Associated cancers in Waldenström macroglobulinemia: clues for common genetic predisposition.
BACKGROUND
Several population-based and cohort studies have reported an increased risk of second cancers in lymphoproliferative disorders (LPDs). The cause of second cancers in LPDs is probably multifactorial, and the relative contribution of treatments, genetic predisposition, and immune dysfunction typical of LPDs is still unclear.


METHODS
We retrospectively studied 230 patients with Waldenström macroglobulinemia (WM) to assess the frequency, characteristics, and predictive factors of second cancers and to evaluate whether patients with WM are at higher risk of second cancers compared with an age- and sex-matched control population.


RESULTS
In a competing-risk model, the cumulative incidence of solid cancers was 6% at 5 years, 11% at 10 years, and 17% at 15 years, whereas the incidence of hematologic malignancies was 4% at 5 years, 7% at 10 years, and 8% at 15 years. Compared with an age- and sex-matched population, the overall risk of second cancers was 1.7-fold higher than expected (95% confidence interval [CI], 1.22-2.38; P = .002). Patients with WM were at increased risk for diffuse large B-cell lymphoma (DLBCL) (standardized incidence ratio [SIR], 8.64; 95% CI, 3.88-19.22; P < .0001), myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) (SIR 9.5; 95% CI, 3.6-25.3; P < .0001), and brain cancer (SIR, 7.59; 95% CI, 1.9-30.4; P < .0001). The risk of a second hematologic malignancy was 5-fold higher in treated than in untreated patients (P = .08).


CONCLUSIONS
Patients with WM are at increased risk of DLBCL, MDS/AML, and brain cancers compared with the general population. Further studies are needed to clarify whether the increased incidence of second cancers is related to treatments, to the immunologic impairment associated with the disease, or to genetic predisposition.
Division of Hematology, Niguarda Ca' Granda Hospital, Milano, Italy.
Enrica
E
Morra
Marzia
M
Varettoni
Alessandra
A
Tedeschi
Luca
L
Arcaini
Francesca
F
Ricci
Cristiana
C
Pascutto
Sara
S
Rattotti
Eleonora
E
Vismara
Laura
L
Paris
Mario
M
Cazzola
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000209:etiology*; D012189:Retrospective Studies; D012306:Risk; D008258:Waldenstrom Macroglobulinemia / Q000150:complications* / Q000188:drug therapy / Q000235:genetics*; D057832:Watchful Waiting
Hematologic malignancies; Second cancers; Solid tumors; Waldenström macroglobulinemia