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


RESULTS
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
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.
Centre de Recherche en Cancérologie de Marseille, Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France.
François
F
Bertucci
Arnaud
A
Lagarde
Anthony
A
Ferrari
Pascal
P
Finetti
Emmanuelle
E
Charafe-Jauffret
Steven
S
Van Laere
José
J
Adelaide
Patrice
P
Viens
Gilles
G
Thomas
Daniel
D
Birnbaum
Sylviane
S
Olschwang
D000483:Alleles; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D016019:Survival Analysis