Journal article
Molecular changes in second primary lung and breast cancers after therapy for Hodgkin's disease
Cancer epidemiology, biomarkers & prevention, Vol.9(10), pp.1027-1035
2000
PMID: 11045784
Abstract
The risk of lung and breast cancer is significantly increased after therapy for Hodgkin's disease (HD), but there are few data that describe the molecular profiles of these tumors. We investigated the genetic abnormalities in second primary lung (n = 19) and breast cancers (n = 19) that follow therapy for HD ("post-HD cancers") and compared these with changes observed in corresponding tumor types (57 lung and 20 breast cancers) arising in the general population ("sporadic cancers"). DNA obtained from archival tissues was examined using PCR-based analyses for loss of heterozygosity and microsatellite alterations (MAs) at several chromosomal regions, TP53 and K-ras gene mutations, and frameshift mutations at minisatellite sequences at the coding regions of several genes (TGF-betaRII, IGFIIR, BAX, hMSH6, and hMSH3). The occurrence of loss of heterozygosity at all chromosomal regions taken together and frequencies at most individual areas were similar for the post-HD and sporadic cancers for both lung and breast sites. The overall frequency of MAs in the post-HD tumors was substantially greater (lung, 2.4-fold, P = 0.004; breast, 4.2-fold, P = 0.16) than that in the respective sporadic cancers. No differences in the pattern of TP53 and K-ras mutations were detected between post-HD and sporadic cancers. No mutations were detected at the minisatellite sequences examined. MAs, which reflect widespread genomic instability, occur at greatly increased frequency in post-HD lung and breast cancers. Although the mechanisms underlying the development of increased MAs are unknown, they have been associated with immunosuppression and radiation exposure. Future research should address the role that MAs, as well as other influences, may play in the development of neoplasias that occur after therapy for HD.
Details
- Title: Subtitle
- Molecular changes in second primary lung and breast cancers after therapy for Hodgkin's disease
- Creators
- Carmen Behrens - Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United StatesLois B Travis - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 209892, United StatesAdi F Gazdar - Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United StatesIgnacio I Wistuba - Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United StatesSamuel Davis - Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United StatesAnirban Maitra - Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United StatesE. Aileen Clarke - Cancer Care Ontario, Toronto, CanadaCharles F Lynch - Department of Preventive Medicine and Environmental Health, University of Iowa, Iowa City, Iowa 52242, United StatesBengt Glimelius - University Hospital, Uppsala S-751-75, SwedenTom Wiklund - Helsinki University Central Hospital, Helsinki, FinlandRobert Tarone - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 209892, United States
- Resource Type
- Journal article
- Publication Details
- Cancer epidemiology, biomarkers & prevention, Vol.9(10), pp.1027-1035
- Publisher
- American Association for Cancer Research
- PMID
- 11045784
- ISSN
- 1055-9965
- eISSN
- 1538-7755
- Language
- English
- Date published
- 2000
- Academic Unit
- Epidemiology
- Record Identifier
- 9984216738902771
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