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Published in the Journal of Environmental Pathology, Toxicology and Oncology

AN ECOLOGIC STUDY OF CANCER INCIDENCE RATES

AND ENVIRONMENTAL FACTORS


ABSTRACT

Objective: The environmental factors latitude, temperature and water consumption have been correlated with cancer incidence rates. To date there is no consensus of opinion that explains how these environmental factors alter the incidence of cancer. A fluoride belt stretches across the north and east of Africa, through the middle east, across Pakistan and India, into Southeast Asia and the south of China. There appears to be an association between areas with low cancer incidence rates and high fluoride concentrations in the water supply. This ecologic study attempts to determine if fluoride is correlated with cancer incidence rates, and if so, how fluoride might be a factor in the correlation between latitude, temperature and cancer incidence rates. Method: Population groups with very high cancer incidence rates and population groups with very low cancer incidence rates are compared in an effort to identify environmental factors that might explain the correlation between cancer incidence rates and the environmental factors latitude, temperature and fluoride. Results: There is a correlation between cancer incidence rates and latitude (r = 0.71). There is an inverse correlation between cancer incidence rates and temperature (r = -0.87). There is an inverse correlation between cancer incidence rates and fluoride concentration in the drinking water (r = -0.75). Very low cancer incidence was found in areas with high fluoride concentrations in the drinking water. Conclusions: There is an inverse correlation between the amount of fluoride in the drinking water and cancer incidence rates.

Title: An Ecologic Study of Cancer Incidence Rates and Environmental Factors

KEYWORDS: cancer incidence, latitude, temperature, water consumption, fluoride

INTRODUCTION

The correlation between latitude and cancer incidence rates is well established and has been recognized for many years. A number of explanations have been proposed for the effect of latitude on cancer incidence rates but no explanation has received widespread acceptance. Increased solar radiation in lower latitudes with the associated increased production of vitamin D has been correlated with a reduction in cancer incidence rates.1 However, a recent publication found no correlation between cancer incidence rates and solar radiation.2

In a study on the relationship of latitude and pancreatic cancer Kato et al reported a strong correlation between latitude and pancreatic cancer mortality and a strong inverse correlation with the average temperature.3 In Japan he found there was no difference between urban and rural pancreatic cancer mortality even thought there was a much higher fat intake in large cities. He concluded that there remains the possibility that factors related to latitude or average temperature other than diet may be involved in the occurrence of pancreatic cancer.

Two studies provide evidence that increased water consumption reduces bladder and colorectal cancer. Michaud et al studied the incidence of bladder cancer in 47,909 individuals over a 10-year period.4 They found that daily fluid intake was inversely correlated with the risk of bladder cancer. In conclusion they stated that a high fluid intake is associated with a decreased risk of bladder cancer in men. In a hospital based case-control study Tang et al found a strong inverse correlation between water intake and rectal cancer among men.5 The same trend was found for women but was not significant.

Many carcinogens have been identified that produce an increased incidence of cancer.6 The discovery that fluoride reduces the incidence of caries was made in the early 1900’s.7 By the 1950’s municipal water departments were beginning to add fluoride to the water supply.7 As water was being fluoridated concerns that fluoride is carcinogenic were being voiced. This concern lead to studies to determine if fluoride in the drinking water is related to an increase in cancer incidence rates.9

In 1974 Nixon and Carpenter published a paper comparing standardized mortality ratios in relation to the amount of fluoride in the drinking water.8 They reported finding a statistically significant negative correlation between the standardized mortality rate and the fluoride content of the water. They concluded that all indications were that naturally occurring fluoride was likely to reduce cancer incidence. Hoover et al studied site-specific cancer mortality in Texas counties classified into four groups by fluoride concentration of the drinking water.9 Consistent trends were found for cancers of the buccal cavity, pharynx (males only) esophagus (males and females) and skin cancer (females). All trends indicated a reduction in cancer incidence with increased fluoride concentration. Multiple regression analysis revealed a statistically significant inverse correlation with the fluoride variable in four out of 64 tests of significance. Doll and Kinlen studied cancer incidence between 1950 and 1970 in cities with fluoridated water and in cities without fluoridation. When account was taken for age, sex, and ethnic group the ratio between observed cancer mortality and expected cancer mortality fell slightly in the cities with fluoridated water and did not change in the non-fluoridated cities.10

Mcguire et al in a case-control study of osteosarcoma patients found an inverse correlation between fluoride concentration and the incidence of osteosarcoma.11 In 1995 Gelberg et al published a case-control study comparing fluoride exposure and childhood osteosarcoma.12 They found a statistically significant correlation between increased fluoride intake and a decrease in the incidence of osteosarcoma for males. They proposed that fluoride might have a protective effect for males.

In the 1970’s a series of studies were carried out on normal cells treated with various agents known to initiate mutations by inducing chromosomal damage. Vogel reported a strong antimutagenic effect of fluoride on mutation induced by Trenimon and 1-phenyl-3,3-dimethyltriazene in Drosophila.13 In 1973 Obe and Slacik-Erben reported findings similar as Vogel and proposed that sodium fluoride exerts its antimutagenic action by suppressing events leading to chromosomal breakage.14 In 1976 Slacik-Erben et al reported that chromosomal aberrations induced by Trenimon revealed that pre, simultaneous and post-treatments of sodium fluoride significantly enhanced the frequency of undamaged mitosis.15 They interpreted their findings as an indication that sodium fluoride had significant antimutagenic activity.

Hirano et al studied the effects of fluoride on cultures of the osteosarcoma cell line UMR 106. The addition of 0.5 mM fluoride resulted in the induction of apoptosis and a decrease in cell proliferation.16 Anuradha et al reports that fluoride causes cell death in human leukemia (HL-60) cells by the activation of caspase-3 which in turn cleaves poly(ADP-ribose) polymerase leading to apoptosis.17

Endemic fluorosis is a disease caused by high fluoride consumption resulting from high concentrations of fluoride in drinking water or food.18 Endemic fluorosis is identified by mottling of the teeth. Skeletal fluorosis can develop in areas with very high fluoride concentrations in the drinking water. In fluorosis, the fluoride ion replaces hydroxyl ions in bone apatite.19

Endemic fluorosis and the associated elevated fluoride in drinking water forms a fluoride belt which stretches across the north and east of Africa, through the middle east, across Pakistan and India, into Southeast Asia and the south of China. In many areas on this belt endemic skeletal fluorosis has become a major health issue requiring defluoridation of the drinking water. When plotted on the world map there appears to be an association between endemic fluorosis and reduced cancer incidence rates. The presence of endemic fluorosis allows us to identify areas with very high levels of fluoride in the drinking water. This ecologic study compares latitude, temperature and the fluoride concentration in the drinking water supply for areas with very high cancer incidence rates and areas with very low cancer incidence rates in an effort to determine if cancer incidence rates are correlated with latitude, temperature and fluoride concentration.

MATERIALS / METHODS

Cancer incidence in five continents Vol. VII.20 was used as a reference to form the comparison groups very high cancer incidence rate and very low cancer incidence rate. Age-standardized rates for all sites but 173 was chosen because many cancer reporting stations do not fully report squamous cell and basal cell carcinoma of the skin.21

The very high cancer incidence rate group includes those cancer-reporting stations with a male cancer incidence rate over 300 per 100,000 and a female cancer incidence rate over 250 per 100,000 (Table 1). The cancer incidence rate for males and females was added together to provided a total cancer incidence rate for each reporting station. The very low cancer incidence rate group includes cancer-reporting stations with male and female cancer incidence rates under 160 per 100,000 (Table 2). Again the cancer incidence rate for males and females was added together to provided a total cancer incidence rate.

TABLE 1
VERY HIGH CANCER INCIDENCE RATE GROUP

Age-standardized cancer incidence rate per 100,000 population.20

Location Male Fem. Total
San Francisco, Black 465 286 751
Detroit, Black 464 278 742
San Francisco, White 408 305 713
Atlanta, Black 450 253 703
New Zealand,Maori 360 340 700
Connecticut, Black 425 273 698
Detroit, White 401 294 695
Hawaii, White 398 295 693
New Orleans, Black 418 271 689
Los Angeles, Black 425 262 687
Seattle 395 290 685
Los Angeles, White 373 304 677
Italy, Trieste 414 256 670
New Orleans, White 389 273 662
Atlanta, White 384 273 657
Uruguay, Montevideo 317 255 626
Central Calif., White 351 271 622
Canada, Yukon 326 295 621
Iowa 348 271 619
New Mexico, White 354 261 615
Canada, Nova Scotia 338 268 606
Canada, Ontario 326 261 587
Canada, Manatoba 325 261 586
Canada, Prince Edward Is 322 260 582
Australia, South 324 251 575
Scotland, West 317 256 573
Austria, Tyrol 313 252 565
Australia, West 312 252 564
Scotland 306 257 563
Canada, British Columbia 307 254 561


TABLE 2
VERY LOW CANCER INCIDENCE RATE GROUP
Age-standardized cancer incidence rate per 100,000 population.20


Location Male Fem. Total
The Gambia* 56 39 95
India, Barshietc. 50 54 104
Senegal, Dakar** 76 75 151
Algeria, Setif 107 67 174
India, Karunagappally 108 80 188
India, Trivandrum 108 86 194
Mali, Bamako 125 90 125
India, Bangalore 98 118 216
Israel, Non-Jews 128 94 222
Singapore, Indian 106 123 229
Kuwait, Kuwaitis 104 126 230
Viet Nam, Hanoi 143 89 232
India, Madras 117 130 247
India, Bombay 131 125 256
Singapore, Malay 145 133 278
Lima, Peru 124 151 275
Thailand, Chiang Mai 144 153 297
New Mexico, Am Indian 151 148 299
Uganda, Kyadondo 155 146 301
* Data from an earlier edition of Cancer incidence in five continents Vol VI 1992
** Data from an earlier edition of Cancer incidence in five continents Vol IV 1982

While there is no organized database for the world’s drinking water supply most nations and many scientific investigations have published data on the world’s drinking water. The fluoride concentration at the same site can very considerably according to whether the water source is surface water, shallow bore wells or deep bore wells. The concentration of fluoride can also very significantly from village to village. For this reason obtaining an exact figure for fluoride concentration in the drinking water for a cancer incidence-reporting station is difficult. Fluoride content in the water is related to geologic formations. Areas located in the same geologic formations will have similar fluoride levels in the ground water supply. For this reason, if a reporting station did not have a published fluoride level the fluoride concentration from an adjoining area was used for comparison.

Cancer incidence, latitude, temperature and fluoride concentration is listed for the very high and very low cancer incidence rate groups (tables 3 and 4). For those cancer-reporting stations with fluoridation the fluoride concentration after the addition of fluoride was used for calculating the correlation coefficient. The average maximum average temperature for the cancer incidence reporting stations was selected because daytime temperature should have the most significant effect on human physiology assuming people are insulated from the effects of nighttime temperatures.

TABLE 3
VERY HIGH CANCER INCIDENCE RATE WITH LATITUDE, TEMPERATURE AND FLUORIDE IN THE DRINKING WATER
Location Total CI20 Lat20 Temp22 Nat. Fl* Fluorosis** Fluoridation
San Francisco, Black 751 38 63 <.4 mg/l -- +23
Detroit, Black 742 42 58 <.4 mg/l -- +23
San Francisco, White 713 38 63 <.4 mg/l -- +23
Atlanta, Black 703 34 72 <.4 mg/l -- +23
New Zealand, Maori 700 40 59 <.4 mg/l -- +23
Connecticut, Black 698 41 60 <.4 mg/l -- +23
Detroit, White 695 42 58 <.4 mg/l -- +23
Hawaii, White 693 22 84 <.4 mg/l -- --24
New Orleans, Black 689 30 78 <.4 mg/l -- +23
Los Angeles, Black 687 34 73 <.4 mg/l -- --25
Seattle 685 47 59 <.4 mg/l -- +23
Los Angeles, White 677 34 73 <.4 mg/l -- --25
Italy, Trieste 670 45 63 <.4 mg/l -- --26
New Orleans, White 662 30 78 <.4 mg/l -- +23
Atlanta, White 657 34 72 <.4 mg/l -- +23
Uruguay, Montevideo 626 35 70 <.4 mg/l -- +23
Central Calif., White 622 36 76 <.4 mg/l -- +23
Canada, Yukon 621 63 40 <.4 mg/l -- +23
Iowa 619 42 60 <.4 mg/l -- +23
New Mexico, White 615 35 70 <.4 mg/l -- +23
Canada, Nova Scotia 606 49 48 <.4 mg/l -- +23
Canada, Ontario 587 45 54 <.4 mg/l +27 +23
Canada, Manatoba 586 49 47 <.4 mg/l -- +23
Canada, Prince Edward Is 582 47 49 <.4 mg/l -- +23
Australia, South 575 35 70 <.4 mg/l -- +23
Scotland, West 573 57 52 <.4 mg/l -- --28
Austria, Tyrol 565 46 57 <.4 mg/l -- --29
Australia, West 564 32 75 <.4 mg/l -- +23
Scotland 563 56 53 <.4 mg/l -- -28
Canada, British Columbia 561 49 56 <.4 mg/l -- +23
* All fluoridated cities have low natural fluoride concentration in the drinking water supply.
** Fluorosis is determined by a citation of fluorosis in the literature.

TABLE 4

VERY LOW CANCER INCIDENCE RATE WITH LATITUDE, TEMPERATURE AND FLUORIDE CONCENTRATION IN THE DRINKING WATER

Location Total CI20 Lat.20 Temp22 Nat.Fl Fluorosis Fluoridation
The Gambia 98* 13 80 10 mg/l 30 +30 --23
Barshi, Paranda, Bhum 104 18 91 10 mg/l 31 +31 --23
Senegal, Dakar 151** 13 80 10 mg/l 30 +30 --23
Algeria, Setif 174 35 72 4.0 mg/l 32 +32 --23
India, Karunagappally 188 9 86 5.1 mg/l 33,34 +34 --23
India, Trivandrum 194 8 87 5.1 mg/l 33,34 +34 --23
Mali, Bamako 215 13 92 10 mg/l 30 +30 --23
India, Bangalore 216 13 83 9.1 mg/l 33,34 +34 --23
Israel, Non-Jews 222 32 69 5.0 mg/l 35 +35 --23
Singapore, Indian 229 1 87 0.7 mg/l 36 +36 +36
Kuwait, Kuwaitis 230 29 90 0.4 mg/l 37 +38 --23
Viet Nam, Hanoi 232 21 80 unknown unknown unknown
India, Madras 247 13 90 3.3 mg/l 39 +39 --23
India, Bombay 256 19 88 .32 mg/l 39 +39 --23
Singapore, Malay 278 1 87 0.7 mg/l 36 +36 +36
Lima, Peru 275 12 73 unknown unknown unknown
Thailand, Chiang Mai 297 16 89 5.0 mg/l 40 +41 --23
New Mexico, Am Indian 299 35 70 4.1 mg/l 42 +42 --23
Uganda, Kyadondo 301 0 79 1.5 mg/l 43 +43 --23
* Data from an earlier edition of Cancer incidence in five continents Vol VI 1992
** Data from an earlier edition of Cancer incidence in five continents Vol IV 1982

RESULTS

The average latitude for the very high cancer incidence rate group is 41 degrees. The average latitude for the very low cancer incidence rate group is 16 degrees. The correlation between the cancer incidence rate and latitude is r = 0.71.

The average maximum average temperature of the very high cancer incidence rate group is 63 degrees F. The average maximum average temperature of the very low cancer incidence rate group is 83 degrees F. The correlation between the cancer incidence rate and temperature is r = -0.87.

The average fluoride concentration of the very high cancer incidence rate group is 0.71 mg/l. The average fluoride concentration of the very low cancer incidence rate group is 5.0 mg/l. The correlation between the cancer incidence rate and the fluoride concentration in the drinking water is r = -0.75.

The very high cancer incidence rate group seldom reported endemic fluorosis. Endemic fluorosis was reported in 17 of 19 very low cancer incidence reporting areas. Information could not be found on the fluoride concentration or the incidence of fluorosis in Hanoi, Viet Nam or Lima, Peru.

Upon review of the available data, fluoride was found in high concentrations in virtually all very low cancer incidence rate areas and was found in low concentrations in all very high cancer incidence rate areas (tables 3 and 4).

DISCUSSION

Research has established a correlation between cancer incidence rates and the environmental factors latitude, temperature and water consumption. Cancer incidence rates generally increase with increasing latitude.20. In this study temperature exhibits a stronger correlation with cancer incidence rates than latitude. This finding supports the hypothesis that temperature is the factor that effects the cancer incidence rate and not latitude.

Ambient temperature determines the amount of perspiration needed to maintain proper body temperature. Therefore, ambient temperature determines the amount of water consumed. While water consumption is inversely correlated with cancer incidence rates it is unlikely that increased water consumption is responsible for lowering the cancer incidence rate. It is more probable that it is something in the water that is responsible for lowering the incidence of cancer in warmer climates.

In this study, fluoride concentration in the drinking water is inversely correlated with the cancer incidence rate. If fluoride were a chemoprotective agent it could explain why the cancer incidence rate is correlated with latitude, temperature and water consumption. The warmer the climate the more water is necessary to properly maintain body temperature through perspiration. People living in warmer temperatures would consume more water and therefore more fluoride.

Except for Hawaii none of the areas with high cancer incidence are found in the tropics (table 3). Almost all of the areas with low cancer incidence are found in the tropics (table 4). Hawaii is located at latitude 22 north and has an average high average temperature of 84 F. However, Hawaii ranks in the very high cancer incidence rate group with the white population having a combined cancer incidence rate of 693 per 100, 000 population. While Hawaii contraindicates the concept that cancer incidence rate is inversely correlated to temperature and positively correlated with latitude it supports the concept that fluoride is a chemoprotective agent. Hawaii does not have detectable levels of fluoride in the drinking water. Irrespective of how high the temperature or how much water is consumed the population of Hawaii will not consume additional fluoride because there is no fluoride in the drinking water supply. Hawaii is unique in having a very high cancer incidence rate in spite of its low latitude and high temperature. Hawaii is also unique in having no detectable fluoride in the drinking water supply.

New Mexico poses a unique comparison of drinking water fluoride concentration and the cancer incidence rate. The State of New Mexico has the distinction of being listed in both the very high cancer incidence rate group for non-Hispanic whites and also in the very low cancer incidence rate group for American Indians. With the exception of the major population centers of Albuquerque and Santa Fe many areas in the state report the fluoride concentration in the drinking water to be over 1.5 mg/l.44 Many water samples report fluoride concentrations above 5 mg/l and concentrations up to 20 mg/l have been documented.45 However, the major population centers have drinking water with low fluoride concentrations.45 The population demographics historically were made up of the white population concentrated in the cities with low fluoride in the drinking water and the American Indian population located in the rural areas with high levels of fluoride in the drinking water. The non-Hispanic white population of New Mexico has a combined male and female cancer incidence rate of 615 per 100,000 people. The American Indian population of New Mexico has a combined male and female cancer incidence rate of 299 per 100,000 individuals. The Indian population of New Mexico consumes a much larger amount of fluoride than the white population.

A factor affecting the fluoride intake of Asian populations is the fluoride found in tea.46 Even in soils with low fluoride content the tea plant has the unique ability to concentrate fluoride in its leaves. Lakdawala et al analyzed the fluoride concentration of different foods and found tea to contain higher fluoride concentrations than any other food.46 Tea leaves high in fluoride have been found to cause fluorosis when both the drinking water and the diet are low in fluoride.47

Bombay is located in a State with endemic fluorosis. However Bombay has very low cancer incidence and very low fluoride in the drinking water. With low fluoride in the drinking water and a very low cancer incidence rate Bombay tends to dispel fluoride as a chemoprotective agent. However, Lakdawala et al studied the fluoride content of the food and water consumed in Bombay and found high concentrations of fluoride in the food supply as a result of being grown in areas with high fluoride concentrations in the water.46

Many potential chemoprotective agents such a lutein, EGCG, kava and vitamin D have been studied.48,49,50,1 However, identifying chemoprotective agents have proven difficult. Population studies attempting to identify the chemoprotective properties of various agents often provide conflicting results. If fluoride has chemoprotective properties it is possibility a confounding factor in epidemiological studies.

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