The University of Southampton
University of Southampton Institutional Repository

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers
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.
1-15
Blein, Sophie
4194da3c-87b1-4fa5-8fa5-89f4dc05ee78
Bardel, Claire
1f85d56e-1fd8-47fb-b8d2-f25163b52041
Danjean, Vincent
61ea72c4-de51-423a-96d9-30afef7dfe5b
McGuffog, Lesley
21522096-38bb-45df-aa56-caf2f27d7254
Healey, Sue
5d595192-5381-464d-85cc-71ad09a05065
Barrowdale, Daniel
507bc817-9e80-4ff2-a379-470e0d6ed2c9
Lee, Andrew
a82db836-29cd-4bf5-a96a-fb6af545b310
Dennis, Joe
bd305c84-d968-4946-b154-a5bedb469210
Kuchenbaecker, Karoline B.
c72c2a25-9297-47bc-a4c0-f6e135ed0854
Soucy, Penny
c8606457-7865-44a4-90ce-de2b55994738
Terry, Mary Beth
f4e42578-34d7-4e36-a71d-2c174d62b9c3
Chung, Wendy K.
c7c336a6-b597-432b-b8df-abd1a2d3de14
Goldgar, David E.
102af7b6-41ab-46c0-9d76-43359c897e2e
Buys, Saundra S.
5b1a7cea-6562-4fb0-b2a9-06b08d5e86e6
Janavicius, Ramunas
314ff9ed-91c2-49cc-aa80-5ab072225a98
Tihomirova, Laima
b3d01d1c-8064-4610-ab37-0b9c169a027c
Tung, Nadine
9a999423-a6aa-41a5-957f-2d788ee3da15
Dorfling, Cecilia M.
e277a79f-0fec-4028-9408-5b8624ea05c6
van Rensburg, Elizabeth J.
d4dd3b97-d9ee-4968-97f4-4e8aa97c574a
Neuhausen, Susan L.
7cb359d3-5964-460c-ad60-63b77368c042
Ding, Yuan Chun
107aa0a1-2546-46b0-a1e5-a9d6dcb26744
Gerdes, Anne-Marie
60e03234-c7bd-4659-a642-432c0f943474
Ejlertsen, Bent
b9f56a71-7d7c-4a1d-98d2-fdd32e7a3ad7
Nielsen, Finn C
e3773c0a-25a2-4cc2-8120-3d7de8394da3
Hansen, Thomas VO
f679b4a0-4065-470a-83ca-3f4efee13213
Osorio, Ana
5d37d9d7-d889-4e14-ad7c-7b7f73f6e299
Benitez, Javier
aaf768e0-3166-4656-a787-89512ca1828c
Conejero, Raquel Andrés
9b719901-0ed9-45bc-a449-7eaca9de701a
Segota, Ena
fc15fd19-6953-4b3a-a1dd-fc244abab4c9
Weitzel, Jeffrey N
65e3e176-7d29-4f27-9eb9-4b62ab6ca0d4
Thelander, Margo
4db0c779-f41b-4bb0-afce-13558e5e500e
Peterlongo, Paolo
af3f3db4-e3fc-45db-bbb4-91954fe857fb
Radice, Paolo
d5bff2d9-ed03-4a8e-a9ca-f896a1666e2c
Pensotti, Valeria
afa26d92-d8fd-4ecc-b8b1-a1bc0e875b15
Dolcetti, Riccardo
0e929b00-e966-4ab8-9bd2-c6e39806199f
Bonanni, Bernardo
6ab53b39-2f33-42be-9c4e-eb577feb5124
Peissel, Bernard
94da3e26-04ab-4665-905a-aa21969c7a94
Zaffaroni, Daniela
f88dddd8-5392-415d-bbbb-c3d8e146ecb0
Scuvera, Giulietta
2e9e79c5-99a1-45b5-857a-c6bcff72c845
Manoukian, Siranoush
87f7b60d-b65f-4655-b1d8-3b7c5dcf37d2
Varesco, Liliana
07ebbeb9-3165-4a50-a227-d0896d53e86e
Capone, Gabriele L.
6a9d1a94-d8d1-48c8-9c48-d616520f149e
Papi, Laura
01bafe05-bdb9-4feb-953d-3def9b73baa8
Ottini, Laura
361443a8-6d75-4ea5-b1f8-f7a3b03f97a8
Yannoukakos, Drakoulis
b3f8728f-9538-4b45-84b1-dfe08bb0d3b8
Konstantopoulou, Irene
39dc052d-18ab-479a-abe2-7465b5727c1d
Garber, Judy
fdc6e441-ff06-4864-a716-75cb3a8a93de
Hamann, Ute
c47a5052-5e7b-492c-988b-38b7df2cffc6
Donaldson, Alan
8bd5454f-be4c-4b7a-ae31-c602f391920e
Brady, Angela
4fc55761-1e51-4e04-8463-73b72ea202e9
Brewer, Carole
f497c7f3-050d-4494-aecb-7e6a23101d18
Foo, Claire
03b27b44-b302-4973-9c4b-7f93ede629c0
Evans, D. Gareth
314acefb-89fb-4eb7-a0e7-0a6949c9af6c
Frost, Debra
38874d28-24d7-47b2-b458-b121539a3ceb
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Douglas, Fiona
a35f2e38-4fc4-481e-a212-1e3ae5d5ae0c
Cook, Jackie
b24e3336-f47a-4590-bc3f-7e2ab7d78e0d
Adlard, Julian
3a01574a-8ed1-4286-956c-c9e87fd89521
Barwell, Julian
775206d7-77c1-46bb-a6ff-932204a3c2f5
Walker, Lisa
682b9d2c-3469-416e-b9dc-a5c68626fba7
Izatt, Louise
5d6201a8-8a56-4923-ac9d-75dca6be0a40
Side, Lucy E.
f9e1faa2-2814-4c9e-8470-65d0f92ddcd6
Kennedy, M. John
8f7b041a-5c5e-415a-acc1-83192f80654c
Tischkowitz, Marc
3c5f5429-fb53-4c80-8a42-6cec37ab67bc
Rogers, Mark T.
4616db6a-cf85-4bee-82db-4538619dbb55
Porteous, Mary E.
05990ca3-1e88-43d9-983f-d1853589433b
Morrison, Patrick J.
0fb9bdda-83c3-446b-ae97-28858f06d2d8
Platte, Radka
23a1b828-b2b0-4504-a668-ce2e51888a52
Eeles, Ros
1101f5dc-f8ae-4102-99fb-f814695e5f9c
Davidson, Rosemarie
81692cd9-0a70-4a01-a68f-8eb623f0fbe0
Hodgson, Shirley
a9f6b2c4-f329-40b5-8b07-a74b3fdd1a0c
Cole, Trevor
5d7a1e62-1c71-4b07-acdd-652f08f153d4
Godwin, Andrew K.
a7e89dce-59e1-48f7-b668-42777f362435
Isaacs, Claudine
6e60951b-1f07-471a-8ca3-1941e83bbf83
Claes, Kathleen
d3e8b2a9-b47a-4d38-b130-91f309c4dc18
De Leeneer, Kim
2c477521-c736-44e5-bd0a-443b9e33c31a
Meindl, Alfons
10b41dbc-4030-4b19-976f-212367b636af
Gehrig, Andrea
39f42e5e-96be-4734-9ac9-0d4bf4cdcbae
Wappenschmidt, Barbara
b196c313-8a35-4e32-a020-10181ac41400
Sutter, Christian
c54383c2-0738-42cc-b0ab-c2595b4ec272
Engel, Christoph
e428d3b6-d668-487c-bcef-7d835e609751
Niederacher, Dieter
b6a4a233-f88d-416b-a22e-9902d732d8e6
Steinemann, Doris
4bfc199b-7277-4001-8e17-edc981effa55
Plendl, Hansjoerg
bb8b428f-344f-4e13-9c16-8017f573675c
Kast, Karin
7cde00f5-f897-4c84-bb86-2ecdd6e23b6d
Rhiem, Kerstin
5fbe374e-0810-4da0-a4fa-3e311fa952d7
Ditsch, Nina
f065f653-f2a5-4099-887b-65de0fb74d8c
Arnold, Norbert
2296ee7c-7ba5-48cb-8514-c0a9c4a25eb9
Varon-Mateeva, Raymonda
93a22b00-7e87-4296-b2da-82caf74bebfc
Schmutzler, Rita K.
bf790f2e-79f3-4151-a74c-793bf14d8f6a
Preisler-Adams, Sabine
82c50384-58e6-4299-a125-9b2c26413d32
Markov, Nadja Bogdanova
9ff1dcd1-9ef8-4ac8-8a7e-1a7b6f52b184
Wang-Gohrke, Shan
5bce864c-5f22-44d2-b5a0-b53a3e7abe8e
de Pauw, Antoine
1eaefe48-05cc-4f54-9af7-255b3e1ddbcc
Lefol, Cédrick
b5e25896-ddb6-41d5-8673-2c5f69094e4d
Lasset, Christine
b16ee5ce-49c4-4c51-b793-9d2b3a3d314a
Leroux, Dominique
8dfa1873-9146-46ec-8a9b-80d2825303d2
Rouleau, Etienne
a67d8f5c-91fe-4181-baa0-0fa27fa2879a
Damiola, Francesca
a2f2ca5e-88cb-49ae-ad15-623c4f778943
Dreyfus, Hélène
e2566ad7-4fd7-4422-be53-7eb6b4fce32b
Barjhoux, Laure
e5969462-17f0-4bed-b904-e30f6d246d5d
Golmard, Lisa
b0b52dde-c3d0-4608-a7a1-a750364f038c
Uhrhammer, Nancy
6cb3846f-12b6-45fa-b1d4-e55ba2b268f5
Bonadona, Valérie
4c4e4c27-c5eb-4325-b320-daa9301a8d1f
Sornin, Valérie
e8887767-8c61-4ebe-8a14-b45cdaf4ce9f
Bignon, Yves-Jean
cd1cb161-7fd1-4e32-86da-5e6a20fc611a
Carter, Jonathan
df759207-f431-469d-b97e-c4f2fa16292d
Van Le, Linda
6e234c51-55e2-4398-a08e-ba2fb6248e38
Piedmonte, Marion
db992162-8488-4999-b1e8-0c1cf10871e7
DiSilvestro, Paul A.
4ef5b4f3-4b55-405b-b788-16167e5adb53
de la Hoya, Miguel
8e170da0-2396-4f84-ba15-14fa2ad62fb2
Caldes, Trinidad
8caab9c0-bec3-44d5-8e98-c97ee3ebda7d
Nevanlinna, Heli
69be7a44-2abf-4504-a47b-a50b6723701b
Aittomäki, Kristiina
ac3ded8e-805e-4e49-9713-1e03062a2efc
Jager, Agnes
13a18349-d36a-4195-bee1-b7799131c523
van den Ouweland, Ans M.W.
e0480ef7-5da7-4b62-b2e1-525e6d69ed2d
Kets, Carolien M.
321538a4-e6cf-42d8-b492-57ae31523342
Aalfs, Cora M.
c180e9a9-29e4-4916-afff-fdc2ed1d58c1
van Leeuwen, Flora E.
89d7c75b-228f-4c71-828b-c92b5e5ae42e
Hogervorst, Frans B.L.
ed37f627-0663-44d8-9067-e921fd700909
Meijers-Heijboer, Hanne E.J.
1662d152-1979-4cea-a8ba-49242bf0985b
Oosterwijk, Jan C.
281f3aba-7b6a-4ce5-a1c6-a71194155181
van Roozendaal, Kees E.P.
b04bff2b-903d-4df3-bb92-0d4d1e4a81a6
Rookus, Matti A.
9773a738-9a67-460f-9305-ecf35893eda2
Devilee, Peter
70de16eb-ec65-4e3e-b8f7-6333896e213f
van der Luijt, Rob B.
382af51c-839b-4d04-9274-34878f862fed
Olah, Edith
f4ee7e40-b263-490e-96fc-84b98eb2ec20
Diez, Orland
35522b1a-2862-43ce-b8e9-50f60579c671
Teulé, Alex
a71b36ee-6358-46b3-82b8-2cc5538418dc
Lazaro, Conxi
34576bd1-4cfb-4b16-9a51-78bdd7057bd7
Blanco, Ignacio
27cfc95d-deca-4fc4-8bfb-c162edd24e0e
Del Valle, Jesús
508534e0-f1b6-4da1-bbea-31baae8da021
Jakubowska, Anna
ecdb73a5-85f8-49ba-b03e-dcf4b559d5b1
Sukiennicki, Grzegorz
99a55eea-9b35-4a45-81a0-d645d84f94ad
Gronwald, Jacek
4a0117ac-84f8-4351-a97d-637a60db25f6
Lubinski, Jan
e7a9709c-36b3-44ed-a5e0-675177ca3d51
Durda, Katarzyna
61bc19e0-811f-49a7-93c9-120f84525fda
Jaworska-Bieniek, Katarzyna
7b6b105c-f5a8-497a-a5e8-59512b6e7047
Agnarsson, Bjarni A.
f0ee7b50-2f4c-4a48-a111-9bd279925eff
Maugard, Christine
ad4c97d3-4a43-4752-917e-7d54b4e80769
Amadori, Alberto
c819f15a-317d-492f-bace-2743fd83f14b
Montagna, Marco
1e04949f-87c3-4ca4-a772-5d59a9407f07
Teixeira, Manuel R.
14fa26a0-c652-4dc1-a57f-38569d5dfe47
Spurdle, Amanda B.
8158d468-cc96-4e39-9bac-fcaaa7061a72
Foulkes, William
f49bd7f8-0cd2-4ed3-a46c-2aaee6cca69c
Olswold, Curtis
b656d490-112e-4cc1-a912-a17606ce2dc9
Lindor, Noralane M.
95f60dee-421b-4055-a396-a3b05371762f
Pankratz, Vernon S.
7e7d7585-2ef3-4b56-a355-3cd5eefcf0c6
Szabo, Csilla I
10b9a391-4ba2-438e-9b63-2620f7d792f7
Lincoln, Anne
48229579-52e3-45b2-8240-4a0a8fdddfe6
Jacobs, Lauren
f65bf538-c394-4bc9-8dae-e65e33c39401
Corines, Marina
3c069ee0-62a3-4c5f-a9a2-517a515ce440
Robson, Mark
c5e6e973-8fbe-4efd-b2b3-84c885e18b4c
Vijai, Joseph
f3405060-d901-46b7-acd0-d60988e5e1fd
Berger, Andreas
97715c2d-0088-46f4-8fc4-7d7d7a66d747
Fink-Retter, Anneliese
5204f14d-94b4-4fa8-9886-3b2dbd00274a
Singer, Christian F.
3ac2e574-0627-4715-ac4a-8ab7edcc3851
Rappaport, Christine
6601215f-18f5-482d-b6c0-b0ee380786b6
Kaulich, Daphne Geschwantler
6ee09334-1d47-4be9-b1f2-fcce9ddbb174
Pfeiler, Georg
900ce095-ab28-4246-ad45-d7c7d19da9e2
Tea, Muy-Kheng
c21496ab-36fe-4d20-856e-2fc2afec0669
Greene, Mark H.
aefbcd26-0def-47a3-8580-0c56feb03756
Mai, Phuong L.
31cb800d-d6a7-4aa0-b590-4e8668ce303a
Rennert, Gad
76f7951d-133b-4b7e-86a2-175be20d775d
Imyanitov, Evgeny N.
fcad02c1-95af-47aa-9b1b-3ea64cd20d99
Mulligan, Anna Marie
a999fb4f-9064-4311-90fc-3e8e80a5458a
Glendon, Gord
35cee1ee-d423-47d9-af69-f41d99fb9230
Andrulis, Irene L.
bc0d05b1-2437-452a-b9df-0d31cfbe1435
Tchatchou, Sandrine
ec368f3f-0af9-4678-87fa-edb301f4d24e
Toland, Amanda Ewart
edbfce4b-35a4-461c-8b4f-b7f8d5497ec8
Pedersen, Inge Sokilde
6ce8bd5a-02fb-4fad-a845-e0b78cdd6dec
Thomassen, Mads
c7c9230a-4f3d-42d0-89f1-b5a36d431aae
Kruse, Torben A.
b53a27bc-4eda-44dd-b479-345f5dfda90f
Jensen, Uffe Birk
1d7b3fd2-94fc-448f-8b0e-2a5d66815233
Caligo, Maria A.
8fd95b7b-5e69-4f7f-9513-50b3d5e86ef6
Friedman, Eitan
764d4102-31ee-4826-ad68-0da74dba88f2
Zidan, Jamal
7e6d680a-c11f-4ddb-bedd-0d9d0a6bf22e
Laitman, Yael
d2aba8bd-dcba-47cb-b687-ebfcd76c1b3b
Lindblom, Annika
855a20de-8712-44cb-9a0a-01d4176a666f
Melin, Beatrice
0c450d80-5bc8-4612-98fb-26dd1d0c6706
Arver, Brita
179b96e1-1740-455d-a2bc-8e4ad32fb887
Loman, Niklas
e075acfa-7d57-4782-b4ba-cb0bb472b25c
Rosenquist, Richard
6a175d34-f0e0-4291-ab9f-9a12517e5165
Olopade, Olufunmilayo I.
c926d080-7dfd-49f7-ab2f-95a8e24365cc
Nussbaum, Robert L.
050ecb33-a74c-4553-8e33-793931e86b13
Ramus, Susan J.
f2a91d0b-8aab-4e57-b49f-7637767b4f57
Nathanson, Katherine L.
595fa51d-4601-446d-85ff-9151c5f9246a
Domchek, Susan M.
7d99c293-81c9-4f0e-ab2c-e2655e2b601e
Rebbeck, Timothy R.
017e04fa-fcd5-48d2-89f5-2e05f4c2091a
Arun, Banu K.
af71f3d6-59d3-44f8-9a29-6c1b3c909b11
Mitchell, Gillian
5091b5ee-dac1-4a68-8b4f-9ec2dbc198e4
Karlan, Beth Y.
0a74d552-f43d-4670-bc0c-0f860d55b15e
Lester, Jenny
1f4b45ae-2ac5-4797-bd24-faf476437ecb
Orsulic, Sandra
db3fd4b9-161c-4ee9-9113-1b75f9df34c0
Stoppa-Lyonnet, Dominique
c110a3bd-17a1-4b82-9b32-75728172bfc5
Thomas, Gilles
3abaa4db-649d-4e6b-8833-de4224f5f13b
Simard, Jacques
6269fd00-31ae-40f0-b016-5f60cb9f5b96
Couch, Fergus J.
778e32f1-0b19-4cf4-b38f-69dd027cad3a
Offit, Kenneth
ce1fc8a6-b5ac-434a-9d2d-4a7e1ee7ca7c
Easton, Douglas F.
2661cf5e-8fc6-4f1d-b27a-e60cac8c8819
Chenevix-Trench, Georgia
7d222914-c6e5-47b8-9022-5874b7c82a3e
Antoniou, Antonis C.
b5275276-df7e-42a4-9a38-6a9516924f0d
Mazoyer, Sylvie
6e0e32e4-7d0e-4c7c-bd80-d221d53af542
Phelan, Catherine M.
0692189d-5402-41da-a627-acc6ba0c6505
Sinilnikova, Olga M.
17bb19c7-8db3-48e3-8630-0c9a78a2e1a4
Cox, David G.
ac55f960-d0f3-4477-b8a7-30743fce0123
Blein, Sophie
4194da3c-87b1-4fa5-8fa5-89f4dc05ee78
Bardel, Claire
1f85d56e-1fd8-47fb-b8d2-f25163b52041
Danjean, Vincent
61ea72c4-de51-423a-96d9-30afef7dfe5b
McGuffog, Lesley
21522096-38bb-45df-aa56-caf2f27d7254
Healey, Sue
5d595192-5381-464d-85cc-71ad09a05065
Barrowdale, Daniel
507bc817-9e80-4ff2-a379-470e0d6ed2c9
Lee, Andrew
a82db836-29cd-4bf5-a96a-fb6af545b310
Dennis, Joe
bd305c84-d968-4946-b154-a5bedb469210
Kuchenbaecker, Karoline B.
c72c2a25-9297-47bc-a4c0-f6e135ed0854
Soucy, Penny
c8606457-7865-44a4-90ce-de2b55994738
Terry, Mary Beth
f4e42578-34d7-4e36-a71d-2c174d62b9c3
Chung, Wendy K.
c7c336a6-b597-432b-b8df-abd1a2d3de14
Goldgar, David E.
102af7b6-41ab-46c0-9d76-43359c897e2e
Buys, Saundra S.
5b1a7cea-6562-4fb0-b2a9-06b08d5e86e6
Janavicius, Ramunas
314ff9ed-91c2-49cc-aa80-5ab072225a98
Tihomirova, Laima
b3d01d1c-8064-4610-ab37-0b9c169a027c
Tung, Nadine
9a999423-a6aa-41a5-957f-2d788ee3da15
Dorfling, Cecilia M.
e277a79f-0fec-4028-9408-5b8624ea05c6
van Rensburg, Elizabeth J.
d4dd3b97-d9ee-4968-97f4-4e8aa97c574a
Neuhausen, Susan L.
7cb359d3-5964-460c-ad60-63b77368c042
Ding, Yuan Chun
107aa0a1-2546-46b0-a1e5-a9d6dcb26744
Gerdes, Anne-Marie
60e03234-c7bd-4659-a642-432c0f943474
Ejlertsen, Bent
b9f56a71-7d7c-4a1d-98d2-fdd32e7a3ad7
Nielsen, Finn C
e3773c0a-25a2-4cc2-8120-3d7de8394da3
Hansen, Thomas VO
f679b4a0-4065-470a-83ca-3f4efee13213
Osorio, Ana
5d37d9d7-d889-4e14-ad7c-7b7f73f6e299
Benitez, Javier
aaf768e0-3166-4656-a787-89512ca1828c
Conejero, Raquel Andrés
9b719901-0ed9-45bc-a449-7eaca9de701a
Segota, Ena
fc15fd19-6953-4b3a-a1dd-fc244abab4c9
Weitzel, Jeffrey N
65e3e176-7d29-4f27-9eb9-4b62ab6ca0d4
Thelander, Margo
4db0c779-f41b-4bb0-afce-13558e5e500e
Peterlongo, Paolo
af3f3db4-e3fc-45db-bbb4-91954fe857fb
Radice, Paolo
d5bff2d9-ed03-4a8e-a9ca-f896a1666e2c
Pensotti, Valeria
afa26d92-d8fd-4ecc-b8b1-a1bc0e875b15
Dolcetti, Riccardo
0e929b00-e966-4ab8-9bd2-c6e39806199f
Bonanni, Bernardo
6ab53b39-2f33-42be-9c4e-eb577feb5124
Peissel, Bernard
94da3e26-04ab-4665-905a-aa21969c7a94
Zaffaroni, Daniela
f88dddd8-5392-415d-bbbb-c3d8e146ecb0
Scuvera, Giulietta
2e9e79c5-99a1-45b5-857a-c6bcff72c845
Manoukian, Siranoush
87f7b60d-b65f-4655-b1d8-3b7c5dcf37d2
Varesco, Liliana
07ebbeb9-3165-4a50-a227-d0896d53e86e
Capone, Gabriele L.
6a9d1a94-d8d1-48c8-9c48-d616520f149e
Papi, Laura
01bafe05-bdb9-4feb-953d-3def9b73baa8
Ottini, Laura
361443a8-6d75-4ea5-b1f8-f7a3b03f97a8
Yannoukakos, Drakoulis
b3f8728f-9538-4b45-84b1-dfe08bb0d3b8
Konstantopoulou, Irene
39dc052d-18ab-479a-abe2-7465b5727c1d
Garber, Judy
fdc6e441-ff06-4864-a716-75cb3a8a93de
Hamann, Ute
c47a5052-5e7b-492c-988b-38b7df2cffc6
Donaldson, Alan
8bd5454f-be4c-4b7a-ae31-c602f391920e
Brady, Angela
4fc55761-1e51-4e04-8463-73b72ea202e9
Brewer, Carole
f497c7f3-050d-4494-aecb-7e6a23101d18
Foo, Claire
03b27b44-b302-4973-9c4b-7f93ede629c0
Evans, D. Gareth
314acefb-89fb-4eb7-a0e7-0a6949c9af6c
Frost, Debra
38874d28-24d7-47b2-b458-b121539a3ceb
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Douglas, Fiona
a35f2e38-4fc4-481e-a212-1e3ae5d5ae0c
Cook, Jackie
b24e3336-f47a-4590-bc3f-7e2ab7d78e0d
Adlard, Julian
3a01574a-8ed1-4286-956c-c9e87fd89521
Barwell, Julian
775206d7-77c1-46bb-a6ff-932204a3c2f5
Walker, Lisa
682b9d2c-3469-416e-b9dc-a5c68626fba7
Izatt, Louise
5d6201a8-8a56-4923-ac9d-75dca6be0a40
Side, Lucy E.
f9e1faa2-2814-4c9e-8470-65d0f92ddcd6
Kennedy, M. John
8f7b041a-5c5e-415a-acc1-83192f80654c
Tischkowitz, Marc
3c5f5429-fb53-4c80-8a42-6cec37ab67bc
Rogers, Mark T.
4616db6a-cf85-4bee-82db-4538619dbb55
Porteous, Mary E.
05990ca3-1e88-43d9-983f-d1853589433b
Morrison, Patrick J.
0fb9bdda-83c3-446b-ae97-28858f06d2d8
Platte, Radka
23a1b828-b2b0-4504-a668-ce2e51888a52
Eeles, Ros
1101f5dc-f8ae-4102-99fb-f814695e5f9c
Davidson, Rosemarie
81692cd9-0a70-4a01-a68f-8eb623f0fbe0
Hodgson, Shirley
a9f6b2c4-f329-40b5-8b07-a74b3fdd1a0c
Cole, Trevor
5d7a1e62-1c71-4b07-acdd-652f08f153d4
Godwin, Andrew K.
a7e89dce-59e1-48f7-b668-42777f362435
Isaacs, Claudine
6e60951b-1f07-471a-8ca3-1941e83bbf83
Claes, Kathleen
d3e8b2a9-b47a-4d38-b130-91f309c4dc18
De Leeneer, Kim
2c477521-c736-44e5-bd0a-443b9e33c31a
Meindl, Alfons
10b41dbc-4030-4b19-976f-212367b636af
Gehrig, Andrea
39f42e5e-96be-4734-9ac9-0d4bf4cdcbae
Wappenschmidt, Barbara
b196c313-8a35-4e32-a020-10181ac41400
Sutter, Christian
c54383c2-0738-42cc-b0ab-c2595b4ec272
Engel, Christoph
e428d3b6-d668-487c-bcef-7d835e609751
Niederacher, Dieter
b6a4a233-f88d-416b-a22e-9902d732d8e6
Steinemann, Doris
4bfc199b-7277-4001-8e17-edc981effa55
Plendl, Hansjoerg
bb8b428f-344f-4e13-9c16-8017f573675c
Kast, Karin
7cde00f5-f897-4c84-bb86-2ecdd6e23b6d
Rhiem, Kerstin
5fbe374e-0810-4da0-a4fa-3e311fa952d7
Ditsch, Nina
f065f653-f2a5-4099-887b-65de0fb74d8c
Arnold, Norbert
2296ee7c-7ba5-48cb-8514-c0a9c4a25eb9
Varon-Mateeva, Raymonda
93a22b00-7e87-4296-b2da-82caf74bebfc
Schmutzler, Rita K.
bf790f2e-79f3-4151-a74c-793bf14d8f6a
Preisler-Adams, Sabine
82c50384-58e6-4299-a125-9b2c26413d32
Markov, Nadja Bogdanova
9ff1dcd1-9ef8-4ac8-8a7e-1a7b6f52b184
Wang-Gohrke, Shan
5bce864c-5f22-44d2-b5a0-b53a3e7abe8e
de Pauw, Antoine
1eaefe48-05cc-4f54-9af7-255b3e1ddbcc
Lefol, Cédrick
b5e25896-ddb6-41d5-8673-2c5f69094e4d
Lasset, Christine
b16ee5ce-49c4-4c51-b793-9d2b3a3d314a
Leroux, Dominique
8dfa1873-9146-46ec-8a9b-80d2825303d2
Rouleau, Etienne
a67d8f5c-91fe-4181-baa0-0fa27fa2879a
Damiola, Francesca
a2f2ca5e-88cb-49ae-ad15-623c4f778943
Dreyfus, Hélène
e2566ad7-4fd7-4422-be53-7eb6b4fce32b
Barjhoux, Laure
e5969462-17f0-4bed-b904-e30f6d246d5d
Golmard, Lisa
b0b52dde-c3d0-4608-a7a1-a750364f038c
Uhrhammer, Nancy
6cb3846f-12b6-45fa-b1d4-e55ba2b268f5
Bonadona, Valérie
4c4e4c27-c5eb-4325-b320-daa9301a8d1f
Sornin, Valérie
e8887767-8c61-4ebe-8a14-b45cdaf4ce9f
Bignon, Yves-Jean
cd1cb161-7fd1-4e32-86da-5e6a20fc611a
Carter, Jonathan
df759207-f431-469d-b97e-c4f2fa16292d
Van Le, Linda
6e234c51-55e2-4398-a08e-ba2fb6248e38
Piedmonte, Marion
db992162-8488-4999-b1e8-0c1cf10871e7
DiSilvestro, Paul A.
4ef5b4f3-4b55-405b-b788-16167e5adb53
de la Hoya, Miguel
8e170da0-2396-4f84-ba15-14fa2ad62fb2
Caldes, Trinidad
8caab9c0-bec3-44d5-8e98-c97ee3ebda7d
Nevanlinna, Heli
69be7a44-2abf-4504-a47b-a50b6723701b
Aittomäki, Kristiina
ac3ded8e-805e-4e49-9713-1e03062a2efc
Jager, Agnes
13a18349-d36a-4195-bee1-b7799131c523
van den Ouweland, Ans M.W.
e0480ef7-5da7-4b62-b2e1-525e6d69ed2d
Kets, Carolien M.
321538a4-e6cf-42d8-b492-57ae31523342
Aalfs, Cora M.
c180e9a9-29e4-4916-afff-fdc2ed1d58c1
van Leeuwen, Flora E.
89d7c75b-228f-4c71-828b-c92b5e5ae42e
Hogervorst, Frans B.L.
ed37f627-0663-44d8-9067-e921fd700909
Meijers-Heijboer, Hanne E.J.
1662d152-1979-4cea-a8ba-49242bf0985b
Oosterwijk, Jan C.
281f3aba-7b6a-4ce5-a1c6-a71194155181
van Roozendaal, Kees E.P.
b04bff2b-903d-4df3-bb92-0d4d1e4a81a6
Rookus, Matti A.
9773a738-9a67-460f-9305-ecf35893eda2
Devilee, Peter
70de16eb-ec65-4e3e-b8f7-6333896e213f
van der Luijt, Rob B.
382af51c-839b-4d04-9274-34878f862fed
Olah, Edith
f4ee7e40-b263-490e-96fc-84b98eb2ec20
Diez, Orland
35522b1a-2862-43ce-b8e9-50f60579c671
Teulé, Alex
a71b36ee-6358-46b3-82b8-2cc5538418dc
Lazaro, Conxi
34576bd1-4cfb-4b16-9a51-78bdd7057bd7
Blanco, Ignacio
27cfc95d-deca-4fc4-8bfb-c162edd24e0e
Del Valle, Jesús
508534e0-f1b6-4da1-bbea-31baae8da021
Jakubowska, Anna
ecdb73a5-85f8-49ba-b03e-dcf4b559d5b1
Sukiennicki, Grzegorz
99a55eea-9b35-4a45-81a0-d645d84f94ad
Gronwald, Jacek
4a0117ac-84f8-4351-a97d-637a60db25f6
Lubinski, Jan
e7a9709c-36b3-44ed-a5e0-675177ca3d51
Durda, Katarzyna
61bc19e0-811f-49a7-93c9-120f84525fda
Jaworska-Bieniek, Katarzyna
7b6b105c-f5a8-497a-a5e8-59512b6e7047
Agnarsson, Bjarni A.
f0ee7b50-2f4c-4a48-a111-9bd279925eff
Maugard, Christine
ad4c97d3-4a43-4752-917e-7d54b4e80769
Amadori, Alberto
c819f15a-317d-492f-bace-2743fd83f14b
Montagna, Marco
1e04949f-87c3-4ca4-a772-5d59a9407f07
Teixeira, Manuel R.
14fa26a0-c652-4dc1-a57f-38569d5dfe47
Spurdle, Amanda B.
8158d468-cc96-4e39-9bac-fcaaa7061a72
Foulkes, William
f49bd7f8-0cd2-4ed3-a46c-2aaee6cca69c
Olswold, Curtis
b656d490-112e-4cc1-a912-a17606ce2dc9
Lindor, Noralane M.
95f60dee-421b-4055-a396-a3b05371762f
Pankratz, Vernon S.
7e7d7585-2ef3-4b56-a355-3cd5eefcf0c6
Szabo, Csilla I
10b9a391-4ba2-438e-9b63-2620f7d792f7
Lincoln, Anne
48229579-52e3-45b2-8240-4a0a8fdddfe6
Jacobs, Lauren
f65bf538-c394-4bc9-8dae-e65e33c39401
Corines, Marina
3c069ee0-62a3-4c5f-a9a2-517a515ce440
Robson, Mark
c5e6e973-8fbe-4efd-b2b3-84c885e18b4c
Vijai, Joseph
f3405060-d901-46b7-acd0-d60988e5e1fd
Berger, Andreas
97715c2d-0088-46f4-8fc4-7d7d7a66d747
Fink-Retter, Anneliese
5204f14d-94b4-4fa8-9886-3b2dbd00274a
Singer, Christian F.
3ac2e574-0627-4715-ac4a-8ab7edcc3851
Rappaport, Christine
6601215f-18f5-482d-b6c0-b0ee380786b6
Kaulich, Daphne Geschwantler
6ee09334-1d47-4be9-b1f2-fcce9ddbb174
Pfeiler, Georg
900ce095-ab28-4246-ad45-d7c7d19da9e2
Tea, Muy-Kheng
c21496ab-36fe-4d20-856e-2fc2afec0669
Greene, Mark H.
aefbcd26-0def-47a3-8580-0c56feb03756
Mai, Phuong L.
31cb800d-d6a7-4aa0-b590-4e8668ce303a
Rennert, Gad
76f7951d-133b-4b7e-86a2-175be20d775d
Imyanitov, Evgeny N.
fcad02c1-95af-47aa-9b1b-3ea64cd20d99
Mulligan, Anna Marie
a999fb4f-9064-4311-90fc-3e8e80a5458a
Glendon, Gord
35cee1ee-d423-47d9-af69-f41d99fb9230
Andrulis, Irene L.
bc0d05b1-2437-452a-b9df-0d31cfbe1435
Tchatchou, Sandrine
ec368f3f-0af9-4678-87fa-edb301f4d24e
Toland, Amanda Ewart
edbfce4b-35a4-461c-8b4f-b7f8d5497ec8
Pedersen, Inge Sokilde
6ce8bd5a-02fb-4fad-a845-e0b78cdd6dec
Thomassen, Mads
c7c9230a-4f3d-42d0-89f1-b5a36d431aae
Kruse, Torben A.
b53a27bc-4eda-44dd-b479-345f5dfda90f
Jensen, Uffe Birk
1d7b3fd2-94fc-448f-8b0e-2a5d66815233
Caligo, Maria A.
8fd95b7b-5e69-4f7f-9513-50b3d5e86ef6
Friedman, Eitan
764d4102-31ee-4826-ad68-0da74dba88f2
Zidan, Jamal
7e6d680a-c11f-4ddb-bedd-0d9d0a6bf22e
Laitman, Yael
d2aba8bd-dcba-47cb-b687-ebfcd76c1b3b
Lindblom, Annika
855a20de-8712-44cb-9a0a-01d4176a666f
Melin, Beatrice
0c450d80-5bc8-4612-98fb-26dd1d0c6706
Arver, Brita
179b96e1-1740-455d-a2bc-8e4ad32fb887
Loman, Niklas
e075acfa-7d57-4782-b4ba-cb0bb472b25c
Rosenquist, Richard
6a175d34-f0e0-4291-ab9f-9a12517e5165
Olopade, Olufunmilayo I.
c926d080-7dfd-49f7-ab2f-95a8e24365cc
Nussbaum, Robert L.
050ecb33-a74c-4553-8e33-793931e86b13
Ramus, Susan J.
f2a91d0b-8aab-4e57-b49f-7637767b4f57
Nathanson, Katherine L.
595fa51d-4601-446d-85ff-9151c5f9246a
Domchek, Susan M.
7d99c293-81c9-4f0e-ab2c-e2655e2b601e
Rebbeck, Timothy R.
017e04fa-fcd5-48d2-89f5-2e05f4c2091a
Arun, Banu K.
af71f3d6-59d3-44f8-9a29-6c1b3c909b11
Mitchell, Gillian
5091b5ee-dac1-4a68-8b4f-9ec2dbc198e4
Karlan, Beth Y.
0a74d552-f43d-4670-bc0c-0f860d55b15e
Lester, Jenny
1f4b45ae-2ac5-4797-bd24-faf476437ecb
Orsulic, Sandra
db3fd4b9-161c-4ee9-9113-1b75f9df34c0
Stoppa-Lyonnet, Dominique
c110a3bd-17a1-4b82-9b32-75728172bfc5
Thomas, Gilles
3abaa4db-649d-4e6b-8833-de4224f5f13b
Simard, Jacques
6269fd00-31ae-40f0-b016-5f60cb9f5b96
Couch, Fergus J.
778e32f1-0b19-4cf4-b38f-69dd027cad3a
Offit, Kenneth
ce1fc8a6-b5ac-434a-9d2d-4a7e1ee7ca7c
Easton, Douglas F.
2661cf5e-8fc6-4f1d-b27a-e60cac8c8819
Chenevix-Trench, Georgia
7d222914-c6e5-47b8-9022-5874b7c82a3e
Antoniou, Antonis C.
b5275276-df7e-42a4-9a38-6a9516924f0d
Mazoyer, Sylvie
6e0e32e4-7d0e-4c7c-bd80-d221d53af542
Phelan, Catherine M.
0692189d-5402-41da-a627-acc6ba0c6505
Sinilnikova, Olga M.
17bb19c7-8db3-48e3-8630-0c9a78a2e1a4
Cox, David G.
ac55f960-d0f3-4477-b8a7-30743fce0123

Blein, Sophie, Bardel, Claire and Danjean, Vincent et al. (2015) An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers. Breast Cancer Research, 17 (1), 1-15. (doi:10.1186/s13058-015-0567-2). (PMID:25925750)

Record type: Article

Abstract

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.

PDF
__userfiles.soton.ac.uk_Users_slb1_mydesktop_s13058-015-0567-2.pdf - Other
Available under License Creative Commons Attribution.
Download (1MB)

More information

Accepted/In Press date: 25 March 2015
Published date: 27 April 2015
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 382468
URI: https://eprints.soton.ac.uk/id/eprint/382468
PURE UUID: 317dcb68-d0e6-4715-b360-b8c7668d7912

Catalogue record

Date deposited: 05 Oct 2015 13:57
Last modified: 17 Jul 2017 20:20

Export record

Altmetrics

Contributors

Author: Sophie Blein
Author: Claire Bardel
Author: Vincent Danjean
Author: Lesley McGuffog
Author: Sue Healey
Author: Daniel Barrowdale
Author: Andrew Lee
Author: Joe Dennis
Author: Karoline B. Kuchenbaecker
Author: Penny Soucy
Author: Mary Beth Terry
Author: Wendy K. Chung
Author: David E. Goldgar
Author: Saundra S. Buys
Author: Ramunas Janavicius
Author: Laima Tihomirova
Author: Nadine Tung
Author: Cecilia M. Dorfling
Author: Elizabeth J. van Rensburg
Author: Susan L. Neuhausen
Author: Yuan Chun Ding
Author: Anne-Marie Gerdes
Author: Bent Ejlertsen
Author: Finn C Nielsen
Author: Thomas VO Hansen
Author: Ana Osorio
Author: Javier Benitez
Author: Raquel Andrés Conejero
Author: Ena Segota
Author: Jeffrey N Weitzel
Author: Margo Thelander
Author: Paolo Peterlongo
Author: Paolo Radice
Author: Valeria Pensotti
Author: Riccardo Dolcetti
Author: Bernardo Bonanni
Author: Bernard Peissel
Author: Daniela Zaffaroni
Author: Giulietta Scuvera
Author: Siranoush Manoukian
Author: Liliana Varesco
Author: Gabriele L. Capone
Author: Laura Papi
Author: Laura Ottini
Author: Drakoulis Yannoukakos
Author: Irene Konstantopoulou
Author: Judy Garber
Author: Ute Hamann
Author: Alan Donaldson
Author: Angela Brady
Author: Carole Brewer
Author: Claire Foo
Author: D. Gareth Evans
Author: Debra Frost
Author: Diana Eccles
Author: Fiona Douglas
Author: Jackie Cook
Author: Julian Adlard
Author: Julian Barwell
Author: Lisa Walker
Author: Louise Izatt
Author: Lucy E. Side
Author: M. John Kennedy
Author: Marc Tischkowitz
Author: Mark T. Rogers
Author: Mary E. Porteous
Author: Patrick J. Morrison
Author: Radka Platte
Author: Ros Eeles
Author: Rosemarie Davidson
Author: Shirley Hodgson
Author: Trevor Cole
Author: Andrew K. Godwin
Author: Claudine Isaacs
Author: Kathleen Claes
Author: Kim De Leeneer
Author: Alfons Meindl
Author: Andrea Gehrig
Author: Barbara Wappenschmidt
Author: Christian Sutter
Author: Christoph Engel
Author: Dieter Niederacher
Author: Doris Steinemann
Author: Hansjoerg Plendl
Author: Karin Kast
Author: Kerstin Rhiem
Author: Nina Ditsch
Author: Norbert Arnold
Author: Raymonda Varon-Mateeva
Author: Rita K. Schmutzler
Author: Sabine Preisler-Adams
Author: Nadja Bogdanova Markov
Author: Shan Wang-Gohrke
Author: Antoine de Pauw
Author: Cédrick Lefol
Author: Christine Lasset
Author: Dominique Leroux
Author: Etienne Rouleau
Author: Francesca Damiola
Author: Hélène Dreyfus
Author: Laure Barjhoux
Author: Lisa Golmard
Author: Nancy Uhrhammer
Author: Valérie Bonadona
Author: Valérie Sornin
Author: Yves-Jean Bignon
Author: Jonathan Carter
Author: Linda Van Le
Author: Marion Piedmonte
Author: Paul A. DiSilvestro
Author: Miguel de la Hoya
Author: Trinidad Caldes
Author: Heli Nevanlinna
Author: Kristiina Aittomäki
Author: Agnes Jager
Author: Ans M.W. van den Ouweland
Author: Carolien M. Kets
Author: Cora M. Aalfs
Author: Flora E. van Leeuwen
Author: Frans B.L. Hogervorst
Author: Hanne E.J. Meijers-Heijboer
Author: Jan C. Oosterwijk
Author: Kees E.P. van Roozendaal
Author: Matti A. Rookus
Author: Peter Devilee
Author: Rob B. van der Luijt
Author: Edith Olah
Author: Orland Diez
Author: Alex Teulé
Author: Conxi Lazaro
Author: Ignacio Blanco
Author: Jesús Del Valle
Author: Anna Jakubowska
Author: Grzegorz Sukiennicki
Author: Jacek Gronwald
Author: Jan Lubinski
Author: Katarzyna Durda
Author: Katarzyna Jaworska-Bieniek
Author: Bjarni A. Agnarsson
Author: Christine Maugard
Author: Alberto Amadori
Author: Marco Montagna
Author: Manuel R. Teixeira
Author: Amanda B. Spurdle
Author: William Foulkes
Author: Curtis Olswold
Author: Noralane M. Lindor
Author: Vernon S. Pankratz
Author: Csilla I Szabo
Author: Anne Lincoln
Author: Lauren Jacobs
Author: Marina Corines
Author: Mark Robson
Author: Joseph Vijai
Author: Andreas Berger
Author: Anneliese Fink-Retter
Author: Christian F. Singer
Author: Christine Rappaport
Author: Daphne Geschwantler Kaulich
Author: Georg Pfeiler
Author: Muy-Kheng Tea
Author: Mark H. Greene
Author: Phuong L. Mai
Author: Gad Rennert
Author: Evgeny N. Imyanitov
Author: Anna Marie Mulligan
Author: Gord Glendon
Author: Irene L. Andrulis
Author: Sandrine Tchatchou
Author: Amanda Ewart Toland
Author: Inge Sokilde Pedersen
Author: Mads Thomassen
Author: Torben A. Kruse
Author: Uffe Birk Jensen
Author: Maria A. Caligo
Author: Eitan Friedman
Author: Jamal Zidan
Author: Yael Laitman
Author: Annika Lindblom
Author: Beatrice Melin
Author: Brita Arver
Author: Niklas Loman
Author: Richard Rosenquist
Author: Olufunmilayo I. Olopade
Author: Robert L. Nussbaum
Author: Susan J. Ramus
Author: Katherine L. Nathanson
Author: Susan M. Domchek
Author: Timothy R. Rebbeck
Author: Banu K. Arun
Author: Gillian Mitchell
Author: Beth Y. Karlan
Author: Jenny Lester
Author: Sandra Orsulic
Author: Dominique Stoppa-Lyonnet
Author: Gilles Thomas
Author: Jacques Simard
Author: Fergus J. Couch
Author: Kenneth Offit
Author: Douglas F. Easton
Author: Georgia Chenevix-Trench
Author: Antonis C. Antoniou
Author: Sylvie Mazoyer
Author: Catherine M. Phelan
Author: Olga M. Sinilnikova
Author: David G. Cox

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×