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Br J Cancer. 2011 Apr 12;104(8):1356-61. doi: 10.1038/bjc.2011.91. Epub 2011 Mar 22.

Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2.

Collaborators (149)

Hogervorst FB, Verhoef S, Verheus M, van 't Veer LJ, van Leeuwen FE, Rookus MA, Collée M, van den Ouweland AM, Jager A, Hooning MJ, Tilanus-Linthorst MM, Seynaeve C, van Asperen CJ, Wijnen JT, Vreeswijk MP, Tollenaar RA, Devilee P, Ligtenberg MJ, Hoogerbrugge N, Ausems MG, van der Luijt RB, Aalfs CM, van Os TA, Gille JJ, Waisfisz Q, Meijers-Heijboer HE, Gomez-Garcia EB, van Roozendaal CE, Blok MJ, Caanen B, Oosterwijk JC, van der Hout AH, Mourits MJ, Vasen HF, Peock S, Cook M, Oliver C, Frost D, Miedzybrodzka Z, Gregory H, Morrison P, Jeffers L, Cole T, McKeown C, Ong KR, Hoffman J, Donaldson A, Paterson J, Downing S, Taylor A, Murray A, Rogers MT, McCann E, Kennedy MJ, Barton D, East S, Porteous M, Drummond S, Brewer C, Kivuva E, Searle A, Goodman S, Hill K, Davidson R, Bradshaw N, Snadden L, Longmuir M, Watt C, Gibson S, Izatt L, Jacobs C, Langman C, Whaite A, Dorkins H, Barwell J, Adlard J, Chu C, Miller J, Ellis I, Evans DG, Lalloo F, Taylor J, Side L, Male A, Berlin C, Eason J, Collier R, Douglas F, Claber O, Walker L, McLeod D, Halliday D, Durell S, Stayner B, Eeles R, Shanley S, Rahman N, Houlston R, Bancroft E, D'Mello L, Page E, Ardern-Jones A, Kohut K, Wiggins J, Castro E, Mitra A, Robertson L, Cook J, Quarrell O, Bardsley C, Hodgson S, Goff S, Brice G, Winchester L, Eddy C, Tripathi V, Attard V, Eccles D, Lucassen A, Crawford G, McBride D, Smalley S, Godwin AK, Karlsson P, Nordling M, Bergman A, Einbeigi Z, Stenmark- Askmalm M, Liedgren S, Borg A, Loman N, Olsson H, Kristoffersson U, Jernström H, Harbst K, Henriksson K, Lindblom A, Arver B, Wachenfeldt Av, Liljegren A, Barbany-Bustinza G, Rantala J, Melin B, Grönberg H, Stattin EL, Emanuelsson M, Ehrencrona H, Rosenquist Brandell R, Dahl N.

Abstract

BACKGROUND:

Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2.

METHODS:

Three common SNPs in the gene, c.-77C>T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers.

RESULTS:

An association was observed between p.Arg280His-rs25489 and breast cancer risk for BRCA2 mutation carriers, with rare homozygotes at increased risk relative to common homozygotes (hazard ratio: 22.3, 95% confidence interval: 14.3-34, P<0.001). This association was further tested in a second series of 4480 BRCA1 and 3016 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2.

CONCLUSIONS AND INTERPRETATION:

No evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers.

PMID:
21427728
[PubMed - indexed for MEDLINE]
PMCID:
PMC3078599
Free PMC Article
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