support, and Kim Kerstann performed the statistical analysis. Controls were provided by the Histocompatibility and Molecular Immunogenetics Laboratory, Emory University Hospital.Metrics Author Information Lyra M. Booker Department of Urology, Macon, Georgia More articles by this author Geoffrey M. Habermacher Department of Urology, Macon, Georgia More articles by this author Benjamin C. Jessie Department of Urology, Macon, Georgia More articles by this author Qi Carrie Sun Department of Urology, Macon, Georgia More articles by this author Amanda K. Baumann Department of Urology, Macon, Georgia More articles by this author Mahul Amin Department of Pathology and Laboratory Medicine, Macon, Georgia More articles by this author So Dug Lim Department of Pathology and Laboratory Medicine, Macon, Georgia More articles by this author Carina Fernandez-Golarz Department of Urology, Macon, Georgia More articles by this author Robert H. Lyles School of Public Health, Macon, Georgia More articles by this author Michael D. Brown Atlanta and Mercer University School of Medicine, Macon, Georgia More articles by this author Fray F. Marshall Department of Urology, Macon, Georgia Financial interest and/or other relationship with Johnson & Johnson. More articles by this author John A. Petros Department of Urology, Macon, Georgia Department of Pathology and Laboratory Medicine, Macon, Georgia Emory University and Atlanta Veterans Affairs Medical Center, Macon, Georgia More articles by this author Expand All Advertisement PDF downloadLoading ...