Journal of
J. Neurol. 216, 217--222 (1977)
Neurology @ by Springer-Verlag 1977
Malignant Diseases among Patients with Multiple Sclerosis Jorma Palo 1, Jules Duchesne 2, and Juhani Wikstr6m l i Department of Neurology, University of Helsinki, Haartmaninkatu 4, SF-00290 Helsinki 29, Finland 2Department of Atomic and Molecular Physics, University of Libge, Liege, Belgium
Summary. The frequency of malignant diseases among 1866 living and 340 deceased multiple sclerosis (MS) patients was investigated in Finland. The study revealed a low prevalence (0.64%) and mortality (0.07%) rate of cancer among MS patients. The difference between MS patients and general population was significant. The highest rate was found in the group from 40 to 49 years while in the general population the rate of cancer among MS patients tended to fall after the age of 50. The possible role of selenium, one of the antioxidants in the pathogenesis of MS and cancer, is discussed because recent data have shown a very high negative correlation between selenium and cancer death rates. Key words: Epidemiology - Multiple sclerosis - Cancer - Antioxidant (selenium).
Zusammenfassung. Die Malignomenfrequenz bei 1866 lebenden und 340 verstorbenen Multiple-Sklerose (MS)-Patienten wurde in Finnland untersucht. Dabei wurde eine niedrige Pr~ivalenz- (0.64%) und Mortalit~itsrate (0.07%) for Karzinom ermittelt. Der Unterschied zwischen den MS-Patienten und der Normalbev61kerung war signifikant. Die h6chste Inzidenzrate war in der Altersgruppe von 40 bis 49 Jahren festzustellen. Anders wie bei der Normalbev61kerung nahm bei den MS-Patienten die Karzinomfrequenz nach dem ftinfzigsten Lebensjahr st~indig ab. Die m6gliche Rolle Seleniums, eines Antioxydants, in der Pathogenese yon MS und Karzinom wurde diskutiert, denn neue Ergebnisse haben eine hohe negative Korrelation zwischen Selenium und Karzinommortalit~it erwiesen.
Several theories have been presented concerning the etiology and pathogenesis of multiple sclerosis (MS). In addition to the viral hypothesis (see e.g. ter Meulen et al., 1972) a theory which involves the imbalance of polyunsaturated fatty acids has received wide attention (Swank et al., 1952). The role of antioxidants, which have been shown to protect the organism against peroxidation, has been
218
J. Palo et al.
discussed in this c o n t e x t (Duchesne, 1975, 1977). P a r t i c u l a r a t t e n t i o n has been p a i d to selenium, one o f the a n t i o x i d a n t s . While it is possible that high c o n c e n t r a t i o n s o f selenium in the o r g a n i s m might enhance carcinogenesis, recent d a t a have shown a very high negative c o r r e l a t i o n between the selenium level o f the b l o o d o f a d u l t males in the U n i t e d States a n d h u m a n cancer d e a t h rates ( S h a m b e r g e r a n d F r o s t , 1969). T h e e p i d e m i o l o g y o f MS has been studied extensively in F i n l a n d for years. It b e c a m e a p p a r e n t d u r i n g these studies t h a t the g e o g r a p h i c d i s t r i b u t i o n o f MS p a r a l l e l e d t h a t o f n u t r i t i o n a l m u s c u l a r d y s t r o p h y ( N M D ) o f cattle (Palo et al., 1973). N M D is etiologically related to a low level o f selenium a n d can be cured with this agent. Because the highest incidence o f these two diseases was f o u n d in the s a m e district o f F i n l a n d it was a s s u m e d that MS patients m a y also have low levels o f selenium. In fact, the selenium content o f whole b l o o d was low in M S patients f r o m this high risk a r e a c o m p a r e d to the c o n t r o l s a l t h o u g h all selenium values were lower t h a n the i n t e r n a t i o n a l values suggested ( W i k s t r 6 m et al., 1976). This finding led us to investigate the frequency o f c o m b i n a t i o n s o f MS and m a l i g n a n t processes. It was b a s e d on the a s s u m p t i o n t h a t they w o u l d be rare if carcinogenesis is etiologically related to increased c o n c e n t r a t i o n s o f selenium.
Materials and Methods A series of 1.866 living MS patients was collected from the central hospitals and clinics of neurology, psychiatry and medicine, and from the National Pension Institute of Finland (Wikstr/3m and Palo, 1975). The criteria of the Schumacher Committee (Schumacher et al., 1965) were applied. Data for a series of 340 deceased MS patients were collected from the Central Statistical Office of Finland (Wikstr6m, 1975). The prevalence day for the living patients was December, 1971. The mortality data were from 1963 to 1971. The data for malignant diseases were collected from the Finnish Cancer Registry where all cancer patients are reported. Such reporting has been obligatory since 1961. All hospitals, laboratories of pathology and cytology, as well as private practitioners are requested to report all new cases of cancer that come to their attention (Teppo et al., 1975). The Registry also receives copies of all death certificates where cancer is mentioned. Furthermore, it makes annual checks against all death certificates issued in Finland. Accordingly, information is obtained not only from cancer deaths but from deaths due to other causes.
Results Twelve certain cases o f m a l i g n a n t diseases were r e p o r t e d a m o n g the 1866 living M S p a t i e n t s b y the e n d o f 1971 (Table 1). T h e r e were 9 females a n d 3 males with a m e a n age o f 49.9 years. In all cases the diagnosis was b a s e d u p o n histological c o n f i r m a t i o n o f the t u m o r . Six a d d i t i o n a l cases were excluded because they were d i a g n o s e d after the prevalence day. Five patients with b a s a l i o m a (basal cell c a r c i n o m a ) , 2 cases o f c a r c i n o m a in situ o f the cervix uteri, a n d 1 case o f p a p i l l o m a o f the u r i n a r y b l a d d e r were also excluded because they were n o t c o n s i d e r e d m a l i g n a n t . T h e prevalence o f cancer was thus 0.64% (Table 4). The a g e - a d j u s t e d rat~ o f cancer p e r 100 000 males o f the general F i n n i s h p o p u l a t i o n was 664.6 o n D e c e m b e r 31, 1970, a n d 784.2 p e r 100000 females ( T e p p o et al.,
Malignant Diseases among Fatients with Multiple Sclerosis
219
Table 1. The cases of malignant diseases among 1,866 living MS patients (prevalence day December 31, 1971) reported to the Finnish Cancer Registry. (The age is given in years at the time of the malignant disease) Patient
Sex
Age
Diagnosis (localization)
PAD
F.M. H.M. H.E. J.K. K.A. K.H. K.J. K.E. K.V. L.I. P.P. S.A.
F M F F F F F F M F M F
45 42 45 49 60 45 50 40 42 59 29 35
Ca mammae Melanoma malignum (skin) Sarcoma-fibrosarcoma (thigh) Ca ductale mammae Ca mammae Ca ductale mammae Ca anaplasticum corporis uteri Melanoma malignum (skin) Ca epidermoides (larynx) Ca ductale mammae cum metast. Lymphoma malignum Ca adenomatosum (uterus)
+ + + + + + + + + + + +
Table 2. The age-specific indicidence rate of malignant diseases among MS patients in comparison to corresponding figures for general population Age-group
20--29 30--39 40--49 50--59 60--69 70
Incidence of malignant diseases per 100,000among MS patientsa
general populationb
40.4 (1) 35.6 (2) 109.6 (lO) 69.0 (4) 100.6 (3) 198.4 (1)
22.3 64.6 186.7 449.9 949.7 1,763.5
Data taken from Wikstr6m and Palo (1975). The number of cases is given in parentheses (n = 21) b Data taken from Teppo et al. (1975) a
1975) giving a prevalence of 0.72% for the whole general p o p u l a t i o n . The difference between MS patients a n d the general p o p u l a t i o n was significant
( e < 0.05). The age-specific c u m u l a t i v e incidence rates o f cancer a m o n g MS patients are presented in T a b l e 2. These figures are based u p o n 21 MS patients who were reported b e t w e e n the years 1961 a n d 1974, b o t h years included. The highest incidence rate was f o u n d in the g r o u p f r o m 40 to 49 years. A l t h o u g h the groups were small the incidence rate o f cancer a m o n g MS patients h a d a declining t e n d e n c y at a higher age while a distinct rise of the incidence rate was observed in the general p o p u l a t i o n after the age of 50. O n l y 3 cases of cancer were f o u n d a m o n g the 340 patients who died b e t w e e n 1963 a n d 1971 a n d were r e p o r t e d to the C e n t r a l Statistical Office where u n d e r l y i n g a n d direct causes o f death are registered. However, a search o f the
220
J. Palo et al.
Table 3. A. The cases of malignant diseases among 340 MS patients who died between 1963 and 1971. B. The cases of malignant diseases with additional of MS as reported to the Finnish Cancer Registry between 1963 und 1971 Patient
Sex
Age at death
Diagnosis
L.J. W.A. K.J.
M F F
68 58 48
Ca pulmonis Ca epidermoides (collum uteri) Ca anaplasticum mammae
B) B.L. H.T. 1. H. K.S. O.E. P.A. S.E.
F M F F M F M
54 42 52 63 68 63 52
S.E. S.A.
M M
61 70
Ca mammae cum metast. Ca pulmonum cum metast. Astrocytoma (brain) Ca auris Neoplasma malignum (stomach) Neoplasma coeci Ca adenomatosum cure metast. (stomach) Ca pulmonum Ca epidermoides (lung)
PAD
A) + + + +
+ + +
Table 4. Malignant diseases among living and deceased MS patients in comparison to corresponding figures for general population Prevalence Living MS patients (n = 1.866)~ 0.64% General populationb 0.72%
Mortality Deceased MS patients (n = 340)c 0.07% General populationb 0.15% Prevalence date 31, 1971 (Data taken from Wikstr6m and Palo, 1975) b Data taken from Teppo et al. (1975) Data taken from Wikstr6m (1975)
C a n c e r Registry revealed 9 a d d i t i o n a l cases b r i n g i n g the total to 12 cases (Table 3). O n e case of b a s a l i o m a , 1 n e u r o f i b r o m a , a n d one o v a r i a n t u m o r w i t h o u t p a t h o l o g i c a l diagnosis were excluded. A total of 0.07% of the MS patients thus died f r o m cancer (Table 4). The age-adjusted mortality rate for cancer is 191.8 per 100,000 males a n d 103.7 per 100000 females of the general p o p u l a t i o n (Teppo et al., 1975). The c o r r e s p o n d i n g figure for the whole general p o p u l a t i o n is 0.15%. The difference between MS patients a n d the n o r m a l p o p u l a t i o n was significant (P < 0.05).
Malignant Diseases among Patients with Multiple Sclerosis
221
Discussion The theory of the pathogenetic role of insufficient amounts of polyunsaturated fatty acids in the diet for the development of MS has been presented earlier (Clausen et al., 1972).The idea that peroxide polyunsaturated fatty acids have a role in the development of that disease (Duchesne, 1975; Millar et al., 1973) is an extension of that theory and similar to that presented for myocardial infarction (Anderson, 1973). The fact that N M D can be cured with selenium confirms that, at least for N M D , the amount of this element is insufficient to protect the organism against peroxidation. Although selenium and other elements which play a role in the protection have also been used for Batten's disease (neuronal ceroid-lipofuscinosis or Spielmeyer-Sjrgren's disease) both in Finland and in the U.S., we are not aware of corresponding therapy for MS. Slight improvement was observed in MS patients with linoleate supplementation of the diet but the overall course of the disease was not changed (Millar et al., 1973). The theory of low levels of trace elements in the organism as a factor in the pathogenesis of MS excludes, at least partly, the presence of cancer in MS patients (Duchesne, 1975). The prevalence of cancer a m o n g animals with N M D cannot be studied because the cattle are slaughtered before the age when neoplasms would become manifest. The present study demonstrated a relative incompatibility between MS and cancer although the total number of cancer patients was rather small and the findings should be confirmed by further study. However, they agree with the previous results of Maretschek et al. (1954) who showed a very significant difference in autopsy material. The authors also discussed the possible cytostatic factor in MS patients. In the present study the declining incidence rate of cancer a m o n g MS patients after the age of 50 may point to such a factor although it may also be explained by the somewhat lower age of the MS patients at death. Uneven geographic distribution is a characteristic feature of MS. A m o n g a number of h u m a n diseases only cancer of the colon appears to have similar distribution (Wolfgram, 1975). The possible role of dietary factors in the pathogenesis of the two conditions is unknown at the moment. In summary, the present study revealed a low prevalence and mortality rate of cancer a m o n g MS patients. This supports the idea of peroxide polyunsaterated fatty acids having a role in the pathogenesis of MS. However, the total number of cancer cases was small among MS patients and therefore large, cumulative figures are required. We thank the personnel of the Finnish Cancer Registry and the Central Statistical Office for cooperation, and Miss K. Lindberg for technical assistance. The National Research Council for Medical Sciences of Finland gave financial support.
References Anderson, T. W.: Nutritional muscular dystrophy and human myocardial infarction. Lancet 1973 II, 298--302 Clausen, J., Fog, T., Hansen, I. B.: Myelin constituents in multiple sclerosis. In: Progress in Multiple Sclerosis (ed. U. Leibowitz), pp. 60--75. New York-London: Academic Press 1972
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J.Palo et al.
Duchesne, J.: Radicaux libres organiques, antioxydants, srnescence, longrvit6 maximale et cancer. Bull. Acad. Royale Belg. 61,633--639 (1975) Duchesne, J.: A unifying biochemical theory of cancer, senescence and maximal life span. J. theor. Biol. 66, 137--145 (1977) Maretschek, M., Schaltenbrand, G., Seibert, P.: Statistische Untersuchungen fiber die Multiple Sklerose an Hand von 947 Sektionsprotokollen. Dtsch. Z. Nervenheilk. 172,287--308 (1954) Millar, J. H. D., Zilkha, K. J., Langman, M. J. S., Payling Wright, H., Smith, A. D., Belin, J., Thompson, R. H. S.: A double-blindtrial of linoteate supplementation of the diet in multiple sclerosis. Brit. Med. J. 1973 I, 765--768 Palo, J., Wikstrrm, J., Kivalo, E.: Epidemiology of nutritional muscular dystrophy and multiple sclerosis. Lancet 1973 II, 848 Schumacher, G. A., Beebe, G., Kibler, R. F., Kurland, L. T., Kurtzke, J. F., McDowell, F., Nagler, B., Sibley, W. A., Tourtelotte, W. W., Willmon, T. L.: Problems of experimental trials of therapy in multiple sclerosis: report by the panel of the evaluation of experimental trials of therapy in multiple sclerosis. Ann. N. Y. Acad. Sci. 122, 552--568 (1965) Shamberger, R. J., Frost, D. V.: Possible protective effect of selenium against human cancer. Can. Med. Assn. J. 100, 682 (1969) Swank, R. L., Lerstad, O., Strrm, A., Backer, J.: Multiple sclerosis in rurral Norway. Its geographic and occupational incidence in relation to nutrition. New Engl. J. Med. 246,721-728 (1952) Teppo, L., Hakama, M., Hakulinen, T., Lehtonen, M., Saxrn, E.: Cancer in Finland 1953--1970: incidence, mortality, prevalence. Acta path. microbiol, scand. Sect. A Suppl. 252, 1--79 (1975) Wikstrrm, J.: The epidemiology of multiple sclerosis and tuberculosis in Finland. Acta neurol. scand. 52, 207--215 (1975) Wikstrrm, J., Palo, J.: Studies on the clustering of multiple sclerosis in Finland I: comparison between the domiciles and places of birth in selected subpopulations. Acta neurol, scand. 51, 85--98 (1975) Wikstrrm, J., Westermarck, T., Palo, J.: Selenium, vitamin E and copper in multiple sclerosis. Acta neurol, scand. 54, 287--290 (1976) Wolfgram, F.: Similar geographical distribution of multiple sclerosis and cancer of the colon. Acta neurol, scand. 52, 294--302 (1975)
Received May 12, 1976
J. Neurol. 216, 217--222 (1977)
Neurology @ by Springer-Verlag 1977
Malignant Diseases among Patients with Multiple Sclerosis Jorma Palo 1, Jules Duchesne 2, and Juhani Wikstr6m l i Department of Neurology, University of Helsinki, Haartmaninkatu 4, SF-00290 Helsinki 29, Finland 2Department of Atomic and Molecular Physics, University of Libge, Liege, Belgium
Summary. The frequency of malignant diseases among 1866 living and 340 deceased multiple sclerosis (MS) patients was investigated in Finland. The study revealed a low prevalence (0.64%) and mortality (0.07%) rate of cancer among MS patients. The difference between MS patients and general population was significant. The highest rate was found in the group from 40 to 49 years while in the general population the rate of cancer among MS patients tended to fall after the age of 50. The possible role of selenium, one of the antioxidants in the pathogenesis of MS and cancer, is discussed because recent data have shown a very high negative correlation between selenium and cancer death rates. Key words: Epidemiology - Multiple sclerosis - Cancer - Antioxidant (selenium).
Zusammenfassung. Die Malignomenfrequenz bei 1866 lebenden und 340 verstorbenen Multiple-Sklerose (MS)-Patienten wurde in Finnland untersucht. Dabei wurde eine niedrige Pr~ivalenz- (0.64%) und Mortalit~itsrate (0.07%) for Karzinom ermittelt. Der Unterschied zwischen den MS-Patienten und der Normalbev61kerung war signifikant. Die h6chste Inzidenzrate war in der Altersgruppe von 40 bis 49 Jahren festzustellen. Anders wie bei der Normalbev61kerung nahm bei den MS-Patienten die Karzinomfrequenz nach dem ftinfzigsten Lebensjahr st~indig ab. Die m6gliche Rolle Seleniums, eines Antioxydants, in der Pathogenese yon MS und Karzinom wurde diskutiert, denn neue Ergebnisse haben eine hohe negative Korrelation zwischen Selenium und Karzinommortalit~it erwiesen.
Several theories have been presented concerning the etiology and pathogenesis of multiple sclerosis (MS). In addition to the viral hypothesis (see e.g. ter Meulen et al., 1972) a theory which involves the imbalance of polyunsaturated fatty acids has received wide attention (Swank et al., 1952). The role of antioxidants, which have been shown to protect the organism against peroxidation, has been
218
J. Palo et al.
discussed in this c o n t e x t (Duchesne, 1975, 1977). P a r t i c u l a r a t t e n t i o n has been p a i d to selenium, one o f the a n t i o x i d a n t s . While it is possible that high c o n c e n t r a t i o n s o f selenium in the o r g a n i s m might enhance carcinogenesis, recent d a t a have shown a very high negative c o r r e l a t i o n between the selenium level o f the b l o o d o f a d u l t males in the U n i t e d States a n d h u m a n cancer d e a t h rates ( S h a m b e r g e r a n d F r o s t , 1969). T h e e p i d e m i o l o g y o f MS has been studied extensively in F i n l a n d for years. It b e c a m e a p p a r e n t d u r i n g these studies t h a t the g e o g r a p h i c d i s t r i b u t i o n o f MS p a r a l l e l e d t h a t o f n u t r i t i o n a l m u s c u l a r d y s t r o p h y ( N M D ) o f cattle (Palo et al., 1973). N M D is etiologically related to a low level o f selenium a n d can be cured with this agent. Because the highest incidence o f these two diseases was f o u n d in the s a m e district o f F i n l a n d it was a s s u m e d that MS patients m a y also have low levels o f selenium. In fact, the selenium content o f whole b l o o d was low in M S patients f r o m this high risk a r e a c o m p a r e d to the c o n t r o l s a l t h o u g h all selenium values were lower t h a n the i n t e r n a t i o n a l values suggested ( W i k s t r 6 m et al., 1976). This finding led us to investigate the frequency o f c o m b i n a t i o n s o f MS and m a l i g n a n t processes. It was b a s e d on the a s s u m p t i o n t h a t they w o u l d be rare if carcinogenesis is etiologically related to increased c o n c e n t r a t i o n s o f selenium.
Materials and Methods A series of 1.866 living MS patients was collected from the central hospitals and clinics of neurology, psychiatry and medicine, and from the National Pension Institute of Finland (Wikstr/3m and Palo, 1975). The criteria of the Schumacher Committee (Schumacher et al., 1965) were applied. Data for a series of 340 deceased MS patients were collected from the Central Statistical Office of Finland (Wikstr6m, 1975). The prevalence day for the living patients was December, 1971. The mortality data were from 1963 to 1971. The data for malignant diseases were collected from the Finnish Cancer Registry where all cancer patients are reported. Such reporting has been obligatory since 1961. All hospitals, laboratories of pathology and cytology, as well as private practitioners are requested to report all new cases of cancer that come to their attention (Teppo et al., 1975). The Registry also receives copies of all death certificates where cancer is mentioned. Furthermore, it makes annual checks against all death certificates issued in Finland. Accordingly, information is obtained not only from cancer deaths but from deaths due to other causes.
Results Twelve certain cases o f m a l i g n a n t diseases were r e p o r t e d a m o n g the 1866 living M S p a t i e n t s b y the e n d o f 1971 (Table 1). T h e r e were 9 females a n d 3 males with a m e a n age o f 49.9 years. In all cases the diagnosis was b a s e d u p o n histological c o n f i r m a t i o n o f the t u m o r . Six a d d i t i o n a l cases were excluded because they were d i a g n o s e d after the prevalence day. Five patients with b a s a l i o m a (basal cell c a r c i n o m a ) , 2 cases o f c a r c i n o m a in situ o f the cervix uteri, a n d 1 case o f p a p i l l o m a o f the u r i n a r y b l a d d e r were also excluded because they were n o t c o n s i d e r e d m a l i g n a n t . T h e prevalence o f cancer was thus 0.64% (Table 4). The a g e - a d j u s t e d rat~ o f cancer p e r 100 000 males o f the general F i n n i s h p o p u l a t i o n was 664.6 o n D e c e m b e r 31, 1970, a n d 784.2 p e r 100000 females ( T e p p o et al.,
Malignant Diseases among Fatients with Multiple Sclerosis
219
Table 1. The cases of malignant diseases among 1,866 living MS patients (prevalence day December 31, 1971) reported to the Finnish Cancer Registry. (The age is given in years at the time of the malignant disease) Patient
Sex
Age
Diagnosis (localization)
PAD
F.M. H.M. H.E. J.K. K.A. K.H. K.J. K.E. K.V. L.I. P.P. S.A.
F M F F F F F F M F M F
45 42 45 49 60 45 50 40 42 59 29 35
Ca mammae Melanoma malignum (skin) Sarcoma-fibrosarcoma (thigh) Ca ductale mammae Ca mammae Ca ductale mammae Ca anaplasticum corporis uteri Melanoma malignum (skin) Ca epidermoides (larynx) Ca ductale mammae cum metast. Lymphoma malignum Ca adenomatosum (uterus)
+ + + + + + + + + + + +
Table 2. The age-specific indicidence rate of malignant diseases among MS patients in comparison to corresponding figures for general population Age-group
20--29 30--39 40--49 50--59 60--69 70
Incidence of malignant diseases per 100,000among MS patientsa
general populationb
40.4 (1) 35.6 (2) 109.6 (lO) 69.0 (4) 100.6 (3) 198.4 (1)
22.3 64.6 186.7 449.9 949.7 1,763.5
Data taken from Wikstr6m and Palo (1975). The number of cases is given in parentheses (n = 21) b Data taken from Teppo et al. (1975) a
1975) giving a prevalence of 0.72% for the whole general p o p u l a t i o n . The difference between MS patients a n d the general p o p u l a t i o n was significant
( e < 0.05). The age-specific c u m u l a t i v e incidence rates o f cancer a m o n g MS patients are presented in T a b l e 2. These figures are based u p o n 21 MS patients who were reported b e t w e e n the years 1961 a n d 1974, b o t h years included. The highest incidence rate was f o u n d in the g r o u p f r o m 40 to 49 years. A l t h o u g h the groups were small the incidence rate o f cancer a m o n g MS patients h a d a declining t e n d e n c y at a higher age while a distinct rise of the incidence rate was observed in the general p o p u l a t i o n after the age of 50. O n l y 3 cases of cancer were f o u n d a m o n g the 340 patients who died b e t w e e n 1963 a n d 1971 a n d were r e p o r t e d to the C e n t r a l Statistical Office where u n d e r l y i n g a n d direct causes o f death are registered. However, a search o f the
220
J. Palo et al.
Table 3. A. The cases of malignant diseases among 340 MS patients who died between 1963 and 1971. B. The cases of malignant diseases with additional of MS as reported to the Finnish Cancer Registry between 1963 und 1971 Patient
Sex
Age at death
Diagnosis
L.J. W.A. K.J.
M F F
68 58 48
Ca pulmonis Ca epidermoides (collum uteri) Ca anaplasticum mammae
B) B.L. H.T. 1. H. K.S. O.E. P.A. S.E.
F M F F M F M
54 42 52 63 68 63 52
S.E. S.A.
M M
61 70
Ca mammae cum metast. Ca pulmonum cum metast. Astrocytoma (brain) Ca auris Neoplasma malignum (stomach) Neoplasma coeci Ca adenomatosum cure metast. (stomach) Ca pulmonum Ca epidermoides (lung)
PAD
A) + + + +
+ + +
Table 4. Malignant diseases among living and deceased MS patients in comparison to corresponding figures for general population Prevalence Living MS patients (n = 1.866)~ 0.64% General populationb 0.72%
Mortality Deceased MS patients (n = 340)c 0.07% General populationb 0.15% Prevalence date 31, 1971 (Data taken from Wikstr6m and Palo, 1975) b Data taken from Teppo et al. (1975) Data taken from Wikstr6m (1975)
C a n c e r Registry revealed 9 a d d i t i o n a l cases b r i n g i n g the total to 12 cases (Table 3). O n e case of b a s a l i o m a , 1 n e u r o f i b r o m a , a n d one o v a r i a n t u m o r w i t h o u t p a t h o l o g i c a l diagnosis were excluded. A total of 0.07% of the MS patients thus died f r o m cancer (Table 4). The age-adjusted mortality rate for cancer is 191.8 per 100,000 males a n d 103.7 per 100000 females of the general p o p u l a t i o n (Teppo et al., 1975). The c o r r e s p o n d i n g figure for the whole general p o p u l a t i o n is 0.15%. The difference between MS patients a n d the n o r m a l p o p u l a t i o n was significant (P < 0.05).
Malignant Diseases among Patients with Multiple Sclerosis
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Discussion The theory of the pathogenetic role of insufficient amounts of polyunsaturated fatty acids in the diet for the development of MS has been presented earlier (Clausen et al., 1972).The idea that peroxide polyunsaturated fatty acids have a role in the development of that disease (Duchesne, 1975; Millar et al., 1973) is an extension of that theory and similar to that presented for myocardial infarction (Anderson, 1973). The fact that N M D can be cured with selenium confirms that, at least for N M D , the amount of this element is insufficient to protect the organism against peroxidation. Although selenium and other elements which play a role in the protection have also been used for Batten's disease (neuronal ceroid-lipofuscinosis or Spielmeyer-Sjrgren's disease) both in Finland and in the U.S., we are not aware of corresponding therapy for MS. Slight improvement was observed in MS patients with linoleate supplementation of the diet but the overall course of the disease was not changed (Millar et al., 1973). The theory of low levels of trace elements in the organism as a factor in the pathogenesis of MS excludes, at least partly, the presence of cancer in MS patients (Duchesne, 1975). The prevalence of cancer a m o n g animals with N M D cannot be studied because the cattle are slaughtered before the age when neoplasms would become manifest. The present study demonstrated a relative incompatibility between MS and cancer although the total number of cancer patients was rather small and the findings should be confirmed by further study. However, they agree with the previous results of Maretschek et al. (1954) who showed a very significant difference in autopsy material. The authors also discussed the possible cytostatic factor in MS patients. In the present study the declining incidence rate of cancer a m o n g MS patients after the age of 50 may point to such a factor although it may also be explained by the somewhat lower age of the MS patients at death. Uneven geographic distribution is a characteristic feature of MS. A m o n g a number of h u m a n diseases only cancer of the colon appears to have similar distribution (Wolfgram, 1975). The possible role of dietary factors in the pathogenesis of the two conditions is unknown at the moment. In summary, the present study revealed a low prevalence and mortality rate of cancer a m o n g MS patients. This supports the idea of peroxide polyunsaterated fatty acids having a role in the pathogenesis of MS. However, the total number of cancer cases was small among MS patients and therefore large, cumulative figures are required. We thank the personnel of the Finnish Cancer Registry and the Central Statistical Office for cooperation, and Miss K. Lindberg for technical assistance. The National Research Council for Medical Sciences of Finland gave financial support.
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Received May 12, 1976
