Rare variants of ATM and risk for Hodgkin's disease and radiation-associated breast cancers Journal Article

Authors: Offit, K.; Gilad, S.; Paglin, S.; Kolachana, P.; Roisman, L. C.; Nafa, K.; Yeugelowitz, V.; Gonzales, M.; Robson, M.; McDermott, D.; Pierce, H. H.; Kauff, N. D.; Einat, P.; Jhanwar, S.; Satagopan, J. M.; Oddoux, C.; Ellis, N.; Skaliter, R.; Yahalom, J.
Article Title: Rare variants of ATM and risk for Hodgkin's disease and radiation-associated breast cancers
Abstract: Purpose: In this study, we first sought to evaluate whether individuals heterozygous for ATM mutations may have an increased susceptibility to radiation-induced breast cancer (BC) after treatment for Hodgkin's disease (HD). We next sought to determine the frequency of ATM variants in patients with Hodgkin's lymphoma, regardless of coexisting BC, compared with healthy volunteers. Experimental Design: Full sequence analysis of ATM was performed on cDNA from peripheral blood lymphocytes from 37 cases of BC after therapeutic radiation therapy for HD and 27 comparison cases with HD and no BC treated during the same time period. The frequency of ATM variants was analyzed in the total group of 64 cases of HD and compared to allele frequencies in 128 ethnically matched controls from the same geographical region. Results: No protein-truncating ATM mutations were observed in cases with HD with or without BC. Missense mutations were more frequent in the cohort with HD compared with patients with BC following HD (P = 0.02). The median time from HD to the development of BC was 18 years in patients with ATM variants compared with 16 years in those with no ATM variants (P = 0.04). Multiple ATM variants, including one homozygous mutation, were observed in 9 HD cases. Conclusions: Heterozygous protein-truncating or missense mutations of ATM were not associated with increased radiation-associated risk of BC after HD. The observation of multiple germ-line mutations and a homozygote suggests that rare ATM variants may constitute cancer-susceptibility alleles in a subset of cases.
Keywords: adolescent; adult; child; clinical article; controlled study; aged; gene mutation; sequence analysis; missense mutation; mutation; case-control studies; dna-binding proteins; exons; cell cycle proteins; allele; gene; cells, cultured; cancer susceptibility; cohort studies; breast cancer; radiation; gene frequency; breast neoplasms; hodgkin disease; germ line; protein-serine-threonine kinases; neoplasms, radiation-induced; tumor suppressor proteins; homozygote; radiation hazard; lymphocyte; lymphocytes; rna, neoplasm; geography; dna, complementary; atm gene; humans; human; male; female; priority journal; article
Journal Title: Clinical Cancer Research
Volume: 8
Issue: 12
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2002-12-01
Start Page: 3813
End Page: 3819
Language: English
PUBMED: 12473594
PROVIDER: scopus
Notes: Export Date: 14 November 2014 -- Source: Scopus