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Radetić, M., Kovačić, M., Parazajder, D., Radetić, Ma., Špoler Čanić, K.*

3rd International Course Multidisciplinary Approach on Thyroid Gland and Oral Cavity Carcinoma Zagreb – Croatia, September, 1st - 3rd, 2005 THE INCREASING INCIDENCE OF THYROID CANCER IN CROATIA COINCIDING WITH CHERNOBYL NUCLEAR CATASTROPHE. Radetić, M., Kovačić, M., Parazajder, D., Radetić, Ma.,

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Radetić, M., Kovačić, M., Parazajder, D., Radetić, Ma., Špoler Čanić, K.*

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  1. 3rd International CourseMultidisciplinary Approach on Thyroid Gland and Oral Cavity CarcinomaZagreb – Croatia, September, 1st - 3rd, 2005THE INCREASING INCIDENCE OFTHYROID CANCER IN CROATIA COINCIDING WITH CHERNOBYL NUCLEAR CATASTROPHE Radetić, M., Kovačić, M., Parazajder, D., Radetić, Ma., Špoler Čanić, K.* OTOLARYNGOLOGY & HEAD AND NECK SURGERY DEPARTMENT, GENERAL HOSPITAL “SVETI DUH”, ZAGREB, CROATIA *THE STATE HYDROMETEOROLOGICAL INSTITUTE OF REPUBLIC OF CROATIA, ZAGREB, CROATIA

  2. During the accident atChernobyl nuclear powerplant, on April 26th 1986,about 100 MCi of short-livedradioiodines (I-132,133,135) and 40MCi of I-131were released intothe atmosphere

  3. The main zones of soil contaminations were to the west, northwest and northeast of Chernobyl • However, after May 1st , substantial increase of the emission was reported, with the maximum on May 5th 1986

  4. Since April 30th, during heavy rainfall in south central Europe, a radioactive material was transported into Croatia - mostly to northwestern part

  5. Accumulated I-131deposition in KBq/m², as calculated by the MESUS model, for the period April 26th - May 6th 1986, for European countries (excluding former USSR): • Poland 110 • Austria 20 - 150 • Italy 5 - 100 • Bavaria 130 • ex Czechoslovakia 50 • Croatia 100 • W. Europe 0 - 20

  6. Estimated accumulation in thyroid of children and adolescents was 0,05 – 200 mSv, meaning up to 20 cGy • The risk of cancer increases progressively from 10 cGy up to 1500 cGy; larger doses are cellulicidal, so the risk of getting cancer is lower

  7. After latent period, of about 3 years after exposal, the first childhood “Chernobyl” papillary cancers of thyroid gland(ChPTCs) appeared

  8. CHARACTERISTICS OF ChPTC • Frequently associated with autoimmune thyroiditis • Solid/follicular subtype of ChPTC • Extrathyroid spreading • Common regional and distant metastases • Rearrangement of the RET oncogene - RET PTC 1(lower doses), RET PTC 3 (higher doses)

  9. The rationale of our research is to evaluate the Chernobyl catastrophe as a causative factor of accelerated increase of the thyroid cancer and to anticipate the possible further increase of incidence in the next years

  10. In Ukraine and Belarus, in 50 years following the Chernobyl catastrophe, up to 50.000 people are expected to develop thyroid cancer • The incidence rate for children’s PTC in Chernobyl area raised of factor 100 – from 0,1 to 10

  11. Our research is aimed in three directions: • Comparison of the PTC prior and after latent period of Chernobyl, regarding autoimmune thyroiditis, adenomas and nodules coinciding tumors • Epidemiological tracing target cohorts of patients born 1966 – 1986 • Attempt to find rearrangements of thyrosine-kinase domains of the RET genes, in group of 50 patients with PTC

  12. A) HistologyWe compared 3 groups of patients operated during following periods: • I 1985 – 1987 100 PTC (prechernobyl and latent period) • II 1995 – 2000 202 PTC (early postchernobyl manifest period) • III 2001 – 2004 233 PTC (later postchernobyl manifest period)

  13. All slides were rewieved by the group of our pathologists Papillary thyroid cancer inside adenoma Lymphocytic thyroiditis around papillary thyroid cancer • The results are presented in the following table:

  14. COMPARISON OF PTC ACCORDING TO HISTOLOGICAL FINDINGS IN THE REMAINING PARENCHYMA

  15. In group of non-affected by radioiodine (I) 85% of parenchyma around tumor was normal, opposite to only 48,5% in earlier radioiodine affected group (II), and 42,5% in the latter group (III) • The differences between group I vs II + III are statistically significant(p<0,01) • In group I autoimmune thyroiditis was found in only 11% of thyroids, comparing with 31,7% and 35,2%, in groups II and III respectively • In group I benign adenomas were found in only 3%,comparing with 11,9% and 8,2%, in groups II and III respectively • Both differences are statistically significant

  16. None of thyroids in group I was accompanied by autoimmune thyroiditis and/or adenomas and/or adenomas + nodules, as it was the case in group III Conclusions: These data suggest that Chernobyl catastrophe could be one of the causes of increasing incidence of PTC in Croatia

  17. B) Epidemiology In epidemiological part of our study we compared: • 1. Incidence rate of thyroid cancer vs all tumor sites since 1968 to 2002 • 2. Incidence rate in cohorts born 1966 - 1986 vs all the others • 3. Prevalence of thyroid cancer according accumulated deposition of I-131 (in KBq/m²) in all the counties of Croatia

  18. Incidence rate of malignant tumors in Croatia 1968 – 2002 (all sites) Incidence rate I N C I D E N C E TOTAL MALES FEMALES YEARS The incidence rate for all sites has been doubled since 1968 to 2002 including

  19. Incidence rate of thyroid cancer in Croatia(1968 – 2002) F:11,8 I N C I D E N C E T:7,5 TOTAL MALES FEMALES M:2,8 F:2,7 T:1,7 M:0,7 YEARS The incidence rate of TC since 1968 to 2002 raised for females 4,3 times , for males 4 times and in total 4,4 times

  20. COMPARISON CANCER REGISTRY DATA BETWEEN CROATIA AND ENGLAND In the period 1975 - 2002 the incidence rate in Croatia raised 3,9 times, and in England only 1,5 times Moreover, English curve shows only slight raising of incidence rate, while Croatian curve shows unexpectedly accelerated raising of incidence rate in mid 1990s. F 11,8 F 3,3 T 1,9 M 0,5 F 3,5x T 3,9x M 5,6x T 7,5 M 2,8 Croatia England F 1,8 T 1,4 M 0,8 F 3,1 T 2,2 M 1,2 F 1,7x T 1,5x M 1,5x

  21. INCREASING PREVALENCE OF THYROID CANCER AMONG ALL TUMOR SITES IN CROATIA Total 1968 = 0,8%  2002 = 1,7% Males 1968 = 0,3%  2002 = 0,6% Females 1968 = 1,3%  2002 = 3,1% % TOTAL MALES FEMALES YEARS

  22. INCIDENCE RATE OF THYROID CANCERCOHORTS OF BORN 1966 - 1986 BEFORE AND AFTER CHERNOBYL latencymanifestation 1966 1986 1993 2002 5 years 35 years

  23. COMPARISON OF INCREASING INCIDENCE RATE OF THYROID CANCER - COHORTS 5 - 35 vs >35 yrs TOTAL <35 >35 I N C I D E N C E YEARS 1970  2002 >35 ~2x 5 – 35 ~6x

  24. COMPARISON OF INCREASING INCIDENCE RATE OF THYROID CANCER - COHORTS 5 - 35 vs >35 yrs FEMALES Porast incidencije 5-35 i >35, žene <35 >35 I N C I D E N C E YEARS 1970  2002 >35 ~2x 5 - 35 ~9x

  25. COMPARISON OF INCREASING INCIDENCE RATE OF THYROID CANCER - COHORTS 5 - 35 vs >35 yrs MALES Porast incidencije 5-35 i >35, muškarci <35 >35 I N C I D E N C E YEARS 1970  2002 >35 ~2x 5 - 35 ~6x

  26. INCREASING PREVALENCE OF COHORTS <35 yrs vs ALL THE OTHERS 25% FEMALES TOTAL % 15% YEARS

  27. Conclusions: • Increased incidence of thyroid cancer in Croatia in late 1990s • Increased prevalence of thyroid cancer in Croatia among all the other tumor sites • Increased incidence/prevalence in Croatia in cohorts born 1966 -1986 vs elders

  28. According to meteorologic situation over Croatia, the highest deposition of radioiodine was in the period since April 29th to May 4th 1986 • Therefore, we elaborated detailed maps of radioiodine distribution, in all the counties of Croatia, in that period

  29. Total wet deposition (Bq/m²) April 29th – May 4th, 1986

  30. COMPARISON OF NEW CASES: TUMORS ALL SITES vs THYROID CANCERS IN THE COUNTIES ACCORDING TO COHORTS BORN 1966 -1986 (A) AND COHORTS BORN <1966 AND >1986 (B) COUNTY ALL SITES THYROID total increase increase increase of thyroid tumors >7% <7% no increase decrease

  31. Increasing incidence rate of all sites period ’88-’95 vs period ’96-’02 cohorts 1966-86 significant increase slight increase no increase decrease COUNTIES Without significant increase in both observed periods

  32. Increasing incidence rate of thyroid cancer period ’88-’95 vs period ’96-’02 cohorts 1966-86 significant increase slight increase no increase decrease COUNTIES In northern and western counties slight to significant increase

  33. Conclusions: • These data suggest positive correlation between the accumulated deposition of radioiodine and the incidence rate of thyroid cancer • There is no correlation between the accumulated deposition of radioiodine and the incidence rate of all the other tumor sites Geiger - Müller counter

  34. C) Molecular biological analysis • Molecular biological analyzes are “in tractu”, so no conclusions, considering genetic alterations, can be referred today

  35. As far as European population is concerned, the first results for 22 European countries are underestimated of factor 4, for the incidence of fatal and non-fatal thyroid cancer, caused by Chernobyl catastrophe “Thyroid dosimetry in Europe following the Chernobyl accident “ Brit. Journal of Rad. 73 (870): 636-40, 2000 Jun • The same results were referred from: • Debrecen(Lukacs et al),1997 • Western Poland(Niedziela et al),2003 • Cancer Registry of Czech Republic(Murbeth et al), 2004

  36. CONCLUSIONS: Histological and epidemiological data, together with clinical observations and data from mid-eastern European countries, suggest that increase of thyroid cancer, particularly in population born 1966 - 1986, is caused, at least partly, by Chernobyl catastrophe

  37. Have a nice time in Zagreb!

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