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High Incidence of Myeloproliferative Disorders in Ashkenazi Jews in Northern Israel a

a

b

a

Y. Chaiter , B. Brenner , E. Aghai & I. Tatarsky a

Hematology Institute, Rambam Medical Center, Haifa, Israel

b

Hematology Institute Carmel Hospital, Haifa, Israel Published online: 01 Jun 2015.

To cite this article: Y. Chaiter, B. Brenner, E. Aghai & I. Tatarsky (1992) High Incidence of Myeloproliferative Disorders in Ashkenazi Jews in Northern Israel, Leukemia & Lymphoma, 7:3, 251-255 To link to this article: http://dx.doi.org/10.3109/10428199209053630

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Leukemia and Lymphoma, Vol. I , pp. 251-255

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High Incidence of Myeloproliferative Disorders in Ashkenazi Jews in Northern Israel Y. CHAITER', B. BRENNER', E. AGHAI', and I. TATARSKY'

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Hematology Institute, Rambam Medical Center', and Hematology Institute Carmel Hospitalz, Haifa, Israel (Received 18 December 1991)

We have analysed epidemiological parameters in 339 patients with myeloproliferative disorders (MPD) diagnosed in northern Israel between 1975 and 1989 as having polycythemia Vera (191 patients), agnogenic myeloid metaplasia (AMM) (1 13) and essential thrombocythemia (ET) (36). Mean average annual incidence was 11.4 per 1 million residents for polycythemia Vera, 6.5 for AMM and 2.1 for ET. For all three diseases the average annual incidence increased with age and was 10 times higher in patients over 65 years compared to those less under the age of 45 years. Four percent of all patients had relatives with MPD. Incidence of M P D in Jews was 10 fold higher than expected compared to Arabs and this difference was noted for all 3 diseases. The incidence in Ashkenazi Jews originating from eastern and central Europe, was 10 and 20 folds higher than in Sephardic Jews and Arabs respectively. Mean age at diagnosis of M P D in Arabs and Sephardic Jews was lower than in Ashkenazi Jews (52 and 56 years compared to 64 years P < 0.05). Likewise, mean age at diagnosis was lower in the 11.5% of M P D patients with prior exposure to biological or chemical hazards compared to unexposed individuals (58 years versus 63 years, P < 0.02). These data demonstrate a cluster of M P D in Ashkenazi Jews in northern Israel and emphasize the importance of genetic predisposition possibly interacting with acquired factors in the pathogenesis of these disorders. KEY WORDS:

Myeloproliferative disorders polycythemia Vera metaplasia thrombocythemia

agnogenic myeloid

incidence ranging from 0.2 to 13.2 cases per 1,000,000 residents4-*. Furthermore, an increased prevalence of The myeloproliferative disorders (MPD) are a group MPD has been found in relatives of patients with of clonal diseases manifested by abnormal prolifera- polycythemia Vera and in patients with Jewish .". epidemiological data is availtion of one or more hemopoietic cell lines. While the a n c e ~ t r y ~ ~ ~Limited clinical manifestations, course and prognosis of MPD able on agnogenic myeloid metaplasia (AMM)' and are well described, the etiology of these disorders has almost no studies have been reported on the average not been elucidated lP3. Previous epidemiological annual incidence of essential thrombocythemia (ET). studies on patients with polycythemia Vera, reported In the present study we report the epidemiological from different areas, have suggested an average annual data of 339 M P D patients from northern Israel. Since Israel has absorbed Jewish immigrants from different parts of the world, but also has a large Arab population, we had the opportunity to analyse the Address for correspondence: B. Brenner M.D., Department of Hematology, Rambam Medical Center, P.O. Box 9602, Haifa, effect of ethnicity besides age, sex and residence area, 31096, Israel. on the prevalence of MPD in a large group of patients.

INTRODUCTION

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Y. CHAITER, el a/.

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PATIENTS AND METHODS

Statistical analysis

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Patients The study population included all patients diagnosed as having polycythemia Vera, AMM or ET between 1975 to 1989 in the 4 major medical centers of northern Israel: Rambam medical center, BneiZion medical center and Carmel hospital (Haifa) and Haemek medical center (Afula). The total number of patients was 339 and included 191 patients with polycythemia Vera, 112 with AMM and 36 with ET. The diagnosis of polycythemia Vera was based on the criteria of the polycythemia Vera study group”. Category A criteria included: A , - Red cell mass > 36 ml/kg Male; 32 ml/kg Female; A, - 0,saturation >%!YO; A, - splenomegaly. Diagnosis of polycythemia Vera required presence of all 3 category A parameters or the presence of A, + A, plus any 2 parameters of category B (platelet count >400,00O/p1; leukocytes > 12,00O/pI; LAP score > 100; B,, > 900 pg/ml. Criteria for diagnosis of AMM included: Hepatosplenomegaly, extra medullary hematopoiesis, leukoerythroblastic blood picture with tear-drop poikylocytosis, and bone marrow f i b r o s i ~ ’ Diagnosis ~. of ET required: Repeated platelet counts > 1,000,000 per pl, megakaryocyte hyperplasia in bone marrow, normal red blood cell mass and no evidence for secondary thromb~cytosis’~. Epidemiological data on each patient included age at diagnosis, sex, ethnicity subgrouped as follows: Ashkenazi Jews (migrants from Europe, America or Oceania, Sephardic Jews (migrants of Asia, Africa, Greece and Bulgaria) and Arabs, country of origin and residence area-urban ( > 10,000 inhabitants) or rural. Prior exposure to biological or chemical hazards, and presence of MPD in relatives were also recorded.

The data was analyzed using a PC software. Statistical methods used included the X2 test, T-test, ANOVA and the Duncan test.”

RESULTS Of the 339 patients, 183 (53.5%) were males and 157 (46.5%) females with mean age at diagnosis not differing between sexes (62 and 63 years respectively). Likewise, mean age was similar in patients with Polycythemia Vera, AMM and ET. (62 k 13,62 f 14, 63 f 12 years respectively). The male female ratio was 1.22 in the Polycythemia Vera, 1.20 in the AMM and 0.71 in the ET group. The average annual incidence of all three MPD was 19.8 per 1,000,000 residents with a high incidence of Polycythemia Vera (11.14) and AMM (6.53) and a lower incidence of ET (2.10). In all three groups incidence correlated with increasing age with a 10 fold higher incidence in patients over 65 compared to patients under 45 years (Table 1). Of the 339 patients, 323 (95.3%), were Jews and only 16 were Arabs (4.7%). The observed ratio of Jews to Arabs -20 is substantially higher than the ratio in the population of northern Israel - 1.8(16) ( P < 0.0005). Analysis of the Jewish patients revealed a higher incidence in Ashkenazi Jews and a lower incidence in Sephardic Jews compared to their proportion in the population (Table 2). Mean age at diagnosis was lower in the Sephardic Jews and Arabs compared to Ashkenazi Jews (56, 52 and 64 years respectively, P < 0.05). While mean age of Polycythemia Vera patients was similar for both ethnic groups, Arabs with AMM were significantly younger than Jews ( P < 0.02). Average annual incidence of all three categories of MPD was 10 to 20 folds higher in Jews compared to Arabs (Figure 1, Table 3).

Table 1 Average annual age-specific incidence rates of myeloproliferative disorders per 1,OOO,OOO residents (Northern Israel 1975-1989)

Age group.!

P.V. E.T. A.M.M. Total

+

30-34

35-44

45-54

5544

65-74

75

2.47 1.64 0.82 4.93

6.61 1.10 4.95 12.66

15.84 3.17 10.29 29.30

46.75 9.52 26.84 83.12

81.56 11.82 43.74 137.12

51.87 13.45 36.50 101.83

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M P D IN NORTHERN ISRAEL Table 2 Percentage of ethnic groups in M P D patients compared to the general population of Northern Israel Ethnicity

Ashkenazi Jews Sephardic Jews Arabs Total

No. of MPD patients

Percent of’ MPD patients

Percent in population of Northern Israel

275 48 16 339

81.2 14.1 4.1 100

32.49 32.16 35.35 100.00

FREWMCY 120 100 80

60 40 20

0

- 29

35-44

45-54

55-64

65-74

75

t

ACE

Figure 2 Age specific average annual incidence of all 3 myeloproliferative disorders per 1,000,OOO residents (Northern Israel 1975-1989). Hatched bars = Ashkenazi Jews; White bars = Sephardic Jews; Black bars = Arabs.

FREQUENCY

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30-34

301

20

10

0

J

A

J

A

W

ET

AGN

J C I

Figure I Average annual ethnicity-specific incidence rates of myeloproliferative disorders per 1,OOO,OOO residents (Northern Israel 1975-1989). AGN = Agnogenic myeloid metaplasia; ET = Essential Thrombocythemia; PV = Polycythemia Vera; J = Jews: A = Arabs.

Analysis of country of origin revealed that 64% of all patients immigrated from Poland, USSR and Romania, with another 15% originating from central Europe (Germany, Austria, Hungary and Czekoslovakia). This prevalence is significantly higher than the prevalence of these subgroups in the general population of northern IsraelI6. A history of MPD in relatives was documented in 4.2% of Polycythemia Vera, 3.6% of AMM and 2.8% of ET patients. Examination of type of residence revealed higher incidence of all three M P D in urban patients compared to rural patients (Figure 3) with a total incidence of 24 compared to 11.5 per 1,000,000 residents. Prior exposure to biological or chemical hazards was documented in 11.5% of Polycythemia Vera, 8.9% of AMM and 16.7% of ET patients.

FREQUENCY Table 3 Average annual ethnicity-specific incidence rates of Myeloproliferative disorders per l,OOO,OOO residents (Northern Israel 1975-1989)

30 Ethnicity

P.V. E.T. A.M.M. Total

P

Jews

Arabs

20.25 3.85 11.44 35.54

1.30 0.19 1.48 2.96

I

20 O.oooO45 0.068 0.0056 0.0005

Examination of average annual incidence of M P D according to age and ethnicity revealed a very high incidence in Ashkenazi Jews over 55 years which was 10 folds and 20 folds higher than in Sephardic Jews and Arabs respectively (Figure 2).

10 ° L TOWN

V I LLffiE

Figure 3 Average annual incidence of myeloproliferative disorders per I,OOO,OOO residents according to type of residence (Northern Israel 1975-1989).

Y. CHAITER, et al.

254

Table 4 Reported average annual incidence of Polycythemia Vera per 1,000,000 residents Study location

No. of patients

Study period

Average annual incidence

Reference

Baltimore (USA) Israel Rochester (USA) Japan Birmingham (UK) Australia Finland England & Wales Israel

55 155 19 281 100 80 177 5528 191

195 1-60 1955-66 1935-69 1950-70 1935-70 196CL69 1968-76 1968-80 1975-89

5.0 7.8 22.2 0.2 5.1 13.2 5.4 8.1 11.1

Modan (1965) Modan (1971) Silverstein (1971) Kurita (1974) Waterhouse (1974) Dougan (1981) Matilla (1981) Prochazka (1986) Present Study

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Exposed patients were younger at diagnosis compared to unexposed individuals (58 vs 63 years P < 0.02).

Israel (-6.5 per l,OOO,OOO), with the incidence of AMM in Jews being 3 times higher than in a recent Australian report". The average annual incidence of ET in our patients was 2.1 per 1,000,000 residents and we were unable to find previous published data for DISCUSSION comparison of the incidence of this disease at the time The results of the present study shows a high average this report was prepared. Our results demonstrate a annual incidence of MPD in northern Israel. The low incidence of MPD in Arabs, which is similar to incidence of Polycythemia Vera - 11.4 per one million the low incidence reported from JapanI7. residents, is among the highest reported values (Table The extremely high ratio of Jews to Arabs in 4). Considering that studies of large number of Polycythemia Vera and AMM emphasizes the patients are more accurate, the incidence in the importance of genetic factors in the prevalence of present study is the highest among the different MPD. The more subtle differences observed between reports concerning over 100 Polycythemic patients. the incidence of MPD in urban and rural areas Furthermore, studies which had included patients suggest that acquired factors may be less important prior to 19604*s*9*17*'8 did not apply the criteria of that genetic factors. In fact while Jews largely reside the Polycythemia Vera study group and therefore may in urban areas, Arab residents in northern Israel more often live in rural areas. Thus, the difference between have overestimated the incidence of the disease. Our study suggests a slightly higher incidence of incidence in rural and urban residence may solely Polycythemia Vera and AMM in males which is in result from differences in population ethnicity. accordance with previously reported data6-I9. Our Although M P D are less common in Sephardic Jews data also suggest a higher incidence of all three MPD and Arabs, age at diagnosis in these ethnic groups is with increasing age reaching a peak incidence at the significantly lower than in Ashkenazi Jews, suggesting 65-74 years age group and somewhat lower values in the operation of either specific genetic predisposition older patients similar to the data reported from the or some currently undefined acquired factors in these UK6. Comparison to a previously published data on populations. The increased incidence of MPD in the incidence of Polycythemia Vera in Israel, suggests Ashkenazi Jews was clustered in patients from eastern a higher incidence in our patients. In the present study and central Europe with an extremely high incidence a two fold increase was found in Ashkenazi Jews of in those patients originating from Romania, Poland all age groups over 45 years compared to the data by and European USSR. These facts suggest the possibility that some Modan et up. In addition, age specific annual incidence of Polycythemia Vera was 2 folds higher in environmental factors may have been operating in our patients compared with the values reported by the these areas besides genetic predisposition, increased incidence of MPD has been reported as a late sequela large UK study6. The high incidence of Polycythemia Vera found in following radiation exposure" and in Japanese Jews, (20 per 1,000,000)strengthen previous observa- atomic bomb survivors21. In fact while Polycythemia tions in patients of Jewish ancestry reported from the Vera and other M P D are generally rare in Japan, the USA and France4*". We also found a high annual disease is 20 times more common in Nagasaki". incidence of AMM in the population of northern Theoretically, chronic exposure to irradiation in their

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M P D IN NORTHERN ISRAEL

respective countries of origin could potentially play a role and this should be further evaluated by studies comparing the incidence of M P D in the non-Jewish population of eastern Europe to the Jewish population of these countries. Other hemopoietic malignancies are also more common in European Jewish immigrants to Israel compared to matched non-Jewish European populat i o n ~ Since ~ ~ . MPD have been reported following exposure to chemicals24, it is possible that acquired yet undefined environmental factors operating in northern Israel result in the manifestation of MPD in patients with a certain genetic predisposition. Regarding acquired factors it is interesting to note that age at diagnosis was lower in MPD patients with prior biological or chemical exposure and in fact was similar to the age at diagnosis recorded in Arabs and Sephardic Jews. Finally the observation that 4% of our patients had relatives with MPD, a rate which is much higher that expected, but in accordance with a recent reportz5,further emphasizes the importance of genetic factors in the pathogensis of these disorders.

REFERENCES I . Adamson. J. W., Fialkow, P. J., Murphy, S.. Prchal, J. F. and Steinmann, T. (1976) Polycythemia Vera: Stem cell and probable clonal origin of the disease. New England Journal of Medicine. 295, 9 13. 2. Silverstein. M. N. (1986) Agnogenic myeloid metaplasia in: Hematology 3rd edition. Williams, W. J.. Beutler, E.. Erslev, A. J. and Lichtman, M. A. International edition, pp. 214217. 3. Tobelem, G. (1989) Essential thrombocythemia. Baillieres Clin. Hematol., 2, 719. 4. Modan, B. (1965) An epidemiological study of polycythemia Vera. Blood, 26, 657. 5. Silverstein, M. N. and Lanier, A. P. (1971) Polycythemia Vera 1935-1969-an epidemiologic survey in Rochester, Minnesota. Majo. din. Proc., 46, 751. 6. Prochazka, A. V. and Markowe. H. L. J. (1986) The epidemiology of polycythaemia rubra Vera in England and Wales 1968-1 982. British Journal of Cunccv. 53, 59. 7. Dougan, L. E., Mattheus, M. V. L. and Armstrong, B. K. (1981) The effect of diagnostic review on the incidence of lymphatic

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and hematopoietic neoplasms in Western Australia. Cuncri, 48, 866. 8. Mattila, K. (1981) Primaarisen polystemian esintyminen suomessa. Duociecim. 91, 225. 9. Modan, B., Kalliner, M., Lemer, D. and Yoran, C. (1977) A note on the increased risk of polycythemia Vera in Jews. Blood, 37, 172. 10. Najean, Y.. Mognier, P., Oresch, C. and Rain, J. D. (1987) Polycythcmia Vera in young people: An analysis of 58 cases diagnosed before 40 years. British Journul of Haetnntology, 61, 285. 1 I . Woodlim, H. J. and Dougan, L. (1976) Myelofibrosis in western Australia: An epidemiological study of 29 cases. Medical Journal of Austriilia. I. 523-525. 12. Berlin, N. I . (1975) Diagnosis and classification of the polycythemias. Seminurs in Hematolmqj. 12, 3395. 13. Lichtman, M. A. (1990) Agnogenic myeloid metaplasia in Williams, J.. Beutler, E.. Erslev, A. J. and Lichtman, M. A. Hematology 4th Ed McGraw-Hill, N.Y., USA, pp. 223-232. 14. Murphy, S., Iland, H., Rosenthal, D. and Laszlo. J. (1986) Essential thrombocythemia: An interim report from the polycythemia Vera study group. Setninurs in Hematology, 23. 177. 15. Sokal, R. R. and Rohlf. F. J. (1969) Biometry. W H Freeman and Company pp. 175-246. 16. Annual statistical reports 1975-1989-Israel Bureau of Statistics. 17. Kurita. S: Epidemiological studies of polycythemia Vera in Japan. Actu. Hemutolog. Jupan, 37, 793, 1974. 18. Waterhouse, J. A. H. (1974) Cancer handbook of epidemiology and prognosis. Churchill Livingstone, London. 19. Berk, P. D., Goldberg, J. D., Donovan, P. B., Fruchtman, S. M., Berlin, N. I . and Wasserman, L. R. (1986) Therapeutic recommendations in polycythemia Vera based on polycythemia Vera study group protocols. Seminars in Hemutoloqy, 23, 132. 20. Caldwell, G. G., Kelley. D. B., Heath, C. W. and Zack, M. (1984) Polycythemia Vera among participants of a nuclear weapons test. JAMA. 252. 662. 21 Andersen, R. E., Hoshino, T. and Yamamoto, T. (1964) Myelofibrosis with myeloid metaplasia in survivors of the atomic bomb in Hiroshima. Ann. Intern. Mrd., 60, I . 22. Doll, R. and Peto. R. (1981) The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United States today. Oxford University Press, Oxford. 23. Steinitz, R., Parkin, D. M., Young, J. L., Bieber, C. A. and Katz, 1. (1989) Cancer incidence in Jewish migrants to Israel 1961-1981. IARC Scientific Publications no. 98, Lyon. 24. Hu, H. (1987) Benzene-associated myelofibrosis. Ann. Intern. Med., 106. 171-173. 25. Brubaker, L. H., Wasserman, L. R. and Goldberg, J. D. (1984) Increased prevalence of polycythemia Vera in parents of patients. Polycythemia Vera study group protocols. American Journal of Hematology. 16, 361.

High incidence of myeloproliferative disorders in Ashkenazi Jews in northern Israel.

We have analysed epidemiological parameters in 339 patients with myeloproliferative disorders (MPD) diagnosed in northern Israel between 1975 and 1989...
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