The Fluoride-Cancer Connection: History and Current Science

Transcription

1 The Fluoride-Cancer Connection: History and Current Science Chris Neurath Fluoride Action Network Bone cancer, rates by age group SEER data Adjusted rate (per 100,000) Male Female Age class (5 year groupings)

2 Cancer incidence has been slowly rising in the US over time Incidence rate of all cancers combined, time-trends SEER 700 Rate, age adjusted (per 100,000) Male Female Year

3 Cancer rates are highly age-dependent, as much as doubling for every 10 years older All cancers combined, rates by age group SEER data Adjusted rate (per 100,000) Male Female Age class (5 year groupings)

4 Childhood bone cancers are even more age-dependent, as much as tripling between 5 year age classes. Two peaks, at age 15 and around age 80+. Bone cancer, rates by age group SEER data Adjusted rate (per 100,000) Male Female Age class (5 year groupings)

5 Osteosarcoma incidence is highly age-dependent. Suggests cause might also be age-dependent. Age distribution of osteosarcoma (SEER data ) Number of cases Male Female Age

6 Types of Cancer Studies I. Molecular or Cell Level Studies II. Controlled Animal Experiments III. Human Population (Epidemiology) Studies 1. All group-level A. Group-level ecologic data 2. Some individuallevel B. Individuallevel data 3. Case-control 4. Cohort

7 Example of ecologic data from SEER online mapping of cancer data

8 Another example of an ecological study, comparing population fluorosis rates with osteosarcoma rates per 10 million Provinces shaded by incidence rates for dental fluorosis and osteosarcoma

9 National average = 1.7 per million per year for both sexes, all ages

10 Ecologic grouped data versus individual data: Which is better? Group data can suffer from inaccuracies. For example: if a county is designated fluoridated when 65% of residents have F water, the remaining 35% of that population is incorrectly classified as exposed. Such misclassification reduces the ability of a study to detect an effect. Group data can not be easily corrected for confounding effects. For example, if radium in water is another risk factor, and you only know the average level of radium in a county, there will be errors when applying this average to everyone because some people in the county will actually have high radium and some will have low radium. Group data is usually much easier to obtain. Studies can be quick and inexpensive, compared to interviewing or obtaining specimens from individuals. Group data studies are usually considered exploratory rather than providing strong evidence.

11 Yiamouyiannis & Burk 1977 The graph that started it all Overall cancer death rates continued climbing in fluoridated cities after fluoridation but started leveling off in neverfluoridated cities.

12 Time line history of fluoride-cancer studies 1950 Taylor 1975 Yiamouyiannis reaction to Yiamouyiannis > 1976 Hoover 1980 NTP begin --> 1991 NTP end 1984 Lynch reaction to NTP > 1991 Hoover 1992 Cohn 1992 Douglass & Hoover begin ---> 1995 Gelberg 2001, 2006 Bassin 2006? Douglass & Hoover end?

13 Cast of Characters Robert Hoover National Cancer Institute Chester Douglass Harvard Dental School Gary Whitford Medical College of Georgia John Yiamouyiannis National Health Federation Charles Lynch Iowa Cancer Registry

14 Condensed History of Cancer-Fluoride Studies Year Researcher Type of Study 1950 Taylor animal experiment 1975 Yiamouyiannis mortality, major cities, ecologic 1970s- reactions to Yiamouyiannis mortality, ecologic 1980 NTP animal experiments begun animal experiments 1984 Lynch incidence, Iowa, ecologic 1991 NTP completed animal experiments 1990s- reactions to NTP 1991 Hoover incidence, ecologic 1992 Cohn incidence, NJ, semi-ecologic 1992 Douglass & Hoover begun case-control, hospital patients 1995 Gelberg case-control, New York State 2001, 2006 Bassin case-control, hospital patients 2006? Douglass & Hoover 14 years and still not published

15 Summary of Positive Results: Fluoride-Cancer Epidemiology Studies Increased Risk Factor all cancers, mortality bladder cancer, males osteosarcoma, young males osteosarcoma, young males osteosarcoma, young females osteosarcoma, young males osteosarcoma, young males osteosarcoma, unknown 1977 Yiamouyiannis 1984 Lynch 1991 Hoover 1992 Cohn 1995 Gelberg 1995 Gelberg 2006 Bassin 2006? Douglass & Hoover

16 From Bassin Odds Ratios for age-specific fluoride exposure in males; based on model with covariates. Error bars show confidence intervals. When above 1.0 is statistically significant.

17 Bassin 2001, 2006 Strengths of her study: first and only age-specific exposure analysis focus on at-risk age group <20 year olds accurate determination of drinking water fluoride controlled for: - age, sex, geographic area, socioeconomic status, use of fluoride dental products relatively large sample size no errors or omissions in analyses

18 Cover-up of Bassin s groundbreaking study which found strong link between fluoride and osteosarcoma? 2001 Bassin s study complete and awarded PhD. No public announcement or attempt to publish results Douglass, her advisor, states his team has found no evidence of a link Douglass reports directly to NRC that his team has found no link, even though he gives citation to Bassin thesis On tip, FAN and EWG discover Bassin thesis. Only available copy is kept in Harvard Medical School Rare Books Room FAN makes public; EWG requests formal investigation of Douglass for cover-up Bassin publishes study Douglass criticizes publication of Bassin study, claiming his follow-up studies will be superior, but gives misleading statements and few details. [Fox25 TV Boston investigative story]

19 NRC 2006 Review Chapter on fluoride and cancer Much better and more comprehensive review of science than ever done before. Accurately describes the strengths and weaknesses of most studies. Conclusion and recommendations for further research are weak.

20 NRC conclusions on carcinogenicity NRC 2006: Fluoride appears to have the potential to initiate or promote cancers, particularly of the bone, but the evidence to date is tentative and mixed. Improvement over previous NRC report: NRC 1993: the available laboratory data are insufficient to demonstrate a carcinogenic effect of fluoride in animals. The subcommittee also concludes that the weight of the evidence from more than 50 epidemiological studies does not support the hypothesis of an association between fluoride exposure and increased cancer risk in humans. [Note that the 1993 NRC committee only evaluated 7 human studies, not 50 as implied.]

21 NRC comments on Bassin 2001 Potential for selection bias because controls were hospital orthopedic patients. Many of these might have been bone fracture patients and fluoride might effect risk for bone fractures. Other NRC comments were all addressed in Bassin s 2006 published version.

22 Controls? Cases

23 A single study in China found fluoride protected against fractures at 1 ppm; but only studied adults. Bone Fracture Risk versus Fluoride Exposure (for ages > 20, China) Relative risk of fracture Fluoride exposure (ppm in water)

24 Sensitivity Analysis Does low fluoride cause more broken bones? Bone Fracture Risk versus Fluoride Exposure (for ages > 20, China) 1.6 Relative risk of fracture Fluoride exposure (ppm in water) AND Did enough controls have broken bones? to explain away Bassin s findings by selection bias?

25 Probably Not Even if low fluoride does cause broken bones, sensitivity analysis shows: More than 75% of the controls would have to have broken bones. AND The increased risk of broken bones for low fluoride consumers would have to be 5-fold. Douglass reported most controls were trauma patients, and there is no existing study showing significant increased risk of broken bones in children exposed to low fluoride.

26 Douglass & Hoover ? Major questions surrounding study: 14 years and still no formal publications. No age-specific exposure analyses attempted to date. Bone fluoride measures lifetime cumulative exposure. Can not be used for age-specific analysis. Bone fluoride specimens from controls who have bonecancer! [from FOIA and NRC documents] Preliminary reported results have never included adequate information on age ranges, sex specific, statistical significance, or control for confounding factors.

27 NRC comments on Gelberg 1995 Although Gelberg concluded there was no effect, the NRC were not so sure. They focused on the analyses they felt were most reliable and found there was evidence of an increased risk from fluoridated water. They considered Gelberg s study the strongest published study up until Bassin.

28 Non-linear dose-response, but positive risk for all exposures. Gelberg 1995: Risk versus cumulative exposure from drinking water 12 Relative risk of osteosarcoma (Odds Ratio) Fluoride Exposure (lifetime mg ingested) Females Males

29 NRC said non-linear dose-response can still be evidence of association, but of a more complex relationship between exposure and risk 6 Linear and non-linear dose-response curves Response (risk ratio) linear non-linear Exposure

30 Conclusions: Several studies have shown evidence that fluoride causes osteosarcoma and possibly other cancers Bassin s is the strongest to date Douglass s follow-up studies will need to correct serious deficiencies if they are to supersede Bassin work Re-examination of earlier studies (like Gelberg s) and initiation of new studies is warranted, especially taking into account Bassin s finding of an age-specific effect Unlike other possible environmental carcinogens, fluoride is purposely added to water for dental purposes: In a 1998 interview the late Dr. John Colqhuoun asked: How many teeth would you have to save to justify one child dying from osteosarcoma?