The Science of the Total Environment, 116 (1992) 243-251 Elsevier Science Publishers B.V., Amsterdam
243
Geochemical prospection of cadmium in a high incidence area of prostate cancer, Sierra de Gata, Salamanca, Spain A. G a r c i a Sfinchez a, J.F. A n t o n a a a n d M. U r r u t i a b ~Department of Mineralogy and Geochemistry. 1.R.N.A.-C.S.1. C., Aptdo 257, Salamanca and bDepartment of Urology, Faculty of Medicine, University of Salamanca, Salamanca, Spain (Received November 8th, 1990; accepted May 26th, 1991)
ABSTRACT A high incidence of prostate cancer was observed in some areas of Salamanca province, Spain. After excluding the most common etiological factors as the cause, it is concluded that the only possible risk factor must be due to the presence of some environmental carcinogen. In view of the etiological relationship between Cd and the pathological state, a study was carried out on the geochemistry of this element in the area. Anomalous amounts of Cd were found in stream sediments. This anomaly does not correspond to human activity, but rather to high regional amounts of cadmium in the substrate. Thus, the contents of Cd in soils developed over substrates containing naturally-occurring anomalous amounts of cadmium and the concentration in underground waters should be considered as a risk factor in this area.
Key words." geochemistry; cadmium; prostate cancer; Spain
INTRODUCTION In a p r e v i o u s e p i d e m i o l o g i c a l s t u d y on p r o s t a t e c a n c e r c a r r i e d o u t in the p r o v i n c e o f S a l a m a n c a (Spain) b y M a y o r a n d U r r u t i a [1] a clear pred o m i n a n c e o f the disease in the rural e n v i r o n m e n t w a s o b s e r v e d w h e n c o m p a r e d to the u r b a n setting. T h e relative risk a s s o c i a t e d with different exp o s u r e factors: a l c o h o l abuse, excessive s m o k i n g , e x p o s u r e to p o t e n t i a l l y toxic s u b s t a n c e s , p r e v i o u s infection, a p r e v i o u s family h i s t o r y o f cancer, age, c o n s a n g u i n i t y , v e n e r e a l disease a n d the s o c i o - e c o n o m i c status o f the p o p u l a tion w h e r e calculated. T h e analysis o f the p o p u l a t i o n s t r u c t u r e b y age g r o u p s (Fig. 1) s h o w s a S a w y index o f 0.88, w h i c h is clearly illustrative o f a n a g e d s t r u c t u r e o f the p o p u l a t i o n , if c o m p a r e d with the figures given f o r the w h o l e 0048-9697/92/$05.00
© 1992 Elsevier Science Publishers B.V. All rights reserved
244
A. GARCIA S,~NCHEZ ET AL.
>75 7O - 74 65 69 60 - 64
::::::::::::::::::::::::::::::: ET......:..,:.:.:.....
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:::::::::::::::::::::::::::::: ~:i:iii:i~ii~:[~L~Li:ii~ii:iiiili[i:ii:] It~tt~;tt~ttttt~t~t~t~i~t~t~tt;;ttt; t;;t;~i 15 - 19
li!~t~tti~ii~i~i~t~i~ttti~ii~t~ii~i~iiii~ii~i!~ii~i~i~ti~i]~ii~ti~l0-4 10
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WORLDSTANDAnTPO~LATION
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:'!:!il
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10
PROVINCE O F ~ M . , , , N ~
Fig. l. Pinetree chart showing the age structure by age groups of world standard (WHO,
population versus Province of Salamanca (Instituto Nacional de estadistica, 1990).
country (0.55) and the world standard population (0.27) (WHO, 1978). The mortality rate from prostate cancer in Spain, based on official mortality certificates, was 12.7% in 1966-1970; England, Ireland and Portugal had similar rates [2]. Therefore, from the epidemiologic point of view, the age of the population seems to be the decisive factor modulating the high incidence rates of prostate cancer in our area, since neither the prevalence of incidental prostate tumors found in autopsies or suprapubic prostatectomy specimens, nor the influence of other possible, yet controversial etiologic factors, such as dietary fat intake levels, significantly differs in our series from those reported in other developed countries. One of the most important conclusions of that study was the absence of any significant statistical association between exposure to the different toxic substances employed in rural activities and the incidence of prostate cancer. This finding suggested that some types of environmental carcinogens [1] might be involved. It is currently accepted that there is a relationship between cadmium and this disease [3,4], hence we carried out a study on the geochemical distribution of Cd in zones with a high incidence of prostate cancer. Since the absorption of cadmium by the body is low [5] and because intestinal and urinary elimination of the element is also slow [6], it accumulates in body tissues [7,8]; more explicitly, in those tissues containing
245
C A D M I U M AS AN E N V I R O N M E N T A L C A R C I N O G E N
high levels of Zn, for which it is able to substitute [9]. In this context, the epithelium of the prostate gland contains eight times more Zn than other body tissues [10]. A zone with a particularly high incidence of prostate cancer is the Sierra de Gata [1] in the province of Salamanca (Spain). This zone was chosen to carry out a geochemical exploration study on Cd in water course sediments. Geologically, the central and eastern parts of the zone contain metamorphic rocks (Fig. 2) belonging to the Grauwack-Schist Complex [12]. Two units are distinguishable: the lower unit, composed of conglomerates, porphyroids and quartzites, mainly to the south and the upper unit, formed of black slates, limestones, conglomerates and quartzites, mainly to the north. The western part is mainly composed of igneous rocks (granites, pegmatites, aplites and quartz veins). In such circumstances, the best geochemical method to stimate the Cd levels in the region is a stream sediments exploration.
E7 :
I
I 4
*
6
.: ji! fili iii o
T ~
! ....
÷:;1:::7::::::'" ,o+ . . . . . . . . . °*****
, .*" .1"~
................
. p.
/
Fig. 2. Generalized geological map of the Sierra de Data area (Salamanca, Spain). Modified from Garcia de Figuerola [111 and Rodriguez [12]. (1) Undeformed Terciary and Ouaternary units; (2) Silurian and Ordovician rocks; (3) Precambrian and Cambrian rocks. GrauwackSchist Complex (Superior unit). (4) Precambrian rocks. Grauwack Schist Complex (Inferior unit). (5) Calco-alcaline granites. (6) Alcaline granites.
246
A. GARC~A S,~NCHEZ ET AL
TABLE 1 Concentrations in p p m o f analyzed elements from stream sediments Sample number 21 24 25 28 29 43 45 55 56 59 60 63 70 72 81 82 85 92 93 110 112 148 156 157 159 162 165 166 167 168 169 172 173 175 177 177 bis 178 179 180 181 187 188 188 bis 202
As
Pb
Cd
Zn
< < < < < < < < < < < < < < < < < < < <
1.7/1000 are high values in this area [11.
The findings of the present study show that even though we cannot unequivocally demonstrate that Cd is the determining factor for the cause of prostate cancer, this element could play an important role with its presence near areas where the incidence of cancer is high. Additionally, since the anomalies in cadmium levels are not due to human activity, but rather to a naturally occurring excess of the element in the local soils, it should be included as a risk factor in cancer prostate in all epidemiological studies on cadmium in this area, because the most c o m m o n etiological factors have been excluded [1]. To prove this hypothesis it would be necessary to analyse drinking water, the local milk and vegetables produced in the areas. REFERENCES 1
F.J. Mayor and M. Urrutia, Epidemiologia del c~incer de pr6stata en Salamanca, (Espafia). Universidad de Salamanca, Salamanca, 1988.
C A D M I U M AS AN E N V I R O N M E N T A L C A R C I N O G E N
2
3 4 5
6
7 8
9 10 11 12 13 14 15 16 17
18
19 20 21 22 23
251
J. Banus, Epidemiologia y Etiologia del Cfincer de Prostata. In Tratamiento Actual del Carcinoma de Prostata. Receptores Hormonales. XLVI Congreso Nacional de Urologia. Jaca, 1981. R. Lemen, J. Lee and Wagoner, Cancer mortality among ethnics subgroups of the white population of New York. J. Ann N.Y. Acad. Sci., 271 (1976) 273-279. A. McMichael, Mortality among Rubber Workers: Relationship to specific works. J. Ocup. Med., 18 (1976) 178-185. T. Rahola, R.K. Aaran and J.K. Miettinen, Half-time studies of mercury and cadmium by whole body counting. In Assessment of radioactive contamination in man. Int. At. Energy Agency, Vienna (1972). P.D. Whanger, Factors affecting the metabolism of Nonessential Metals in Food, in J.N. Hathcock, (Ed.), Nutritional Toxicology, Vol. I. Academic Press, New York, 1980, pp. 164-202. A. Garcia Sanchez, Cadmio y medio ambiente. Rev. Tecn. Med. Ambiente, 8 (1989) 105-109. W.J. Miller, D.M. Blackman, R.P. Gentry and F.M. Pate, Effect of dietary cadmium on tissue distribution of cadmium following a single oral dose in young goats. J. Dairy Sci., 52 (1969) 2029-2035. J.T. Deagen, S.H. Oh and P.D. Wanger, Biological function of metallothionein. V1. Interaction of cadmium and zinc. Biol. Trace. Elem. Res., 2 (1980) 65-80. W.F. Whitmore, Comments on zinc in the human and canine prostates. Nat. Cancer Inst. Mon., 12 (1963) 337. J.L. Garcia de Figuerola, Sintesis Geol6gica del Basamento (Zona del Centro-Oeste Espafiol), sscale 1:200.000. Universidad de Salamanca, Salamanca, 1983. M.D. Rodiguez, E1 Complejo Esquisto-Grauv~quico y el paleozoico en el Centro-Oeste Espaik, Acta Salmanticensia 51. Universidad de Salamanca, Salamanca, 1985. W.A. Rose, H.E. Hawkes and J.S. Webb, Geochemistry in Mineral Exploration. Academic Press, London, 1979. K. Govindaraju, Compilation of working values and sample description for 272 geostandars. Geostandards Newsletter 13, Special issue (1989) 113. E.S. Gladney, E.A. Jones and E.J. Nickeld, 1988 Completion of element concentration data for USGS Basalt BCR-I. Geostandards Newsletter, 14 (1990) 209-360. B. Brehler, H. Wakita and R.A. Schmitt, Cadmium, in K.H. Wedepohl (Ed.), Handbook of Geochemistry. Springer, Berlin, 1978, pp. 48-A-1 to 48-0-1. R. Boluda, V. Andreu, V. Pons and J. Sanchez, Contenido de metales pesados (Cd, Co, Cr, Cu, Ni, Pb Y Zn) en suelos de la comarca La Plana de Requena-Utiel (Valencia). An. Edafol. Agrobiol. (1989) 1485-1502. V. Cala, J. Rodriguez and A. Guerra, Contaminaci6n por metales pesados en suelos de la Vega de Aranjuez. (I) Pb, Cd, Cu, Zn Ni y Cr. An. Edafol. Agrobiol. (1985) 1595-1608. A. Kabata-Pendias and H. Pendias, 1984. Trace elements in soils and plants. CRS Press Inc. Boca Raton, Florida, 315 p. M.R.S. Fox, Nutritional influences on metal toxicity: Cadmium as a model toxic element. Environ. Health Perspect., 29 (1979) 95-104. W.H.O., Euro. Reports and Studies, 61, ICP/RCE 101. World Health Organization, (1982). J.V. Lagerwerff and A.W. Specht, Contamination of roadside soil and vegetation with cadmium, nickel, lead and zinc. Environ. Sci. Technol., 4 (1970) 583-586. K. Tsuchiya, Epidemiological studies on cadmium in the environtment in Japan: Etiology of Itai-Itai disease. Fed. Proc., Fed. Am. Soc. Exp. Biol., 35 (1976) 2412-2418.
243
Geochemical prospection of cadmium in a high incidence area of prostate cancer, Sierra de Gata, Salamanca, Spain A. G a r c i a Sfinchez a, J.F. A n t o n a a a n d M. U r r u t i a b ~Department of Mineralogy and Geochemistry. 1.R.N.A.-C.S.1. C., Aptdo 257, Salamanca and bDepartment of Urology, Faculty of Medicine, University of Salamanca, Salamanca, Spain (Received November 8th, 1990; accepted May 26th, 1991)
ABSTRACT A high incidence of prostate cancer was observed in some areas of Salamanca province, Spain. After excluding the most common etiological factors as the cause, it is concluded that the only possible risk factor must be due to the presence of some environmental carcinogen. In view of the etiological relationship between Cd and the pathological state, a study was carried out on the geochemistry of this element in the area. Anomalous amounts of Cd were found in stream sediments. This anomaly does not correspond to human activity, but rather to high regional amounts of cadmium in the substrate. Thus, the contents of Cd in soils developed over substrates containing naturally-occurring anomalous amounts of cadmium and the concentration in underground waters should be considered as a risk factor in this area.
Key words." geochemistry; cadmium; prostate cancer; Spain
INTRODUCTION In a p r e v i o u s e p i d e m i o l o g i c a l s t u d y on p r o s t a t e c a n c e r c a r r i e d o u t in the p r o v i n c e o f S a l a m a n c a (Spain) b y M a y o r a n d U r r u t i a [1] a clear pred o m i n a n c e o f the disease in the rural e n v i r o n m e n t w a s o b s e r v e d w h e n c o m p a r e d to the u r b a n setting. T h e relative risk a s s o c i a t e d with different exp o s u r e factors: a l c o h o l abuse, excessive s m o k i n g , e x p o s u r e to p o t e n t i a l l y toxic s u b s t a n c e s , p r e v i o u s infection, a p r e v i o u s family h i s t o r y o f cancer, age, c o n s a n g u i n i t y , v e n e r e a l disease a n d the s o c i o - e c o n o m i c status o f the p o p u l a tion w h e r e calculated. T h e analysis o f the p o p u l a t i o n s t r u c t u r e b y age g r o u p s (Fig. 1) s h o w s a S a w y index o f 0.88, w h i c h is clearly illustrative o f a n a g e d s t r u c t u r e o f the p o p u l a t i o n , if c o m p a r e d with the figures given f o r the w h o l e 0048-9697/92/$05.00
© 1992 Elsevier Science Publishers B.V. All rights reserved
244
A. GARCIA S,~NCHEZ ET AL.
>75 7O - 74 65 69 60 - 64
::::::::::::::::::::::::::::::: ET......:..,:.:.:.....
:::?il
: : : -::
-
t~'~{~!~
::::::::::::::::::::::::::::::::::::::: ~i~.ii~ii~iitii~iiiiii~ii~ii~i!~l 5 0 - 5 4
m~;~:~]
45 - 49
E:i:~:i:i:i:~:i:i~i::~ ~.:-~i-i:iiiil L.-hi:i:i:?:i:~:i:iG~[~[i?i:!:il :::::::::::::::::::t
:::::::::::::::::::::::::::::: ~:i:iii:i~ii~:[~L~Li:ii~ii:iiiili[i:ii:] It~tt~;tt~ttttt~t~t~t~i~t~t~tt;;ttt; t;;t;~i 15 - 19
li!~t~tti~ii~i~i~t~i~ttti~ii~t~ii~i~iiii~ii~i!~ii~i~i~ti~i]~ii~ti~l0-4 10
I
5
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(xl0~)
WORLDSTANDAnTPO~LATION
[:':':':':':':':':':
:':':':
: :" ":':':
:':':
:'!:!il
[i:i:i:!:!:i:]:i:i::.T~:i:] 0 [i~i~:~
5
10
PROVINCE O F ~ M . , , , N ~
Fig. l. Pinetree chart showing the age structure by age groups of world standard (WHO,
population versus Province of Salamanca (Instituto Nacional de estadistica, 1990).
country (0.55) and the world standard population (0.27) (WHO, 1978). The mortality rate from prostate cancer in Spain, based on official mortality certificates, was 12.7% in 1966-1970; England, Ireland and Portugal had similar rates [2]. Therefore, from the epidemiologic point of view, the age of the population seems to be the decisive factor modulating the high incidence rates of prostate cancer in our area, since neither the prevalence of incidental prostate tumors found in autopsies or suprapubic prostatectomy specimens, nor the influence of other possible, yet controversial etiologic factors, such as dietary fat intake levels, significantly differs in our series from those reported in other developed countries. One of the most important conclusions of that study was the absence of any significant statistical association between exposure to the different toxic substances employed in rural activities and the incidence of prostate cancer. This finding suggested that some types of environmental carcinogens [1] might be involved. It is currently accepted that there is a relationship between cadmium and this disease [3,4], hence we carried out a study on the geochemical distribution of Cd in zones with a high incidence of prostate cancer. Since the absorption of cadmium by the body is low [5] and because intestinal and urinary elimination of the element is also slow [6], it accumulates in body tissues [7,8]; more explicitly, in those tissues containing
245
C A D M I U M AS AN E N V I R O N M E N T A L C A R C I N O G E N
high levels of Zn, for which it is able to substitute [9]. In this context, the epithelium of the prostate gland contains eight times more Zn than other body tissues [10]. A zone with a particularly high incidence of prostate cancer is the Sierra de Gata [1] in the province of Salamanca (Spain). This zone was chosen to carry out a geochemical exploration study on Cd in water course sediments. Geologically, the central and eastern parts of the zone contain metamorphic rocks (Fig. 2) belonging to the Grauwack-Schist Complex [12]. Two units are distinguishable: the lower unit, composed of conglomerates, porphyroids and quartzites, mainly to the south and the upper unit, formed of black slates, limestones, conglomerates and quartzites, mainly to the north. The western part is mainly composed of igneous rocks (granites, pegmatites, aplites and quartz veins). In such circumstances, the best geochemical method to stimate the Cd levels in the region is a stream sediments exploration.
E7 :
I
I 4
*
6
.: ji! fili iii o
T ~
! ....
÷:;1:::7::::::'" ,o+ . . . . . . . . . °*****
, .*" .1"~
................
. p.
/
Fig. 2. Generalized geological map of the Sierra de Data area (Salamanca, Spain). Modified from Garcia de Figuerola [111 and Rodriguez [12]. (1) Undeformed Terciary and Ouaternary units; (2) Silurian and Ordovician rocks; (3) Precambrian and Cambrian rocks. GrauwackSchist Complex (Superior unit). (4) Precambrian rocks. Grauwack Schist Complex (Inferior unit). (5) Calco-alcaline granites. (6) Alcaline granites.
246
A. GARC~A S,~NCHEZ ET AL
TABLE 1 Concentrations in p p m o f analyzed elements from stream sediments Sample number 21 24 25 28 29 43 45 55 56 59 60 63 70 72 81 82 85 92 93 110 112 148 156 157 159 162 165 166 167 168 169 172 173 175 177 177 bis 178 179 180 181 187 188 188 bis 202
As
Pb
Cd
Zn
< < < < < < < < < < < < < < < < < < < <
1.7/1000 are high values in this area [11.
The findings of the present study show that even though we cannot unequivocally demonstrate that Cd is the determining factor for the cause of prostate cancer, this element could play an important role with its presence near areas where the incidence of cancer is high. Additionally, since the anomalies in cadmium levels are not due to human activity, but rather to a naturally occurring excess of the element in the local soils, it should be included as a risk factor in cancer prostate in all epidemiological studies on cadmium in this area, because the most c o m m o n etiological factors have been excluded [1]. To prove this hypothesis it would be necessary to analyse drinking water, the local milk and vegetables produced in the areas. REFERENCES 1
F.J. Mayor and M. Urrutia, Epidemiologia del c~incer de pr6stata en Salamanca, (Espafia). Universidad de Salamanca, Salamanca, 1988.
C A D M I U M AS AN E N V I R O N M E N T A L C A R C I N O G E N
2
3 4 5
6
7 8
9 10 11 12 13 14 15 16 17
18
19 20 21 22 23
251
J. Banus, Epidemiologia y Etiologia del Cfincer de Prostata. In Tratamiento Actual del Carcinoma de Prostata. Receptores Hormonales. XLVI Congreso Nacional de Urologia. Jaca, 1981. R. Lemen, J. Lee and Wagoner, Cancer mortality among ethnics subgroups of the white population of New York. J. Ann N.Y. Acad. Sci., 271 (1976) 273-279. A. McMichael, Mortality among Rubber Workers: Relationship to specific works. J. Ocup. Med., 18 (1976) 178-185. T. Rahola, R.K. Aaran and J.K. Miettinen, Half-time studies of mercury and cadmium by whole body counting. In Assessment of radioactive contamination in man. Int. At. Energy Agency, Vienna (1972). P.D. Whanger, Factors affecting the metabolism of Nonessential Metals in Food, in J.N. Hathcock, (Ed.), Nutritional Toxicology, Vol. I. Academic Press, New York, 1980, pp. 164-202. A. Garcia Sanchez, Cadmio y medio ambiente. Rev. Tecn. Med. Ambiente, 8 (1989) 105-109. W.J. Miller, D.M. Blackman, R.P. Gentry and F.M. Pate, Effect of dietary cadmium on tissue distribution of cadmium following a single oral dose in young goats. J. Dairy Sci., 52 (1969) 2029-2035. J.T. Deagen, S.H. Oh and P.D. Wanger, Biological function of metallothionein. V1. Interaction of cadmium and zinc. Biol. Trace. Elem. Res., 2 (1980) 65-80. W.F. Whitmore, Comments on zinc in the human and canine prostates. Nat. Cancer Inst. Mon., 12 (1963) 337. J.L. Garcia de Figuerola, Sintesis Geol6gica del Basamento (Zona del Centro-Oeste Espafiol), sscale 1:200.000. Universidad de Salamanca, Salamanca, 1983. M.D. Rodiguez, E1 Complejo Esquisto-Grauv~quico y el paleozoico en el Centro-Oeste Espaik, Acta Salmanticensia 51. Universidad de Salamanca, Salamanca, 1985. W.A. Rose, H.E. Hawkes and J.S. Webb, Geochemistry in Mineral Exploration. Academic Press, London, 1979. K. Govindaraju, Compilation of working values and sample description for 272 geostandars. Geostandards Newsletter 13, Special issue (1989) 113. E.S. Gladney, E.A. Jones and E.J. Nickeld, 1988 Completion of element concentration data for USGS Basalt BCR-I. Geostandards Newsletter, 14 (1990) 209-360. B. Brehler, H. Wakita and R.A. Schmitt, Cadmium, in K.H. Wedepohl (Ed.), Handbook of Geochemistry. Springer, Berlin, 1978, pp. 48-A-1 to 48-0-1. R. Boluda, V. Andreu, V. Pons and J. Sanchez, Contenido de metales pesados (Cd, Co, Cr, Cu, Ni, Pb Y Zn) en suelos de la comarca La Plana de Requena-Utiel (Valencia). An. Edafol. Agrobiol. (1989) 1485-1502. V. Cala, J. Rodriguez and A. Guerra, Contaminaci6n por metales pesados en suelos de la Vega de Aranjuez. (I) Pb, Cd, Cu, Zn Ni y Cr. An. Edafol. Agrobiol. (1985) 1595-1608. A. Kabata-Pendias and H. Pendias, 1984. Trace elements in soils and plants. CRS Press Inc. Boca Raton, Florida, 315 p. M.R.S. Fox, Nutritional influences on metal toxicity: Cadmium as a model toxic element. Environ. Health Perspect., 29 (1979) 95-104. W.H.O., Euro. Reports and Studies, 61, ICP/RCE 101. World Health Organization, (1982). J.V. Lagerwerff and A.W. Specht, Contamination of roadside soil and vegetation with cadmium, nickel, lead and zinc. Environ. Sci. Technol., 4 (1970) 583-586. K. Tsuchiya, Epidemiological studies on cadmium in the environtment in Japan: Etiology of Itai-Itai disease. Fed. Proc., Fed. Am. Soc. Exp. Biol., 35 (1976) 2412-2418.
