Breast cancer genetic risk profile is differentially associated with interval and screen-detected breast cancers.
Ann Oncol
; 26(3): 517-22, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25488685
ABSTRACT
BACKGROUND:
Polygenic risk profiles computed from multiple common susceptibility alleles for breast cancer have been shown to identify women at different levels of breast cancer risk. We evaluated whether this genetic risk stratification can also be applied to discriminate between screen-detected and interval cancers, which are usually associated with clinicopathological and survival differences. PATIENTS ANDMETHODS:
A 77 single-nucleotide polymorphism polygenic risk score (PRS) was constructed for breast cancer overall and by estrogen receptor (ER) status. PRS was inspected as a continuous (per standard deviation increment) variable in a case-only design. Modification of the PRS by mammographic density was evaluated by fitting an additional interaction term.RESULTS:
PRS weighted by breast cancer overall estimates was found to be differentially associated with 1865 screen-detected and 782 interval cancers in the LIBRO-1 study {age-adjusted odds ratio (OR)perSD [95% confidence interval (CI)] 0.91 [0.83-0.99], P = 0.023}. The association was found to be more significant for PRS weighted by ER-positive breast cancer estimates [ORperSD = 0.90 (0.82-0.98), P = 0.011]. This result was corroborated by two independent studies [combined ORperSD = 0.87 (0.76-1.00), P = 0.058] with no evidence of heterogeneity. When enriched for 'true' interval cancers among nondense breasts, the difference in the association with PRS in screen-detected and interval cancers became more pronounced [ORperSD = 0.74 (0.62-0.89), P = 0.001], with a significant interaction effect between PRS and mammographic density (Pinteraction = 0.017).CONCLUSION:
To our knowledge, this is the first report looking into the genetic differences between screen-detected and interval cancers. It is an affirmation that the two types of breast cancer may have unique underlying biology.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Mamografia
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Predisposição Genética para Doença
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Detecção Precoce de Câncer
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Transcriptoma
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article