Cancer Epidemiol Biomarkers Prev  2000 Oct;9(10):1027-35 

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

Behrens C, Travis LB, Wistuba II, Davis S, Maitra A, Clarke EA, Lynch CF,
Glimelius B, Wiklund T, Tarone R, Gazdar AF.

Hamon Center for Therapeutic Oncology Research University of Texas Southwestern
Medical Center, Dallas 75390-8593, USA.

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.

PMID: 11045784 [PubMed - indexed for MEDLINE]