Lancet - Evidence Supports Association Between Leukemia And Exposure To Cosmic Radiation In Aircrew Harvey McConnell / DGReview 21dec00

Evidence continues to mount of an association between exposure to cosmic radiation and leukaemia among commercial jet aircrew.

The latest findings in genetic research were obtained in a follow-up on previous research by Dr. Maryanne Gundestrup and colleagues from the National Clinic of Aviation Medicine, University Hospital, and the Institute of Cancer Epidemiology, Copenhagen, Denmark.

In a 1999 report, Dr. Gundestrup and colleagues suggested an association between cosmic radiation exposure at high altitude and an increased risk of myeloid leukaemia among commercial jet aircrew. A second report this year suggests that exposure to cosmic radiation may cause changes to chromosome 7, which is associated with the development of myeloid leukaemia.

In the latest investigation, the researchers studied the karyotypes of seven aircrew treated for myelodysplasia or acute myeloid leukaemia between 1987 and 1999. These findings were compared with the karyotypes of 19 cases of myelodysplasia or acute myeloid leukaemia after radiotherapy between 1980 and 1998.

Researchers then compared the karyotypes of these groups with the range of chromosome aberrations found in 761 patients with myelodysplasia or acute myeloid leukaemia and who had been studied in Lund, Sweden.

Deletion or loss of chromosome 7 was found in four of seven aircrew with myelodysplasia or acute myeloid leukaemia, and in eight of 19 patients with the disorders after radiotherapy alone.

Both the aircrew and radiotherapy groups showed an excess of chromosome abnormality compared with the Swedish data of patients with myelodysplasia or myeloid leukaemia, where only 81 of 761 unselected cases of myelodysplasia or acute myeloid leukemia had the same cytogenetic abnormalities.

Dr. Gundestrup, in a comment on the latest study, said: "Our results indicate that deletions or loss of the long arm of chromosome 7 in myelodysplasia and acute myeloid leukaemia could be an indicator of previous exposure to ionising radiation. Larger studies will be needed to confirm a link between myelodysplasia and acute myeloid leukaemia in aircrew and exposure to cosmic radiation."

Maryanne Gundestrup, Mette Klarskov Andersen, Erla Sveinbjornsdottir, Vilhjálmur Rafnsson, Hans H Storm, Jens Pedersen-Bjergaard

Increased risk of acute myeloid leukaemia has been reported in aircrew, possibly in association with cosmic radiation. We studied the cytogenetics of seven aircrew members who had acute myeloid leukaemia or myelodysplasia and found deletion or loss of chromosome 7 in four. The same abnormality was found in eight of 19 patients with leukaemia after radiotherapy alone. By comparison, only 81 of 761 unselected cases of myelodysplasia or acute myeloid leukaemia had the same cytogenetic abnormalities. Our results support the concept that deletions or loss of the long arm of chromosome 7 in myelodysplasia and acute myeloid leukaemia could indicate previous exposure to ionising radiation.

An increased risk of acute myeloid leukaemia has been reported in aircrew, possibly in association with an increased exposure to cosmic radiation.^1,2Cancer chemotherapy and radiotherapy are known to increase the risk of myelodysplasia and acute myeloid leukaemia. Leukaemia related to treatment with alkylating agents most often presents as myelodysplasia, with deletion or loss of the long arms of chromosomes 5 or 7. Leukaemia related to treatment with topoisomerase-II inhibitors commonly presents as acute myeloid leukaemia with balanced translocations primarily involving chromosome bands 11q23 and 21q22.³ Cytogenetic characteristics of acute myeloid leukaemia after radiotherapy alone have been studied less extensively. We previously saw loss of chromosome 7 in three of eight such cases.⁴ In addition, one out of three patients with acute lymphoblastic leukaemia after radiotherapy alone also had loss of chromosome 7. We postulated that defects of chromosome 7 could serve as a marker for radiation-induced leukaemia.

We studied the karyotypes of seven aircrew treated for myelodysplasia or acute myeloid leukaemia between 1987 and 1999 (table 1), and compared them with the karyotypes, previously published, of 19 cases of myelodysplasia or acute myeloid leukaemia after radiotherapy alone at one of our institutions between 1980 and 1998 (table 2). The karyotypes of these groups were compared with the range of chromosome aberrations found in 761 unselected patients with myelodysplasia or acute myeloid leukaemia, studied in Lund, Sweden.⁵

Age/sex	Year of	Jet flight	FAB-	Karyotype
	diagnosis	hours	type
36/F	1987	5000	M2	45,X,-X,t(8;21)(q22,q22)[8]/46,XX[13]
44/M	1991	2500	M2	45-46,XY,del(3)(p12p13?),add(7)(q36),
				-9,+mar[cp14]/46,XY[11]
58/M	1991	5000	M5	45,XY,-7[9]/46,idem,+mar[5]
73/M	1993	5000	M4	46,XY[31]
57/M	1995	0*	M4	46,XY[12]
68/M	1997	5000	M2	46,XY,del(7)(q31)[22]/47,idem,+22[2]
79/M	1999	5000	RAEB	43,XY,-5,-7,-16,-17,-20,+mar1,+
				mar2[16]/44,idem,+mar3[4]/46,XY[8]
MDS=myelodysplasia; AML=acute myeloid leukaemia.
*Fewer than 1000 propeller flight-hours.
Table 1: Clinical and cytogenetic characteristics of seven cases of myelodysplasia or acute myeloid leukaemia in aircrew

	Aircrew	Radiotherapy-related			Unselected cases
	members	cases
	(n=7)	MDS	AML	Total	MDS	AML	Total
		(n=10)	(n=9)	(n=19)	(n=389)	(n=372)	(n=761)
Normal karyotype	2	3	3	6	190	178	368
Deletion or loss	4	6	2	8	50	31	81
of 7q
Deletion or loss	1	4	0	4	87	46	133
of 5q
Other abnormalities	1	1	4	5	117	136	253
MDS=myelodysplasia; AML=acute myeloid leukaemia.
Table 2: Abnormalities of chromosomes 5 and 7 in cases of myelodysplasia and acute myeloid leukaemia

Deletion or loss of chromosome 7, including a case with an unidentified unbalanced translocation to the long arm, was found in four of seven cases of myelodysplasia or acute myeloid leukaemia in aircrew, and in eight of 19 patients with the disorders after radiotherapy alone. Compared with unselected patients with myelodysplasia or acute myeloid leukaemia, a significant excess of chromosome 7 abnormalities was found in aircrew with leukaemia (p=0·004, Fisher's exact test, two-sided) as well as in the 19 patients with leukaemia related to radiotherapy (p<0·001). There was no difference between the frequency of chromosome 7 abnormalities in the cases of myelodysplasia or acute myeloid leukaemia in aircrew and in the patients treated with radiotherapy alone. It is noteworthy that one patient with only a few flight hours in propeller aircraft had a normal karyotype.

Our results indicate that deletions or loss of the long arm of chromosome 7 in myelodysplasia and acute myeloid leukaemia could be an indicator of previous exposure to ionising radiation. Larger studies will be needed to confirm a link between myelodysplasia and acute myeloid leukaemia in aircrew and exposure to cosmic radiation.

1 Band PR, Le ND, Fang R, et al. Cohort study of Air Canada pilots: mortality, cancer incidence, and leukemia risk. Am J Epidemiol 1996; 143: 137-43. [PubMed]

2 Gundestrup M, Storm HH. Radiation-induced acute myeloid leukaemia and other cancers in commercial jet cockpit crew: a population-based cohort study. Lancet 1999; 354: 2029-31. [Text]

3 Philip P, Pedersen-Bjergaard J. Cytogenetic, clinical, and cytologic characteristics of radiotherapy-related leukaemias. Cancer Genet Cytogenet 1988; 31: 227-236. [PubMed]

4 Pedersen-Bjergaard J, Pedersen M, Roulston D, et al, Different genetic pathways in leukemogenesis for patients presenting with therapy-related myelodysplasia and therapy-related acute myeloid leukaemia. Blood 1995; 86: 3542-52. [PubMed]

5 Mauritzson N, Johansson B, Albin M, et al. A single-center population-based consecutive series of 1500 cytogenetically investigated adult hematological malignancies: karyotypic features in relation to morphology, age and gender. Eur J Haematol 1999; 62: 95-102. [PubMed]

Cytogenetic Laboratory, Section of Haematology/Oncology, The Juliane Marie Center (M Klarskov Andersen MD, J Pedersen-Bjergaard MD), and National Clinic of Aviation Medicine, Cardiological Center (M Gundestrup MD), Rigshospitalet, University Hospital, Copenhagen, Denmark, DK 2200 N; Department of Cancer Prevention, Danish Cancer Society, Copenhagen (M Gundestrup, H H Storm MD); and Departments of Pathology (E Sveinbjornsdottir BSc) and Preventive Medicine (V Rafnsson MD), University of Iceland, Reykjavík, Iceland

Correspondence to: Dr Maryanne Gundestrup, (e-mail:mgflymed@rh.dk)

Evidence Supports Association Between Leukemia

And Exposure To Cosmic Radiation In Aircrew

Cytogenetics of myelodysplasia and acute myeloid leukaemia in aircrew and people treated with radiotherapy