Premium
Loss of heterozygosity at 11q23.1 and survival in breast cancer: Results of a large European study
Author(s) -
Laake Kirsten,
Laun Virpi,
Niederacher Dieter,
Gudlaugsdottir Sigfridur,
Seitz Susanne,
Rio Pascale,
Champème MarieHélène,
Bièche Ivan,
Birnbaum Daniel,
White Gavin,
Sztan Marianna,
Sever Natasa,
Plummer Sarah,
Osorio Ana,
Broeks Annegien,
Huusko Pia,
Spurr Nigel,
Borg Åke,
CletonJansen AnneMarie,
Veer Laura van't,
Benitez Javier,
Casey Graham,
Peterlin Borut,
Olah Edith,
Varley Jenny,
Big YvesJean,
Scherneck Siegfried,
Sigurdardottir Valgerdur,
Lidereau Rosette,
Eyfjord Jorunn,
Beckmann Matthias Wilhelm,
Winqvist Robert,
Skovlund Eva,
BørresenDale AnneLise
Publication year - 1999
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(199907)25:3<212::aid-gcc3>3.0.co;2-g
Subject(s) - loss of heterozygosity , breast cancer , biology , cancer research , candidate gene , cancer , ataxia telangiectasia , hazard ratio , oncology , gene , genetics , medicine , allele , dna , confidence interval , dna damage
Among the chromosomal regions commonly undergoing deletions in breast tumors is 11q23.1. The genes that are targets for loss of heterozygosity (LOH) in this region is not yet established. One of the candidate genes located in this region is ATM , responsible for the rare autosomal recessive disorder ataxia‐telangiectasia (A‐T). Interestingly, A‐T heterozygotes may have an increased risk of cancer, in particular breast cancer, although this is still controversial. A common assumption has been that the target for the LOH at 11q23.1 in breast carcinoma is the ATM gene, but the area studied has been too large, the density of markers too low, and the number of tumors studied has been too small to draw any firm conclusions. The present study is a multicenter study including 918 breast cancer patients with clinical information and survival data available for most of them. Primary breast tumors were investigated for LOH using a high density of microsatellite markers spanning approximately 6 Mb around the ATM gene. Survival analyses showed that there are most likely one or more candidate genes in a 3–4 Mb region between the markers D11S1819 and D11S927 including the ATM gene. Cancer‐specific survival was significantly reduced in patients whose tumors exhibited LOH of markers D11S2179 (within the ATM gene), D11S1778 , D11S1294 , and D11S1818 . The highest survival hazard ratios were 1.8 (CI 1.2–2.8, P = 0.010) and 2.1 (CI 1.4–3.0, P = 0.0004) for markers D11S2179 and D11S1818 , respectively. One or more of these markers are therefore most likely to be located close to or within genes associated with breast cancer survival. Genes Chromosomes Cancer 25:212–221, 1999. © 1999 Wiley‐Liss, Inc.