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INCREASED INCIDENCE OF MALIGNANT MELANOMA AFTER PEAKS OF SUNSPOT ACTIVITY
759
Occasional
Survey
INCREASED INCIDENCE OF MALIGNANT MELANOMA AFTER PEAKS OF SUNSPOT ACTIVITY ALAN HOUGHTON EDWARD W. MUNSTER MICHAEL V. VIOLA
Oncology Division, Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut 06032, U.S.A.
Summary
age-adjusted incidence-rate for malignant melanoma in the State of The
Connecticut has risen from 1·1 per 100 000 individuals in 1935 to 6·2 per 100 000 individuals in 1975. Superimposed on a steady rise in incidence are 3-5 year periods in which the rate of increase in incidence rises. These periods have a cycle of 8-11 years and follow times of maximum sunspot activity.
Year incidence of malignant melanoma in the State of Connecticut per 100 000 persons.
Age-adjusted -
=males and females; -=males alone. Arrows indicate the
peak of sunspot activity. INTRODUCTION
THE aetiology of melanoma is complex and may include the influences of trauma, heredity, and hormonal activity. Several observations suggest that solar radiation may also have a role; melanoma is more common in fair-skinned individuals2 and is most frequent at skinsites exposed to the sun,3and in white populations is more common in areas closer to the equator4,5 where the intensity of solar radiation is higher. Data from various parts of the world suggest that the incidence of melanoma is increasing6,7 and several reviewers5,7,8 support this view. We have reviewed data from the Connecticut Tumor Registry-which has the longest record of State population-based cancer statistics in the United States-in an attempt to define more precisely the increasing incidence-rates in this state. METHODS
2983 cases of histologically proven melanoma registered in the Connecticut Tumor Registry in 1935-74 were reviewed. Methods of data collection and statistical analysis were published previously.9 The statistical package for social scienceslO was used on a ’Univac 1106’ computer for calculating correlations and regressions. Incidence curves were smoothed by the 3RSSH,2 method of Tukey. II Relative sunspot numbers were obtained from Waldmeirl2 and Eddy."
This cyclic pattern of melanoma incidence led us to attempt correlations with other cyclic events, the most obvious being the sunspot cycle (see figure). Each period in which the incidence of melanoma rose sharply began at the peak of a sunspot cycle and persisted for 3-5 years before falling. The most recent rise in incidence, which began in the mid-1960s, was the greatest but in 1975 had yet to form a plateau. The secular increase in the incidence of melanoma can be represented by a linear regression equation relating melanoma (non-smoothed, age-adjusted incidencerates) to time over three sunspot cycles (33 years). This correlation coequation has a significant (P<0-01) efficient (0-9327). The independent effect of sunspot cycles was examined by calculating the deviation from the regression equation-i.e., removing the effect of increasing rates with time. The deviations from the linear regression line were cyclic. We calculated the partial correlations of annual sunspot numbers with melanoma incidence, controlling for the linear time effect and found statistically significant partial correlations between the sunspot number and the melanoma incidence-rates in each of the subsequent three years, the closest association being that with the incidence two years later (table I). Data from cancer registries in New York State,14 Nor-
RESULTS TABLE I-PARTIAL CORRELATION COEFFICIENTS RELATING
The age-adjusted incidence-rate of melanoma in Connecticut rose from 1-11 per 100 000 individuals in 19355 to 6.2 per 100 000 individuals in 1975 (see figure). The incidence-rate doubled between 1950 and 1975. Superimposed on a steady rise in incidence over forty years were periods during which the rise in incidence became more acute, reaching a peak in 3-5 years, before returning to the baseline rates of increase. Between 1935 and 1975 this cycle occurred four times, with 8-11 year
intervals.
ANNUAL SUNSPOT NUMBER TO MELANOMA INCIDENCE
p
values are shown in parentheses.
N.s.=not
significant.
(1935-67)
760 TABLE II-PARTIAL CORRELATION COEFFICIENTS RELATING ANNUAL SUNSPOT NUMBER TO MELANOMA INCIDENCE
p-values are shown in parentheses.
rt.s.=not
1950-71
significant.
and Finland16 for 1950-71 were analysed in a similar way. In New York State, like Connecticut, there were significant partial correlations between the annual sunspot number and the melanoma incidence-rates in the subsequent 1-2 years (table II). A different pattern was observed in Finland where the increased incidencerates were significantly correlated with the years of sunspot activity and with the first subsequent year.
way,"
DISCUSSION
Two independent variables affect the incidence of melanoma in Connecticut-a linear increase with time, which has been observed by other investigators,7 and cyclic increases which lag approximately two years after sunspot activity. We were unable to correlate the cyclic increases in the incidence of melanoma with any major economic oscillations, variations in dressing behaviour, or mores. It is unlikely that the cycles are related to census timing (every ten years) since the population at risk is estimated retrospectively for non-census years by trend lines9 and the cyclic increases in the incidence of melanoma occur randomly in relation to census years. There is no cyclic pattern in data from the Connecticut Tumor Registry on the incidence of cancer of the stomach,17 cervix,t8 endometrium,19 breast, 20 colorectum,21 lung,21 or in the incidence of Hodgkin’s disease.22 A cyclic pattern of similar type was detected in data from New York State and Connecticut although no such relationship was established in data from Norway. The lag period between sunspot cycles and the cyclic increases in the incidence of melanoma was longer in Connecticut than in Finland. This effect may be latitudinal and could be important in constructing a mechanism of
sunspot-induced carcinogenesis. The sunspot phenomenon has a complex relationship to other geophysical and astrophysical events.23,24 Modification of the solar wind magnetic fields associated with sunspot cycles can influence galactic cosmic rays entering the stratosphere. The increased collisions between cosmic rays and stratospheric particles generate free nitrogen atoms and negative ions, both of which can catalyse the destruction of stratospheric ozone.25 Stratospheric ozone absorbs potentially carcinogenic ultraviolet radiation (U.V.-B.) (290-320 nm), limiting the amount reaching the earth’s surface. The reduction of stratospheric ozone associated with sunspot cycles ismost prominent at the polar caps but, with time, can diffuse to lower latitudes. Thus, the lag period between sunspot cycles and the cyclic increases in the incidence
of melanoma in areas at higher latitudes might be expected to be shorter than in
(e.g., Finland) areas at
lower
latitudes (e.g., Connecticut). Evidence for the role of u.v.-B. in the aetiology of’ melanoma has been summarised in the report of the Climatic Impact Committee of the National Academy of Sciences26 which contains several models (interpolation formulas) relating stratospheric ozone reduction and U.V.-B. flux at the earth’s surface to the incidence of melanoma. The rate of increase in melanoma in Connecticut following sunspot cycles (e.g., 1946-1949, 1957-1960) exceeds that predicted by these models. The ozone reduction associated with sunspot cycles is 1-3%. However the incidence of melanoma may be influenced by other variables which affect u.v.-B. flux at the earth’s surface,26 as well as by other carcinogens, outdoor recreational habits, and the susceptibility of individuals within the population. Requests for reprints should be addressed to M. V. V., Oncology Division, Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut 06032, U.S.A. REFERENCES 1. 2. 3. 4.
Lee, J. A. H. in Progress in Clinical Cancer; p. 151 New York, 1975. Lancaster, H., Nelson, J. Med. J. Aust. 1957, i, 452. Davis, N. C., Herron, J. J., McLeod, G. R. Lancet, 1966, ii, 407. Elwood, J. M., Lee, J. A. H., Walter, S. D., Mo, T., Green, A. Int. J. Epi-
demiol. 1974, 3, 325. 5. Magnus, K. Cancer, 1973, 32, 1275. 6. Burbank, F. in Patterns of Cancer Mortality in the United States 1950-1967. N n. Cancer Inst. Monograph; p. 33, 1971. 7. Lee, J. A. H., Carter, A. P. J. Cancer Inst. 1970, 45, 91. 8. Viola, M. V., Houghton, A. Conn. Med. (in the press). 9. Eisenberg, N., Campbell, P:, Flannery, J. Cancer in Connecticut 1935-1962. Connecticut State Department of Health. Hartford, 1967. 10. Nie, W., Hull, C., Jenkins, J., Steinbrenner, K., Bent, D. Statistical Package for Social Sciences. New York, 1975. 11. Tukey, J. Exploratory Data Analysis; p. 523. Reading, Massachusetts, 1977. 12. Waldmeir, M. W. Sunspot Activity in Zurich, 1610-1960. Zurich, 1961. 13. Eddy, J. Science, 1976, 192, 1189. 14. Greenwald, P., and others. Cancer Incidence and Mortality in New York State. Bureau of Cancer Control, New York State Department of Health, 1976. 15. The Cancer Registry of Norway. Trends in Cancer Incidence in Norway, 1955-1967. Oslo, 1972. 16. Finnish Cancer Registry: Cancer Incidence in Finland. Cancer Society of Finland. Helsinki, 1965-1976. 17. Nonoz, N., Connelly, R. Int. J. Cancer, 1970, 8, 164. 18. Christine, B., Chapple, M., Nadeau, D. Conn. Med. 1972, 36, 669. 19. Cramer, D., Cutler, S. J., Christine, B. Gynec. Oncol. 1970, 2, 130. 20. Cutler, S. J., Connelly, R. Cancer, 1964, 23, 767. 21. Houghton, A., Munster, E. W., Viola, M. V. Unpublished. 22. Krypico, F., Myers, M., Prusiner, S., Heise, H., Christine, B. J. natn. Canc. Inst. 1973, 50, 1107. 23. Hughes, D. Nature, 1977, 226, 405. 24. Svalgaard, L., Wilcox, J. ibid. 1976, 262, 7 60. 25. Ruderman, M. A., Foley, H. M., Chamberlain, J. W. Science, 1976, 191, 555. 26. Environmental Impact of Stratospheric Flight. Natn. Acad. Sci. U.S.A.,
Washington, D.C., 1975.
Occasional
Survey
INCREASED INCIDENCE OF MALIGNANT MELANOMA AFTER PEAKS OF SUNSPOT ACTIVITY ALAN HOUGHTON EDWARD W. MUNSTER MICHAEL V. VIOLA
Oncology Division, Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut 06032, U.S.A.
Summary
age-adjusted incidence-rate for malignant melanoma in the State of The
Connecticut has risen from 1·1 per 100 000 individuals in 1935 to 6·2 per 100 000 individuals in 1975. Superimposed on a steady rise in incidence are 3-5 year periods in which the rate of increase in incidence rises. These periods have a cycle of 8-11 years and follow times of maximum sunspot activity.
Year incidence of malignant melanoma in the State of Connecticut per 100 000 persons.
Age-adjusted -
=males and females; -=males alone. Arrows indicate the
peak of sunspot activity. INTRODUCTION
THE aetiology of melanoma is complex and may include the influences of trauma, heredity, and hormonal activity. Several observations suggest that solar radiation may also have a role; melanoma is more common in fair-skinned individuals2 and is most frequent at skinsites exposed to the sun,3and in white populations is more common in areas closer to the equator4,5 where the intensity of solar radiation is higher. Data from various parts of the world suggest that the incidence of melanoma is increasing6,7 and several reviewers5,7,8 support this view. We have reviewed data from the Connecticut Tumor Registry-which has the longest record of State population-based cancer statistics in the United States-in an attempt to define more precisely the increasing incidence-rates in this state. METHODS
2983 cases of histologically proven melanoma registered in the Connecticut Tumor Registry in 1935-74 were reviewed. Methods of data collection and statistical analysis were published previously.9 The statistical package for social scienceslO was used on a ’Univac 1106’ computer for calculating correlations and regressions. Incidence curves were smoothed by the 3RSSH,2 method of Tukey. II Relative sunspot numbers were obtained from Waldmeirl2 and Eddy."
This cyclic pattern of melanoma incidence led us to attempt correlations with other cyclic events, the most obvious being the sunspot cycle (see figure). Each period in which the incidence of melanoma rose sharply began at the peak of a sunspot cycle and persisted for 3-5 years before falling. The most recent rise in incidence, which began in the mid-1960s, was the greatest but in 1975 had yet to form a plateau. The secular increase in the incidence of melanoma can be represented by a linear regression equation relating melanoma (non-smoothed, age-adjusted incidencerates) to time over three sunspot cycles (33 years). This correlation coequation has a significant (P<0-01) efficient (0-9327). The independent effect of sunspot cycles was examined by calculating the deviation from the regression equation-i.e., removing the effect of increasing rates with time. The deviations from the linear regression line were cyclic. We calculated the partial correlations of annual sunspot numbers with melanoma incidence, controlling for the linear time effect and found statistically significant partial correlations between the sunspot number and the melanoma incidence-rates in each of the subsequent three years, the closest association being that with the incidence two years later (table I). Data from cancer registries in New York State,14 Nor-
RESULTS TABLE I-PARTIAL CORRELATION COEFFICIENTS RELATING
The age-adjusted incidence-rate of melanoma in Connecticut rose from 1-11 per 100 000 individuals in 19355 to 6.2 per 100 000 individuals in 1975 (see figure). The incidence-rate doubled between 1950 and 1975. Superimposed on a steady rise in incidence over forty years were periods during which the rise in incidence became more acute, reaching a peak in 3-5 years, before returning to the baseline rates of increase. Between 1935 and 1975 this cycle occurred four times, with 8-11 year
intervals.
ANNUAL SUNSPOT NUMBER TO MELANOMA INCIDENCE
p
values are shown in parentheses.
N.s.=not
significant.
(1935-67)
760 TABLE II-PARTIAL CORRELATION COEFFICIENTS RELATING ANNUAL SUNSPOT NUMBER TO MELANOMA INCIDENCE
p-values are shown in parentheses.
rt.s.=not
1950-71
significant.
and Finland16 for 1950-71 were analysed in a similar way. In New York State, like Connecticut, there were significant partial correlations between the annual sunspot number and the melanoma incidence-rates in the subsequent 1-2 years (table II). A different pattern was observed in Finland where the increased incidencerates were significantly correlated with the years of sunspot activity and with the first subsequent year.
way,"
DISCUSSION
Two independent variables affect the incidence of melanoma in Connecticut-a linear increase with time, which has been observed by other investigators,7 and cyclic increases which lag approximately two years after sunspot activity. We were unable to correlate the cyclic increases in the incidence of melanoma with any major economic oscillations, variations in dressing behaviour, or mores. It is unlikely that the cycles are related to census timing (every ten years) since the population at risk is estimated retrospectively for non-census years by trend lines9 and the cyclic increases in the incidence of melanoma occur randomly in relation to census years. There is no cyclic pattern in data from the Connecticut Tumor Registry on the incidence of cancer of the stomach,17 cervix,t8 endometrium,19 breast, 20 colorectum,21 lung,21 or in the incidence of Hodgkin’s disease.22 A cyclic pattern of similar type was detected in data from New York State and Connecticut although no such relationship was established in data from Norway. The lag period between sunspot cycles and the cyclic increases in the incidence of melanoma was longer in Connecticut than in Finland. This effect may be latitudinal and could be important in constructing a mechanism of
sunspot-induced carcinogenesis. The sunspot phenomenon has a complex relationship to other geophysical and astrophysical events.23,24 Modification of the solar wind magnetic fields associated with sunspot cycles can influence galactic cosmic rays entering the stratosphere. The increased collisions between cosmic rays and stratospheric particles generate free nitrogen atoms and negative ions, both of which can catalyse the destruction of stratospheric ozone.25 Stratospheric ozone absorbs potentially carcinogenic ultraviolet radiation (U.V.-B.) (290-320 nm), limiting the amount reaching the earth’s surface. The reduction of stratospheric ozone associated with sunspot cycles ismost prominent at the polar caps but, with time, can diffuse to lower latitudes. Thus, the lag period between sunspot cycles and the cyclic increases in the incidence
of melanoma in areas at higher latitudes might be expected to be shorter than in
(e.g., Finland) areas at
lower
latitudes (e.g., Connecticut). Evidence for the role of u.v.-B. in the aetiology of’ melanoma has been summarised in the report of the Climatic Impact Committee of the National Academy of Sciences26 which contains several models (interpolation formulas) relating stratospheric ozone reduction and U.V.-B. flux at the earth’s surface to the incidence of melanoma. The rate of increase in melanoma in Connecticut following sunspot cycles (e.g., 1946-1949, 1957-1960) exceeds that predicted by these models. The ozone reduction associated with sunspot cycles is 1-3%. However the incidence of melanoma may be influenced by other variables which affect u.v.-B. flux at the earth’s surface,26 as well as by other carcinogens, outdoor recreational habits, and the susceptibility of individuals within the population. Requests for reprints should be addressed to M. V. V., Oncology Division, Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut 06032, U.S.A. REFERENCES 1. 2. 3. 4.
Lee, J. A. H. in Progress in Clinical Cancer; p. 151 New York, 1975. Lancaster, H., Nelson, J. Med. J. Aust. 1957, i, 452. Davis, N. C., Herron, J. J., McLeod, G. R. Lancet, 1966, ii, 407. Elwood, J. M., Lee, J. A. H., Walter, S. D., Mo, T., Green, A. Int. J. Epi-
demiol. 1974, 3, 325. 5. Magnus, K. Cancer, 1973, 32, 1275. 6. Burbank, F. in Patterns of Cancer Mortality in the United States 1950-1967. N n. Cancer Inst. Monograph; p. 33, 1971. 7. Lee, J. A. H., Carter, A. P. J. Cancer Inst. 1970, 45, 91. 8. Viola, M. V., Houghton, A. Conn. Med. (in the press). 9. Eisenberg, N., Campbell, P:, Flannery, J. Cancer in Connecticut 1935-1962. Connecticut State Department of Health. Hartford, 1967. 10. Nie, W., Hull, C., Jenkins, J., Steinbrenner, K., Bent, D. Statistical Package for Social Sciences. New York, 1975. 11. Tukey, J. Exploratory Data Analysis; p. 523. Reading, Massachusetts, 1977. 12. Waldmeir, M. W. Sunspot Activity in Zurich, 1610-1960. Zurich, 1961. 13. Eddy, J. Science, 1976, 192, 1189. 14. Greenwald, P., and others. Cancer Incidence and Mortality in New York State. Bureau of Cancer Control, New York State Department of Health, 1976. 15. The Cancer Registry of Norway. Trends in Cancer Incidence in Norway, 1955-1967. Oslo, 1972. 16. Finnish Cancer Registry: Cancer Incidence in Finland. Cancer Society of Finland. Helsinki, 1965-1976. 17. Nonoz, N., Connelly, R. Int. J. Cancer, 1970, 8, 164. 18. Christine, B., Chapple, M., Nadeau, D. Conn. Med. 1972, 36, 669. 19. Cramer, D., Cutler, S. J., Christine, B. Gynec. Oncol. 1970, 2, 130. 20. Cutler, S. J., Connelly, R. Cancer, 1964, 23, 767. 21. Houghton, A., Munster, E. W., Viola, M. V. Unpublished. 22. Krypico, F., Myers, M., Prusiner, S., Heise, H., Christine, B. J. natn. Canc. Inst. 1973, 50, 1107. 23. Hughes, D. Nature, 1977, 226, 405. 24. Svalgaard, L., Wilcox, J. ibid. 1976, 262, 7 60. 25. Ruderman, M. A., Foley, H. M., Chamberlain, J. W. Science, 1976, 191, 555. 26. Environmental Impact of Stratospheric Flight. Natn. Acad. Sci. U.S.A.,
Washington, D.C., 1975.