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8q24 Cancer risk allele associated with major metastatic risk in inflammatory breast cancer.

ABSTRACT: BACKGROUND: Association studies have identified low penetrance alleles that participate to the risk of cancer development. The 8q24 chromosomal region contains several such loci involved in various cancers that have been recently studied for their propensity to influence the clinical outcome of prostate cancer. We investigated here two 8q24 breast and colon cancer risk alleles in the close vicinity of the MYC gene for their role in the occurrence of distant metastases. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective series of 449 patients affected with breast or colon adenocarcinoma was genotyped for the rs13281615 and/or rs6983267 SNPs. Statistical analyses were done using the survival package v2.30 in the R software v2.9.1. The two SNPs did not influence the development of distant metastases of colon cancer; rs6983267 showed a mild effect on breast cancer. However, this effect was greatly emphasized when considering inflammatory breast cancer (IBC) solely. Replicated on a larger and independent series of IBC the contribution of the genotype to the metastatic risk of IBC was found an independent predictor of outcome (p = 2e-4; OR 8.3, CI95:2.6-33). CONCLUSIONS/SIGNIFICANCE: Our study shows first that the monitoring of this specific germline variation may add a substantial tool for IBC prognostication, an aggressive disease that evolves towards distant metastases much more frequently than non-IBC and for which no reliable prognostic factor is available in medical practice. Second, it more generally suggests that risk alleles, while associated with low susceptibility, could correlate with a high risk of metastasis.

SUBMITTER: Bertucci F

PROVIDER: S-EPMC3362533 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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8q24 Cancer risk allele associated with major metastatic risk in inflammatory breast cancer.

Bertucci François F Lagarde Arnaud A Ferrari Anthony A Finetti Pascal P Charafe-Jauffret Emmanuelle E Van Laere Steven S Adelaide José J Viens Patrice P Thomas Gilles G Birnbaum Daniel D Olschwang Sylviane S

PloS one 20120529 5

<h4>Background</h4>Association studies have identified low penetrance alleles that participate to the risk of cancer development. The 8q24 chromosomal region contains several such loci involved in various cancers that have been recently studied for their propensity to influence the clinical outcome of prostate cancer. We investigated here two 8q24 breast and colon cancer risk alleles in the close vicinity of the MYC gene for their role in the occurrence of distant metastases.<h4>Methodology/prin ...[more]

PMID: 22666420

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Project description:IntroductionAltered serum microRNA (miRNA) levels may be correlated with a dysregulated expression pattern in parental tumor tissue and reflect the clinical evolution of disease. The overexpression of miR-21, miR-10b, and miR-19a is associated with the acquisition of malignant characteristics (increased tumor cell proliferation, migration, invasion, dissemination, and metastasis); thus, we determined their utility as serum biomarkers for aggressive breast cancer (HER2-overexpressed or -amplified [HER2(+)] and inflammatory breast cancer [IBC]).Experimental designIn this prospective study, we measured miR-21, miR-10b, and miR-19a levels using quantitative reverse transcriptase-polymerase chain reaction in the serum of 113 breast cancer patients and determined their association with clinicopathologic factors and clinical outcome. Thirty healthy donors with no history of cancer were enrolled as controls.ResultsPatients with non-metastatic HER2(+) breast cancer had higher serum miR-21 median levels than patients with non-metastatic HER2(-) disease (p?=?0.044); whereas patients with metastatic HER2(+) breast cancer had higher serum miR-10b median levels than patients with metastatic HER2(-) disease (p?=?0.0004). There were no significant differences in serum miR-19a median levels between HER2(+) and HER2(-) groups, regardless of the presence of metastases. High serum miR-19a levels were associated with IBC (p?=?0.039). Patients with metastatic IBC had significantly higher serum miR-19a median levels than patients with metastatic non-IBC (p?=?0.019). Finally, high serum miR-19a levels were associated with longer progression-free survival time (10.3 vs. 3.2 months; p?=?0.022) and longer overall survival time (median not reached vs. 11.2 months; p?=?0.003) in patients with metastatic HER2(+) IBC.ConclusionHigh levels of miR-21 and miR-10b were present in the serum of patients with non-metastatic and metastatic HER2(+) breast cancer, respectively. High levels of serum miR-19a may represent a biomarker for IBC that is predictive for favorable clinical outcome in patients with metastatic HER2(+) IBC.

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8q24 Cancer risk allele associated with major metastatic risk in inflammatory breast cancer.

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8q24 Cancer risk allele associated with major metastatic risk in inflammatory breast cancer.

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