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Age-associated gene expression in normal breast tissue mirrors qualitative age-at-incidence patterns for breast cancer.

ABSTRACT: Age is the strongest breast cancer risk factor, with overall breast cancer risk increasing steadily beginning at approximately 30 years of age. However, while breast cancer risk is lower among younger women, young women's breast cancer may be more aggressive. Although, several genomic and epidemiologic studies have shown higher prevalence of aggressive, estrogen-receptor negative breast cancer in younger women, the age-related gene expression that predisposes to these tumors is poorly understood. Characterizing age-related patterns of gene expression in normal breast tissues may provide insights on etiology of distinct breast cancer subtypes that arise from these tissues.To identify age-related changes in normal breast tissue, 96 tissue specimens from patients with reduction mammoplasty, ages 14 to 70 years, were assayed by gene expression microarray.Significant associations between gene expression levels and age were identified for 802 probes (481 increased, 321 decreased with increasing age). Enriched functions included "aging of cells," "shape change," and "chemotaxis," and enriched pathways included Wnt/beta-catenin signaling, Ephrin receptor signaling, and JAK/Stat signaling. Applying the age-associated genes to publicly available tumor datasets, the age-associated pathways defined two groups of tumors with distinct survival.The hazard rates of young-like tumors mirrored that of high-grade tumors in the Surveillance, Epidemiology, and End Results Program, providing a biologic link between normal aging and age-related tumor aggressiveness.These data show that studies of normal tissue gene expression can yield important insights about the pathways and biologic pressures that are relevant during tumor etiology and progression.

SUBMITTER: Pirone JR

PROVIDER: S-EPMC3684707 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Age-associated gene expression in normal breast tissue mirrors qualitative age-at-incidence patterns for breast cancer.

Pirone Jason R JR D'Arcy Monica M Stewart Delisha A DA Hines William C WC Johnson Melissa M Gould Michael N MN Yaswen Paul P Jerry D Joseph DJ Smith Schneider Sallie S Troester Melissa A MA

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20120802 10

<h4>Background</h4>Age is the strongest breast cancer risk factor, with overall breast cancer risk increasing steadily beginning at approximately 30 years of age. However, while breast cancer risk is lower among younger women, young women's breast cancer may be more aggressive. Although, several genomic and epidemiologic studies have shown higher prevalence of aggressive, estrogen-receptor negative breast cancer in younger women, the age-related gene expression that predisposes to these tumors i ...[more]

PMID: 22859400

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Age-associated gene expression in normal breast tissue mirrors qualitative age-at-incidence patterns for breast cancer.

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Age-associated gene expression in normal breast tissue mirrors qualitative age-at-incidence patterns for breast cancer.

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