Genetic variants in FGFR2 and MAP3K1 are associated with the risk of familial and early-onset breast cancer in a South-American population
Author
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Jara Sosa, Lilian
Author
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González Hormazábal, Patricio
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Author
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Cerceño, Kerube
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Author
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Di Capua, Gabriella A.
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Author
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Reyes, José M.
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Author
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Blanco Castillo, Rafael
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Author
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Bravo, Teresa
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Author
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Peralta Musre, Octavio
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Author
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Gómez, Fernando
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Author
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Waugh, Enrique
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Margarit, Sonia
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Author
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Gladys, Ibáñez
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Author
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Romero Osses, Carmen
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Author
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Pakomio, Janara
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Author
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Roizen, Gigia
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Admission date
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2014-01-27T20:35:14Z
Available date
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2014-01-27T20:35:14Z
Publication date
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2012-12-07
Cita de ítem
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Breast Cancer Res Treat (2013) 137:559–569
en_US
Identifier
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DOI 10.1007/s10549-012-2359-z
Identifier
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https://repositorio.uchile.cl/handle/2250/129187
General note
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Artículo de publicación ISI.
en_US
Abstract
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Genome-Wide Association Studies have
identified several loci associated with breast cancer (BC) in
populations of different ethnic origins. One of the strongest
associations was found in the FGFR2 gene, and MAP3K1
has been proposed as a low-penetrance BC risk factor. In
this study, we evaluated the associations among FGFR2
SNPs rs2981582, rs2420946, and rs1219648; and MAP3K1
rs889312, with BC risk in 351 BRCA1/2-negative Chilean
BC cases and 802 controls. All the SNPs studied were
significantly associated with increased BC risk in familial
BC and in non-familial early-onset BC, in a dose-dependent
manner. Subjects with 3 risk alleles were at a significantly
increased risk of BC compared with subjects with
0–2 risk alleles, in both familial BC and early-onset nonfamilial
BC (OR = 1.47, 95 % CI 1.04–2.07, P = 0.026
and OR = 2.04 95 % CI 1.32–3.24, P\0.001, respectively).
In the haplotype analysis, the FGFR2 rs2981582
T / rs2420946 T / rs1219648 G haplotype (ht2) was associated
with a significantly increased BC risk compared with
the rs2981582 C / rs2420946 C / rs1219648 A haplotype
in familial BC and in non-familial early-onset BC (OR =
1.32, 95 % CI 1.06–1.65, P = 0.012; OR = 1.46, 95 % CI
1.11–1.91, P = 0.004, respectively). When the FGFR2 ht2
and MAP3K1 rs889312 were evaluated as risk alleles, the
risk of BC increased in a dose-dependent manner as
the number of risk alleles increased (P trend \0.0001),
indicating an additive effect. Nevertheless, there is no
evidence of an interaction between FGFR2 ht2 and the
MAP3K1 rs889312 C allele. These findings suggest that
genetic variants in the FGFR2 and MAP3K1 genes may
contribute to genetic susceptibility to BC.
en_US
Patrocinador
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Authors
received the grant sponsor from Fondo Nacional de Desarrollo
Cientı´fico y Tecnolo´gico (FONDECYT)/Corporacio´n Nacional del
Ca´ncer. Grant number: 1110081.