<> "The repository administrator has not yet configured an RDF license."^^ . <> . . . "An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers"^^ . "Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects. "^^ . "2015" . . "17" . "61" . . "BioMed Central"^^ . . . "Breast Cancer Research"^^ . . . "1465542X" . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . "Georgia"^^ . "Chenevix-Trench"^^ . "Georgia Chenevix-Trench"^^ . . "Lisa"^^ . "Walker"^^ . "Lisa Walker"^^ . . "Ans MW"^^ . "van den Ouweland"^^ . "Ans MW van den Ouweland"^^ . . "William"^^ . "Foulkes"^^ . "William Foulkes"^^ . . "Robert L."^^ . "Nussbaum"^^ . "Robert L. Nussbaum"^^ . . "Alex"^^ . "Teulé"^^ . "Alex Teulé"^^ . . "Sylvie"^^ . "Mazoyer"^^ . "Sylvie Mazoyer"^^ . . "Norbert"^^ . "Arnold"^^ . "Norbert Arnold"^^ . . "Kristiina"^^ . "Aittomäki"^^ . "Kristiina Aittomäki"^^ . . "Katherine L."^^ . "Nathanson"^^ . "Katherine L. Nathanson"^^ . . "Jesús"^^ . "Del Valle"^^ . "Jesús Del Valle"^^ . . "Grzegorz"^^ . "Sukiennicki"^^ . "Grzegorz Sukiennicki"^^ . . "Laure"^^ . "Barjhoux"^^ . "Laure Barjhoux"^^ . . "Jonathan"^^ . "Carter"^^ . "Jonathan Carter"^^ . . "Linda"^^ . "Van Le"^^ . "Linda Van Le"^^ . . "Gillian"^^ . "Mitchell"^^ . "Gillian Mitchell"^^ . . "Maria A."^^ . "Caligo"^^ . "Maria A. Caligo"^^ . . "Nadja B."^^ . "Markov"^^ . "Nadja B. Markov"^^ . . "Laura"^^ . "Ottini"^^ . "Laura Ottini"^^ . . "Nadine"^^ . "Tung"^^ . "Nadine Tung"^^ . . "Barbara"^^ . "Wappenschmidt"^^ . "Barbara Wappenschmidt"^^ . . "Andrea"^^ . "Gehrig"^^ . "Andrea Gehrig"^^ . . "Sandra"^^ . "Orsulic"^^ . "Sandra Orsulic"^^ . . "David G."^^ . "Cox"^^ . "David G. Cox"^^ . . "Yael"^^ . "Laitman"^^ . "Yael Laitman"^^ . . "Karin"^^ . "Kast"^^ . "Karin Kast"^^ . . "Cora M."^^ . "Aalfs"^^ . "Cora M. Aalfs"^^ . . "Fiona"^^ . "Douglas"^^ . "Fiona Douglas"^^ . . "Rob B."^^ . "van der Luijt"^^ . "Rob B. van der Luijt"^^ . . "Gord"^^ . "Glendon"^^ . "Gord Glendon"^^ . . "Susan J."^^ . "Ramus"^^ . "Susan J. Ramus"^^ . . "Laima"^^ . "Tihomirova"^^ . "Laima Tihomirova"^^ . . "Ramunas"^^ . "Janavicius"^^ . "Ramunas Janavicius"^^ . . "Sophie"^^ . "Blein"^^ . "Sophie Blein"^^ . . "Raquel Andrés"^^ . "Conejero"^^ . "Raquel Andrés Conejero"^^ . . "Giulietta"^^ . "Scuvera"^^ . "Giulietta Scuvera"^^ . . "Louise"^^ . "Izatt"^^ . "Louise Izatt"^^ . . "Anne"^^ . "Lincoln"^^ . "Anne Lincoln"^^ . . "Jackie"^^ . "Cook"^^ . "Jackie Cook"^^ . . "Drakoulis"^^ . "Yannoukakos"^^ . "Drakoulis Yannoukakos"^^ . . "M John"^^ . "Kennedy"^^ . "M John Kennedy"^^ . . "Shan"^^ . "Wang-Gohrke"^^ . "Shan Wang-Gohrke"^^ . . "Doris"^^ . "Steinemann"^^ . "Doris Steinemann"^^ . . "Jeffrey N."^^ . "Weitzel"^^ . "Jeffrey N. Weitzel"^^ . . "Kim"^^ . "De Leeneer"^^ . "Kim De Leeneer"^^ . . "Alberto"^^ . "Amadori"^^ . "Alberto Amadori"^^ . . "Penny"^^ . "Soucy"^^ . "Penny Soucy"^^ . . "Banu K."^^ . "Arun"^^ . "Banu K. Arun"^^ . . "Nancy"^^ . "Uhrhammer"^^ . "Nancy Uhrhammer"^^ . . "Timothy R."^^ . "Rebbeck"^^ . "Timothy R. Rebbeck"^^ . . "Elizabeth J."^^ . "van Rensburg"^^ . "Elizabeth J. van Rensburg"^^ . . "Finn C."^^ . "Nielsen"^^ . "Finn C. Nielsen"^^ . . "Mary B."^^ . "Terry"^^ . "Mary B. Terry"^^ . . "Judy"^^ . "Garber"^^ . "Judy Garber"^^ . . "Mark H."^^ . "Greene"^^ . "Mark H. Greene"^^ . . "Etienne"^^ . "Rouleau"^^ . "Etienne Rouleau"^^ . . "Beatrice"^^ . "Melin"^^ . "Beatrice Melin"^^ . . "Amanda"^^ . "Ewart Toland"^^ . "Amanda Ewart Toland"^^ . . "Margo"^^ . "Thelander"^^ . "Margo Thelander"^^ . . "Karoline B."^^ . "Kuchenbaecker"^^ . "Karoline B. Kuchenbaecker"^^ . . "Javier"^^ . "Benitez"^^ . "Javier Benitez"^^ . . "Daniel"^^ . "Barrowdale"^^ . "Daniel Barrowdale"^^ . . "Valeria"^^ . "Pensotti"^^ . "Valeria Pensotti"^^ . . "Olga M."^^ . "Sinilnikova"^^ . "Olga M. Sinilnikova"^^ . . "Uffe Birk"^^ . "Jensen"^^ . "Uffe Birk Jensen"^^ . . "Christine"^^ . "Lasset"^^ . "Christine Lasset"^^ . . "Lesley"^^ . "McGuffog"^^ . "Lesley McGuffog"^^ . . "Jacek"^^ . "Gronwald"^^ . "Jacek Gronwald"^^ . . "Daniela"^^ . "Zaffaroni"^^ . "Daniela Zaffaroni"^^ . . "Mads"^^ . "Thomassen"^^ . "Mads Thomassen"^^ . . "Conxi"^^ . "Lazaro"^^ . "Conxi Lazaro"^^ . . "Torben A."^^ . "Kruse"^^ . "Torben A. Kruse"^^ . . "Alfons"^^ . "Meindl"^^ . "Alfons Meindl"^^ . . "Lucy E."^^ . "Side"^^ . "Lucy E. Side"^^ . . "Julian"^^ . "Barwell"^^ . "Julian Barwell"^^ . . "Curtis"^^ . "Olswold"^^ . "Curtis Olswold"^^ . . "Christian F."^^ . "Singer"^^ . "Christian F. Singer"^^ . . "Jan C."^^ . "Oosterwijk"^^ . "Jan C. Oosterwijk"^^ . . "Paolo"^^ . "Radice"^^ . "Paolo Radice"^^ . . "Flora E."^^ . "van Leeuwen"^^ . "Flora E. van Leeuwen"^^ . . "Lisa"^^ . "Golmard"^^ . "Lisa Golmard"^^ . . "Cecilia M."^^ . "Dorfling"^^ . "Cecilia M. Dorfling"^^ . . "Trevor"^^ . "Cole"^^ . "Trevor Cole"^^ . . "Christoph"^^ . "Engel"^^ . "Christoph Engel"^^ . . "Olufunmilayo I."^^ . "Olopade"^^ . "Olufunmilayo I. Olopade"^^ . . "Anna"^^ . "Jakubowska"^^ . "Anna Jakubowska"^^ . . "Wendy K."^^ . "Chung"^^ . "Wendy K. Chung"^^ . . "Paolo"^^ . "Peterlongo"^^ . "Paolo Peterlongo"^^ . . "Andrew"^^ . "Lee"^^ . "Andrew Lee"^^ . . "Ena"^^ . "Segota"^^ . "Ena Segota"^^ . . "Sabine"^^ . "Preisler-Adams"^^ . "Sabine Preisler-Adams"^^ . . "D. Gareth"^^ . "Evans"^^ . "D. Gareth Evans"^^ . . "Bernard"^^ . "Peissel"^^ . "Bernard Peissel"^^ . . "Joe"^^ . "Dennis"^^ . "Joe Dennis"^^ . . "Valérie"^^ . "Bonadona"^^ . "Valérie Bonadona"^^ . . "Trinidad"^^ . "Caldes"^^ . "Trinidad Caldes"^^ . . "Ana"^^ . "Osorio"^^ . "Ana Osorio"^^ . . "Andreas"^^ . "Berger"^^ . "Andreas Berger"^^ . . "Angela"^^ . "Brady"^^ . "Angela Brady"^^ . . "Amanda B."^^ . "Spurdle"^^ . "Amanda B. Spurdle"^^ . . "Manuel R."^^ . "Teixeira"^^ . "Manuel R. Teixeira"^^ . . "Jacques"^^ . "Simard"^^ . "Jacques Simard"^^ . . "Orland"^^ . "Diez"^^ . "Orland Diez"^^ . . "Cédrick"^^ . "Lefol"^^ . "Cédrick Lefol"^^ . . "Patrick J"^^ . "Morrison"^^ . "Patrick J Morrison"^^ . . "Edith"^^ . "Olah"^^ . "Edith Olah"^^ . . "Kathleen"^^ . "Claes"^^ . "Kathleen Claes"^^ . . "Jamal"^^ . "Zidan"^^ . "Jamal Zidan"^^ . . "Mark"^^ . "Robson"^^ . "Mark Robson"^^ . . "Noralane M."^^ . "Lindor"^^ . "Noralane M. Lindor"^^ . . "Nina"^^ . "Ditsch"^^ . "Nina Ditsch"^^ . . "Anneliese"^^ . "Fink-Retter"^^ . "Anneliese Fink-Retter"^^ . . "Dominique"^^ . "Stoppa-Lyonnet"^^ . "Dominique Stoppa-Lyonnet"^^ . . "Claudine"^^ . "Isaacs"^^ . "Claudine Isaacs"^^ . . "Sue"^^ . "Healey"^^ . "Sue Healey"^^ . . "Evgeny N."^^ . "Imyanitov"^^ . "Evgeny N. Imyanitov"^^ . . "Vernon S."^^ . "Pankratz"^^ . "Vernon S. Pankratz"^^ . . "Lauren"^^ . "Jacobs"^^ . "Lauren Jacobs"^^ . . "Anne-Marie"^^ . "Gerdes"^^ . "Anne-Marie Gerdes"^^ . . "Fergus J."^^ . "Couch"^^ . "Fergus J. Couch"^^ . . "Susan L."^^ . "Neuhausen"^^ . "Susan L. Neuhausen"^^ . . "Mary E"^^ . "Porteous"^^ . "Mary E Porteous"^^ . . "Christine"^^ . "Maugard"^^ . "Christine Maugard"^^ . . "David E."^^ . "Goldgar"^^ . "David E. Goldgar"^^ . . "Catherine M."^^ . "Phelan"^^ . "Catherine M. Phelan"^^ . . "Carole"^^ . "Brewer"^^ . "Carole Brewer"^^ . . "Carolien M."^^ . "Kets"^^ . "Carolien M. Kets"^^ . . "Vincent"^^ . "Danjean"^^ . "Vincent Danjean"^^ . . "Liliana"^^ . "Varesco"^^ . "Liliana Varesco"^^ . . "Katarzyna"^^ . "Jaworska-Bieniek"^^ . "Katarzyna Jaworska-Bieniek"^^ . . "Riccardo"^^ . "Dolcetti"^^ . "Riccardo Dolcetti"^^ . . "Debra"^^ . "Frost"^^ . "Debra Frost"^^ . . "Dieter"^^ . "Niederacher"^^ . "Dieter Niederacher"^^ . . "Hanne EJ"^^ . " Meijers-Heijboer"^^ . "Hanne EJ Meijers-Heijboer"^^ . . "Antoine"^^ . "de Pauw"^^ . "Antoine de Pauw"^^ . . "Katarzyna"^^ . "Durda"^^ . "Katarzyna Durda"^^ . . "Frans BL"^^ . "Hogervorst"^^ . "Frans BL Hogervorst"^^ . . "Christine"^^ . "Rappaport"^^ . "Christine Rappaport"^^ . . "Csilla I."^^ . "Szabo"^^ . "Csilla I. Szabo"^^ . . "Yuan Chun"^^ . "Ding"^^ . "Yuan Chun Ding"^^ . . "Gabriele L."^^ . "Capone"^^ . "Gabriele L. Capone"^^ . . "Annika"^^ . "Lindblom"^^ . "Annika Lindblom"^^ . . "Beth Y."^^ . "Karlan"^^ . "Beth Y. Karlan"^^ . . "Ignacio"^^ . "Blanco"^^ . "Ignacio Blanco"^^ . . "Rosemarie"^^ . "Davidson"^^ . "Rosemarie Davidson"^^ . . "Matti A."^^ . "Rookus"^^ . "Matti A. Rookus"^^ . . "Claire"^^ . "Bardel"^^ . "Claire Bardel"^^ . . "Peter"^^ . "Devilee"^^ . "Peter Devilee"^^ . . "Brita"^^ . "Arver"^^ . "Brita Arver"^^ . . "Eitan"^^ . "Friedman"^^ . "Eitan Friedman"^^ . . "Hansjörg"^^ . "Plendl"^^ . "Hansjörg Plendl"^^ . . "Irene L"^^ . "Andrulis"^^ . "Irene L Andrulis"^^ . . "Bernardo"^^ . "Bonanni"^^ . "Bernardo Bonanni"^^ . . "Ute"^^ . "Hamann"^^ . "Ute Hamann"^^ . . "Jenny"^^ . "Lester"^^ . "Jenny Lester"^^ . . "Marion"^^ . "Piedmonte"^^ . "Marion Piedmonte"^^ . . "Richard"^^ . "Rosenquist"^^ . "Richard Rosenquist"^^ . . "Yves-Jean"^^ . "Bignon"^^ . "Yves-Jean Bignon"^^ . . "Marc"^^ . "Tischkowitz"^^ . "Marc Tischkowitz"^^ . . "Thomas VO"^^ . "Hansen"^^ . "Thomas VO Hansen"^^ . . "Miguel"^^ . "de la Hoya"^^ . "Miguel de la Hoya"^^ . . "Georg"^^ . "Pfeiler"^^ . "Georg Pfeiler"^^ . . "Bent"^^ . "Ejlertsen"^^ . "Bent Ejlertsen"^^ . . "Christian"^^ . "Sutter"^^ . "Christian Sutter"^^ . . "Marco"^^ . "Montagna"^^ . "Marco Montagna"^^ . . "Agnes"^^ . "Jager"^^ . "Agnes Jager"^^ . . "Anna Marie"^^ . "Mulligan"^^ . "Anna Marie Mulligan"^^ . . "Phuong L."^^ . "Mai"^^ . "Phuong L. Mai"^^ . . "Rita K."^^ . "Schmutzler"^^ . "Rita K. Schmutzler"^^ . . "Heli"^^ . "Nevanlinna"^^ . "Heli Nevanlinna"^^ . . "Shirley"^^ . "Hodgson"^^ . "Shirley Hodgson"^^ . . "Ros"^^ . "Eeles"^^ . "Ros Eeles"^^ . . "Muy-Kheng"^^ . "Tea"^^ . "Muy-Kheng Tea"^^ . . "Gilles"^^ . "Thomas"^^ . "Gilles Thomas"^^ . . "Julian"^^ . "Adlard"^^ . "Julian Adlard"^^ . . "Jan"^^ . "Lubinski"^^ . "Jan Lubinski"^^ . . "Kees EP"^^ . "van Roozendaal"^^ . "Kees EP van Roozendaal"^^ . . "Laura"^^ . "Papi"^^ . "Laura Papi"^^ . . "Claire"^^ . "Foo"^^ . "Claire Foo"^^ . . "Siranoush"^^ . "Manoukian"^^ . "Siranoush Manoukian"^^ . . "Irene"^^ . "Konstantopoulou"^^ . "Irene Konstantopoulou"^^ . . "Andrew K"^^ . "Godwin"^^ . "Andrew K Godwin"^^ . . "Niklas"^^ . "Loman"^^ . "Niklas Loman"^^ . . "Susan M."^^ . "Domchek"^^ . "Susan M. Domchek"^^ . . "Antonis C."^^ . "Antoniou"^^ . "Antonis C. Antoniou"^^ . . "Saundra S."^^ . "Buys"^^ . "Saundra S. Buys"^^ . . "Raymonda"^^ . "Varon-Mateeva"^^ . "Raymonda Varon-Mateeva"^^ . . "Douglas F."^^ . "Easton"^^ . "Douglas F. Easton"^^ . . "Sandrine"^^ . "Tchatchou"^^ . "Sandrine Tchatchou"^^ . . "Marina"^^ . "Corines"^^ . "Marina Corines"^^ . . "Valérie"^^ . "Sornin"^^ . "Valérie Sornin"^^ . . "Joseph"^^ . "Vijai"^^ . "Joseph Vijai"^^ . . "Alan"^^ . "Donaldson"^^ . "Alan Donaldson"^^ . . "Inge"^^ . "Sokilde Pedersen"^^ . "Inge Sokilde Pedersen"^^ . . "Dominique"^^ . "Leroux"^^ . "Dominique Leroux"^^ . . "Daphne"^^ . "Geschwantler Kaulich"^^ . "Daphne Geschwantler Kaulich"^^ . . "Paul A."^^ . "DiSilvestro"^^ . "Paul A. DiSilvestro"^^ . . "Francesca"^^ . "Damiola"^^ . "Francesca Damiola"^^ . . "Kerstin"^^ . "Rhiem"^^ . "Kerstin Rhiem"^^ . . "Radka"^^ . "Platte"^^ . "Radka Platte"^^ . . "Mark T"^^ . "Rogers"^^ . "Mark T Rogers"^^ . . "Gad"^^ . "Rennert"^^ . "Gad Rennert"^^ . . "Kenneth"^^ . "Offit"^^ . "Kenneth Offit"^^ . . "Diana"^^ . "Eccles"^^ . "Diana Eccles"^^ . . "Bjarni A."^^ . "Agnarsson"^^ . "Bjarni A. Agnarsson"^^ . . "Hélène"^^ . "Dreyfus"^^ . "Hélène Dreyfus"^^ . . . . . . "An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers (PDF)"^^ . . . "13058_2015_Article_567.pdf"^^ . . . "An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers (Other)"^^ . . . . . . "preview.jpg"^^ . . . "An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers (Other)"^^ . . . . . . "medium.jpg"^^ . . . "An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #19471 \n\nAn original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers\n\n" . "text/html" . . . "610 Medizin"@de . "610 Medical sciences Medicine"@en . .