Molecular changes in second primary lung and breast cancers after therapy for Hodgkin's disease

C. Behrens, L. B. Travis, I. I. Wistuba, S. Davis, A. Maitra, E. A. Clarke, C. F. Lynch, B. Glimelius, T. Wiklund, R. Tarone, A. F. Gazdar

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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-βRII, 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.

Original languageEnglish (US)
Pages (from-to)1027-1035
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume9
Issue number10
StatePublished - 2000

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Second Primary Neoplasms
Hodgkin Disease
Lung Neoplasms
Breast Neoplasms
Microsatellite Repeats
Neoplasms
Minisatellite Repeats
Loss of Heterozygosity
Therapeutics
Lung
Mutation
Frameshift Mutation
ras Genes
Genomic Instability
Immunosuppression
Breast
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Behrens, C., Travis, L. B., Wistuba, I. I., Davis, S., Maitra, A., Clarke, E. A., ... Gazdar, A. F. (2000). Molecular changes in second primary lung and breast cancers after therapy for Hodgkin's disease. Cancer Epidemiology Biomarkers and Prevention, 9(10), 1027-1035.

Molecular changes in second primary lung and breast cancers after therapy for Hodgkin's disease. / Behrens, C.; Travis, L. B.; Wistuba, I. I.; Davis, S.; Maitra, A.; Clarke, E. A.; Lynch, C. F.; Glimelius, B.; Wiklund, T.; Tarone, R.; Gazdar, A. F.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 9, No. 10, 2000, p. 1027-1035.

Research output: Contribution to journalArticle

Behrens, C, Travis, LB, Wistuba, II, Davis, S, Maitra, A, Clarke, EA, Lynch, CF, Glimelius, B, Wiklund, T, Tarone, R & Gazdar, AF 2000, 'Molecular changes in second primary lung and breast cancers after therapy for Hodgkin's disease', Cancer Epidemiology Biomarkers and Prevention, vol. 9, no. 10, pp. 1027-1035.
Behrens C, Travis LB, Wistuba II, Davis S, Maitra A, Clarke EA et al. Molecular changes in second primary lung and breast cancers after therapy for Hodgkin's disease. Cancer Epidemiology Biomarkers and Prevention. 2000;9(10):1027-1035.
Behrens, C. ; Travis, L. B. ; Wistuba, I. I. ; Davis, S. ; Maitra, A. ; Clarke, E. A. ; Lynch, C. F. ; Glimelius, B. ; Wiklund, T. ; Tarone, R. ; Gazdar, A. F. / Molecular changes in second primary lung and breast cancers after therapy for Hodgkin's disease. In: Cancer Epidemiology Biomarkers and Prevention. 2000 ; Vol. 9, No. 10. pp. 1027-1035.
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