To the editor:

We read with interest the article by Frederiksen et al about the increased risk of developing hematologic and nonhematologic cancers in a large cohort of Danish patients with myeloproliferative neoplasms (MPNs).1  In a previous study2  we reported that MPN patients have a 3.44-fold higher risk of lymphoid neoplasms compared with the general population, in line with current1  and other results.3  Considering nonhematologic cancers, Frederiksen et al reported a standardized incidence ratio (SIR) value of 1.2 (95% CI: 1.0-1.4) for essential thrombocythemia (ET) and 1.4 (95% CI: 1.3-1.5) for polycythemia vera (PV).1  These estimates were based on 1578 ET and 4625 PV patients after a median follow-up of 4.0 and 5.0 years, respectively.

We have followed a series of 733 MPN patients, 302 PV, 375 ET, and 56 primary myelofibrosis, consecutively diagnosed at the Hematology Section, University of Florence, from 1980 to 2006, all under an active clinical follow-up protocol and residing in a defined area of Tuscany, central Italy. The identification of cancer cases was obtained through individual chart records and linkages with the hospital discharge system, pathology department registries, Regional Cancer Registry, local town offices, and Regional Mortality Registry. For each subject, the period at risk started from the date of MPN diagnosis to the date of diagnosis of subsequent primary cancer, death, or December 31, 2006 (end of follow-up), whichever came first. The mean follow-up period was 6.45 years with a total of 4724.72 person-years. The specific cancer incidence rates in the general population were provided by the Tuscany Cancer Registry, which is active in the same area since 1984 and involves 1 161 000 inhabitants; SIRs were calculated as the ratio of observed to expected cases. The study was conducted in accordance with institutional guidelines after approval by local ethics committee.

Results showed the absence of a specific pattern of risk of cancer of all sites (SIR = 0.87, 95% CI: 0.64, 1.14) except for melanoma cases for which we found a significantly elevated risk compared with the general population (SIR = 3.69, 95% CI: 1.39, 9.64; Table 1); however, because of the low number of cases (2 PV, 1 ET, and 1 myelofibrosis) such an association remains to be validated. The analyses stratified by sex (361 males/372 females), JAK2V617F mutational status (340 JAK2V617F mutated/137 wild-type), and cytotoxic therapy with hydroxyurea (59.6% of 659 evaluated) did not show any specific risk pattern (not shown in detail).

Table 1

Nonhematologic cancer incidence in 733 MPN patients, overall and by specific site*; number of observed and expected cases, relative risks as estimated by standardized incidence ratios (SIR) and 95% confidence intervals (1980-2006 period).

Any MPNCancer siteICD IXObservedExpectedSIR§95% CI
 Digestive system 150-159 10 15.08 0.63 0.33-1.16 
     Stomach 151 3.41 1.11 0.42-2.85 
     Colon & Rectum 153-154 7.75 0.61 0.25-1.46 
 Respiratory system 160-165 7.73 0.86 0.41-1.80 
     Lung 162 6.68 0.85 0.38-1.90 
 Melanoma 172 1.03 3.69 1.39-9.64 
 Skin (non-melanoma) 173 9.06 1.03 0.56-1.92 
 Breast 174 5.96 0.79 0.33-1.90 
 Prostate 185 5.56 0.68 0.25-1.80 
 Bladder 188 2.46 1.15 0.37-3.58 
 Kidney and other urinary organs 189 1.67 1.12 0.28-4.48 
 All cancer sites 140-199 49 56.62 0.87 0.64-1.14 
Any MPNCancer siteICD IXObservedExpectedSIR§95% CI
 Digestive system 150-159 10 15.08 0.63 0.33-1.16 
     Stomach 151 3.41 1.11 0.42-2.85 
     Colon & Rectum 153-154 7.75 0.61 0.25-1.46 
 Respiratory system 160-165 7.73 0.86 0.41-1.80 
     Lung 162 6.68 0.85 0.38-1.90 
 Melanoma 172 1.03 3.69 1.39-9.64 
 Skin (non-melanoma) 173 9.06 1.03 0.56-1.92 
 Breast 174 5.96 0.79 0.33-1.90 
 Prostate 185 5.56 0.68 0.25-1.80 
 Bladder 188 2.46 1.15 0.37-3.58 
 Kidney and other urinary organs 189 1.67 1.12 0.28-4.48 
 All cancer sites 140-199 49 56.62 0.87 0.64-1.14 
PVCancer siteICD IXObservedExpectedSIR§95% CI
 Digestive system 150-159 7.26 0.83 0.37-1.84 
     Colon & Rectum 153-154 3.70 1.08 0.41-2.88 
 Respiratory system 160-165 4.23 0.71 0.23-2.20 
     Lung 162 3.63 0.83 0.27-2.56 
 Melanoma 172 0.47 4.26 1.06-17.04 
 Skin (non-melanoma) 173 4.33 1.38 0.62-3.08 
 Prostate 185 3.18 0.63 0.16-2.52 
 Bladder 188 1.33 2.25 0.73-6.98 
 Kidney and other urinary organs 189 0.68 2.96 0.74-11.84 
 All cancer sites 140-199 26 26.98 0.96 0.63-1.41 
PVCancer siteICD IXObservedExpectedSIR§95% CI
 Digestive system 150-159 7.26 0.83 0.37-1.84 
     Colon & Rectum 153-154 3.70 1.08 0.41-2.88 
 Respiratory system 160-165 4.23 0.71 0.23-2.20 
     Lung 162 3.63 0.83 0.27-2.56 
 Melanoma 172 0.47 4.26 1.06-17.04 
 Skin (non-melanoma) 173 4.33 1.38 0.62-3.08 
 Prostate 185 3.18 0.63 0.16-2.52 
 Bladder 188 1.33 2.25 0.73-6.98 
 Kidney and other urinary organs 189 0.68 2.96 0.74-11.84 
 All cancer sites 140-199 26 26.98 0.96 0.63-1.41 
ETCancer siteICD IXObservedExpectedSIR§95% CI
 Digestive system 150-159 6.90 0.43 0.14-1.35 
     Stomach 151 1.53 1.30 0.33-5.23 
 Respiratory system 160-165 2.91 1.37 0.52-3.66 
     Lung 162 2.54 1.18 0.38-3.67 
 Skin (non-melanoma) 173 4.14 0.72 0.23-2.25 
 Breast 174 3.95 1.26 0.52-3.04 
 Prostate 185 1.85 1.08 0.27-4.33 
 All cancer sites 140-199 22 26.22 0.84 0.53-1.27 
ETCancer siteICD IXObservedExpectedSIR§95% CI
 Digestive system 150-159 6.90 0.43 0.14-1.35 
     Stomach 151 1.53 1.30 0.33-5.23 
 Respiratory system 160-165 2.91 1.37 0.52-3.66 
     Lung 162 2.54 1.18 0.38-3.67 
 Skin (non-melanoma) 173 4.14 0.72 0.23-2.25 
 Breast 174 3.95 1.26 0.52-3.04 
 Prostate 185 1.85 1.08 0.27-4.33 
 All cancer sites 140-199 22 26.22 0.84 0.53-1.27 
*

Only cancer sites with at least 2 observed cases.

Cases of cancer newly diagnosed in MPN patients.

Expected cases of cancer according to incidence rates in the general population of the area applied to the number of person years in the study follow up.

§

Standardized incidence ratio, obtained from the ratio of Observed to Expected cases ‖ except lymphoproliferative neoplasm

Our study is based on a smaller population compared with Frederiksen et al1  and has the advantages of a slightly longer follow-up and of being conducted in a narrower area with an active local registry. Our carefully controlled patient series reduces the risk of possible misclassification at baseline, potentially present in a very large series obtained in a country-wide study, as mentioned by the authors.1  In any case, we believe that the low SIR value (1.2 to 1.4) found in the Danish study,1  together with our negative results, should call for much caution before accepting d'emblée the idea that the incidence of nonhematologic cancers is specifically increased in MPNs and, even more, before discussing such topic with the patients.

Acknowledgments: The study was funded by a grant from Associazione Italiana per la Ricerca sul Cancro (AIRC, Milano) “Special Program Molecular Clinical Oncology 5 × 1000” to AGIMM (AIRC-Gruppo Italiano Malattie Mieloproliferative), project number 1005. A detailed description of the AGIMM project is available at http://www.progettoagimm.it. The support of Fondazione A. Pofferi, Pistoia, is also acknowledged.

Contribution: M.C.S. performed research, analyzed data, and contributed to manuscript writing; G.M. analyzed data and contributed to manuscript writing; E.A., L.P., P.G., D.P., A.B. performed research; and A.M.V. designed research, analyzed data, and wrote the manuscript.

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Alessandro M. Vannucchi, MD, Section of Hematology, Department of Critical Care, University of Florence, Largo Brambilla 3, 50134 Florence, Italy; e-mail: amvannucchi@unifi.it.

1
Frederiksen
 
H
Farkas
 
DK
Christiansen
 
CF
Hasselbalch
 
HC
Sørensen
 
HT
Chronic myeloproliferative neoplasms and subsequent cancer risk: a Danish population-based cohort study.
Blood
2011
, vol. 
118
 
25
(pg. 
6515
-
6520
)
2
Vannucchi
 
AM
Masala
 
G
Antonioli
 
E
, et al. 
Increased risk of lymphoid neoplasms in patients with Philadelphia chromosome-negative myeloproliferative neoplasms.
Cancer Epidemiol Biomarkers Prev
2009
, vol. 
18
 
7
(pg. 
2068
-
2073
)
3
Rumi
 
E
Passamonti
 
F
Elena
 
C
, et al. 
Increased risk of lymphoid neoplasm in patients with myeloproliferative neoplasm: a study of 1915 patients.
Haematologica
2011
, vol. 
96
 
3
(pg. 
454
-
458
)

Sign in via your Institution