Cancer incidence in areas with elevated levels of ...

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Int. J. Low Radiation, Vol. 2, Nos. 1/2, 2006

Cancer incidence in areas with elevated levels of 1 natural radiation S.M.J. Mortazavi* National Radiation Protection Department (NRPD), Iranian Nuclear Regulatory Authority (INRA), PO Box 14155-4494, Tehran, Iran and Medical Physics Department, School of Medicine, Rafsanjan University of Medical Sciences, Imam Ali Blvd. Rafsanjan, Iran Fax: +98-391-822-0097 E-mail: [email protected] *Corresponding author

M. Ghiassi-Nejad National Radiation Protection Department (NRPD), Iranian Nuclear Regulatory Authority (INRA), PO Box 14155-4494, Tehran, Iran and Biophysics Department, Tarbiat Modares University (TMU), Tehran, Iran E-mail: [email protected]

P.A. Karam Department of Environmental Medicine, University of Rochester, 601 Elmwood Ave Box HPH, Rochester, NY 14642, USA E-mail: [email protected]

T. Ikushima Biology Division, Kyoto University of Education, Kyoto 612- 8522, Kyoto, Japan E-mail: [email protected]

A. Niroomand-Rad Department of Radiation Medicine, Georgetown University, LL Bles Building, 3800 Reservoir Road NY, Washington DC 20007-2197, USA E-mail: [email protected]

Copyright © 2006 Inderscience Enterprises Ltd.

Cancer incidence in areas with elevated levels of natural radiation

J.R. Cameron

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Departments of Medical Physics, Radiology and Physics, University of Wisconsin, Madison, WI, USA Abstract: It has been reported that on reaching a certain level of cell damage the production of repair enzymes is triggered which decreases the chromosome aberrations. If this happens, prolonged exposure to high levels of natural radiation in areas with elevated levels of background radiation could decrease the frequency of chromosome aberrations. Recent epidemiological studies indicated that there is an increased risk of cancer in healthy individuals with high levels of chromosomal aberrations. Studies performed in Nordic countries as well as Italy, showed that increased levels of chromosome aberrations in lymphocytes can be used to predict cancer risk in humans. One may conclude that a dose of ionising radiation sufficient to produce a certain level of cell damage increases production of antioxidants and repair enzymes that decrease either the frequency of chromosome aberrations or the cancer risk. People in some areas of Ramsar, a city in northern Iran, receive an annual radiation dose from background radiation that is more than five times higher than the 20 mSv. Yr-1 that is permitted for radiation workers. Inhabitants of Ramsar have lived for many generations in these high background areas. If an annual radiation dose of a few hundred mSv is detrimental to health, causing genetic abnormalities or an increased risk of cancer, it should be evident in these people. The absorbed dose rate in some high background radiation areas of Ramsar is approximately 55-200 times higher than that of the average global dose rate. It has been reported that 3–8% of all cancers are caused by current levels of ionising radiation. If this estimation were true, all the inhabitants of such an area with extraordinary elevated levels of natural radiation would have died of cancer. Our cytogenetic studies show no significant differences between people in the high background area compared to people in normal background areas. As there was no increased level of chromosome aberrations, it may be predicted that the cancer incidence is not higher than in the neighbouring areas with a normal background radiation level. Although there is not yet solid epidemiological information, most local physicians in Ramsar report anecdotally that there is no increase in the incidence rates of cancer or leukemia in their area. There are no data to indicate a significant increase of cancer incidence in other high background radiation areas (HBRAs). Furthermore, several studies show a significant decrease of cancer death rates in areas with high backgrounds. It can be concluded that prolonged exposure to high levels of natural radiation possibly triggers processes such as the production of antioxidants and repair enzymes, which decreases the frequency of chromosome aberrations and the cancer incidence rate. Keywords: Ramsar; cancer; high background radiation areas; natural radiation. Reference to this paper should be made as follows: Mortazavi, S.M.J., Ghiassi-Nejad, M., Karam, P.A., Ikushima, T., Niroomand-Rad, A. and Cameron, J.R. (2006) ‘Cancer incidence in areas with elevated levels of natural radiation’, Int. J. Low Radiation, Vol. 2, Nos. 1/2, pp.20–27. Biographical notes: Dr. S. Mohammad J. Mortazavi is Vice Chancellor for Academic Affairs at the Rafsanjan University of Medical Sciences (RUMS). He is Chief Academic Officer of the university and is responsible for academic leadership. He also holds the position of Associate Professor of Medical Physics in the School of Medicine. He was also affiliated with the National Radiation Protection Department (NRPD) of the Iranian Nuclear Regulatory

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S.M.J. Mortazavi et al. Authority. He has authored many papers in the area of natural radiation, radiation hormesis, radioadaptive response and the possible role of radioadaptive response in radiation protection. In 2001, he was awarded a post-doctoral fellowship by Japan Society for the Promotion of Science (JSPS). As a post-doctoral fellow he worked on non-responsiveness and induction of synergistic effect, the two different phenomena that affect possible implications of radioadaptive response in radiation protection. P.A. Karam is currently the Radiation Safety Officer and an adjunct member of the faculty at the University of Rochester and continues work on his PhD, which he is earning through the Ohio State University’s Environmental Sciences Graduate Program. Takaji Ikushima is Professor of Biology at Kyoto University of Education, Japan. He received his basic degree in Agricultural Science from Kyoto University and a PhD in Experimental Genetics, also from Kyoto University. He spent several years as a visiting researcher at the University of California and Brookhaven National Laboratory, USA. His major interest is in radioadaptive response. Professor Azam Niroomand-Rad is Director of Clinical Physics in the Department of Radiation Medicine at Georgetown University Medical School. She obtained her PhD in atomic and molecular physics from Michigan State University, USA. She has been working as a clinical medical physicist since 1980 after completing her post-doctoral research in medical physics at the University of Wisconsin, Madison, USA. She has been certified by the US Board of Radiology (ABR) and the US Board of Medical Physics. She has published many articles and book chapters. In addition to her teaching, research and cancer patient care in the department, she has been very active in the scientific, educational and professional activities of the US Association of Physicists in Medicine(AAPM) and International Organisation for Medical Physics (IOMP). She is recognised by her peers as Fellow of AAPM and as Diplomat of the ABR. She has taught at the International Atomic Energy Agency (IAEA). She has received the Teacher of the Year Award from the Association of Residents in Radiation Oncology. She is currently serving as an associate editor of the Medical Physics Journal, Chair of the AAPM International Affairs, Chair of the AAPM International Scientific Exchange Programmes and President of the IOMP (2003–2006). Dr Cameron died before publication of this paper. John Roderick Cameron was Emeritus Professor at the University of Wisconsin-Madison in the Department of Medical Physics, Radiology and Physics and Visiting Professor at the University of Florida Department of Radiation Oncology. He completed his PhD in Nuclear Physics from University of Wisconsin-Madison in 1952 and changed to Medical Physics in 1958. He was a founding member of the AAPM and its tenth President. His research interests were in TLD, accurate bone measurement, instrumentation for QC of x-ray images, and the health effects of low levels of ionizing radiation. He co-authored several books. In 1981 he was the founding Chair of the Department of Medical Physics at UW-Madison. Since his retirement in 1986 he had sought to educate the public about radiation. He believed that moderate dose rate radiation was probably beneficial and that human research is necessary to determine the optimum dose rate. Sadly, Dr Cameron died while this paper was being prepared for publication.


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Introduction

Studies on the health effects in people exposed to elevated levels of natural radiation are unique, as compared with studies on radiation workers or residents of the areas contaminated by fallout from nuclear weapons or accidents who have been exposed to low levels of radiation only for a limited time, while the inhabitants of high background radiation areas (HBRAs) have lived in these areas for many generations (Sugahara,1997). Substantial evidence shows that there is no significant difference in cancer mortality rate of the inhabitants of high background radiation areas compared to the inhabitants of normal background radiation areas (NBRAs). On the other hand there are published reports indicating that there is a statistically significant difference in the background frequency of chromosome aberrations of the inhabitants of HBRAs compared to NBRAs. These facts raise an important open question: While there is a significant increased frequency of chromosome aberrations in the inhabitants of HBRAs, why the inhabitants show no increased cancer incidence? Ramsar, a city on the Caspian Sea in northern Iran, hosts the highest measured natural background radiation levels in the world (Figure 1). These are due to the local geology and hydrogeology and, in some places, delivered radiation doses far in excess of those recommended for radiation workers. A population of about 2000 is exposed to average annual radiation levels of 10.2 mGy/yr and the highest recorded dose rates are about 260 mGy/yr. These high radiation levels are due to the deposition of 226Ra in local rocks and, because these rocks are used in the construction of many local houses, interior radiation levels are often similar to those found outside. Figure 1

Average and Maximum annual background absorbed doses (mGy/yr) for the inhabitants of some countries and for areas with high levels of natural radiation

Source: (Used with permission of Radiation Research Foundation, Kyoto, Japan)

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Natural radiation and cancer

The absorbed dose rates in some HBRAs of Ramsar are approximately 55–200 times higher than that of normal background radiation areas (NBRAs) (Sohrabi et al., 1997). Assuming linear dose-effect relationship from high exposure levels down to

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environmental levels, 3–8% of all cancers are caused by current levels of ionising radiation (Jung and Burkart, 1997; UNSCEAR3, 1993). NRPB in the UK has reported that living for a lifetime in a house where radon is at the action level of 200 Bq/m3 carries 3-5% risk of fatal lung cancer (NRPB 2000). It should be noted that radon levels in some regions of Ramsar are up to 3700 Bq/m3 (Table 1). Table 1 Mean and maximum radon levels in different regions of Ramsar, Iran Regions Talesh Mahelleh

No. of Rooms Tested 137

Mean (Bq/m3) 615

Maximum (Bq/m3) 3700

Chaparsar

65

326

1983

Ramak

49

246

1459

Ramsar Schools and HBRAs

63

258

1572

USA, EPA Level Sweden Level

148 70

New Houses

200

Renovated Houses

400

Existing Buildings Source: (Sohrabi, 1990)

If such estimations were true, almost all of the inhabitants of such an area with extraordinary elevated levels of natural radiation would have died of cancer. Interestingly, the preliminary results of our studies on the inhabitants of these areas showed no observable detrimental effect. Our studies on the hematological parameters showed that there was no statistically significant difference between the residents of HBRAs compared to the inhabitants of NBRAs in all of studied parameters. Furthermore, the results of our preliminary immunological studies showed a slight increase in IgA and IgG levels of the residents from high background compared to normal background radiation area. However, this increase was not statistically significant. There is not yet a solid epidemiological information available for Ramsar area. However, most local physicians in Ramsar believe that there is no increase in the incidence rate of solid cancers or leukemia.

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Induction of radioadaptive response

The radioadaptive response may be defined as the induction of double-strand break repair by small doses of radiation (Ikushima and Mortazavi, 2000). Despite the fact that molecular mechanisms behind the radioadaptive response are still not known clearly, evidence indicates the existence of a faster and enhanced repair of DNA double-strand breaks in adapted cells (Ikushima, Aritomi and Morisita, 1996). Majority of the inhabitants of HBRAs of Ramsar lived there for many generations, so we performed a research to assess whether they developed a radioadaptive response to high levels of natural radiation. Our results indicated that the frequency of chromosome aberration in


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the lymphocytes of the inhabitants of HBRAs after exposure to a challenge dose of 1.5 Gy gamma rays was significantly lower than that of the inhabitants of a natural background radiation area. The results obtained in this study indicated 56% fewer chromosome aberrations in the inhabitants of HBRAs compared to residents of a neighbouring normal background radiation area (Mortazavi, Ghiassi Nejad and Beitollahi, 2001).

3.1 The role of repair enzymes It has been reported that upon reaching a certain level of cell damage the production of repair enzymes is triggered which decreases the chromosome aberrations (Pohl-Ruling et al., 1991). Pohl-Ruling and her colleagues in a study on the chromosome aberration frequency of the residents of Salzburg, Austria after Chernobyl accident, showed that in the two persons who were cytogenetically examined before the Chernobyl accident, the aberration yield increased significantly from 1984/5 to 1987. Despite the fact that there was an increase in their cumulative doses, the frequency of chromosome aberrations showed a decrease in 1988 and a further decrease in 1990. This important finding confirms the assumption that repair enzymes could be triggered by a certain amount of damage to the DNA. It can be predicted that prolonged exposure to natural radiation in areas with elevated levels of background radiation could decrease the frequency of chromosome aberrations. Our results are consistent with this assumption. On the other hand, there are reports indicating that increased levels of chromosome aberrations in lymphocytes can be used to predict cancer risk in humans (Bonassi et al., 2000). Recently, studies performed in the Nordic countries (Denmark, Finland, Norway and Sweden) and in Italy showed that chromosome aberration frequency is predictive of cancer risk. In this regard, it can be concluded that upon reaching a certain level of cell damage the production of repair enzymes is triggered which decreases the chromosome aberrations and the cancer risk.

3.2 Cancer incidence in other HBRAs The epidemiological study conducted on the residents of the high background radiation areas of Yangjiang, China performed during the period of 1987–1995 (926, 226 person-years) did not show any increased cancer risk associated with high levels of natural radiation. On the contrary, the mortality of all cancers in HBRAs was generally lower than that of the control area, however this difference was not statistically significant (Tao et al., 2000). In India, another study on the cancer incidence in the residents of HBRAs of Karunagapally taluk, where the dose rate is up to 70 mGy/yr was performed. The results obtained in this study indicated that the cancer incidence was not higher in the HBRAs compared to NBRAs (Nair et al., 1999). These recent findings confirm previous reports on the lack of any detectable increased risk in the residents of high background radiation areas (Kondo, 1993; UNSCEAR, 1994).

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Conclusions

Inhabitants of high background radiation areas have lived in these areas for many generations. In this regard, studies on the inhabitants of these areas are unique, as in epidemiological studies on the health effects of low level radiation of all the other under-study groups such as radiation workers have been exposed to low levels of radiation only for a limited time. The absorbed dose rate in some high background radiation areas of Ramsar is approximately 55-200 times higher than that of normal background radiation areas. It has been reported that current levels of ionising radiation cause 3–8% of all cancers. If this estimation were true, all the inhabitants of such an area with extraordinary elevated levels of natural radiation would have died of cancer. Based on the results of our cytogenetical studies, it can be predicted that there is no increased risk of cancer in the inhabitants of the high background radiation areas of Ramsar. Epidemological studies on the cancer risk in residents of Yangjiang, China and Kerala, India – two other well-known areas with high levels of ionising radiation – could not show any increased risk of cancer in the inhabitants of high background compared to residents of control areas. It can be concluded that current estimations regarding increased cancer risk following exposure to low level or natural radiation are not valid. Currently, a fear has been created in the minds of the inhabitants of some high background radiation areas around the world. The media, regulatory authorities and scientists should inform the people that there is no such report about the existence of detectable detrimental effects in the inhabitants of high background radiation areas. Furthermore, as our results showed the induction of radioadaptive response in the inhabitants of high background radiation areas, it can be claimed that the lack of harmful effects is possibly due to the enhanced effectiveness of the repair capacity of the living cells of the inhabitants of these areas.

Acknowledgements The authors express their deep appreciation to Professor Z. Jaworowski, the past Chairman of UNSCEAR for his critical review of the manuscript.

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Kondo, S. (1993) Health Effects of Low Level Radiation, Kinki University Press, Osaka. Mortazavi, S.M.J., Ghiassi Nejad, M. and Beitollahi, M. (2001) ‘Very high background radiation areas (VHBRAs) of Ramsar: do we need any regulations to protect the inhabitants?’, Proceedings of the 34th Midyear Meeting Radiation Safety and ALARA Considerations for the 21st Century, California, USA, pp.177–182. Nair, M.K., Nambi, K.S., Amma, N.S., Gangadharan, P., Jayalekshmi, P., Jayadevan, S., Cherian, V. and Reghuram, K.N. (1999) ‘Population study in the high natural background radiation area in Kerala’, Radiat Res., India, Vol. 152, No. 6, pp.$145–$148. NRPB (2000) ‘Health risks for radon’, Environmental Radon Newsletter, No. 25. Pohl-Ruling, J., Haas, O., Brogger, A., Obe, G., Lettner, H., Daschil, F., Atzmuller, C., Lloyd, D., Kubiak, R. and Natarajan, AT. (1991) ‘The effect on lymphocyte chromosomes of additional radiation burden due to fallout in Salzburg (Austria) from the Chernobyl accident’, Mutat Res., Vol. 262, No. 3, pp.209–217. Sohrabi, M. (1990) ‘Natural radioactivity of the soil samples’, Proceedings of an International Conference on High Levels of Natural Radiation, Ramsar, Iran. Sohrabi, M., Bolourchi, M., Beitollahi, M. and Amidi, J. (1997) ‘Natural radioactivity of the soil samples’, In Wei, L., Sugahara, T. and Tao, Z. (Eds.): Proceedings of the 4th International Conference on High Levels of Natural Radiation, Amsterdam, Elsevier, pp.129–132. Sugahara, T. (1997) ‘The radiation paradigm regarding health risk from exposure to low dose radiation’, In Wei, L., Sugahara, T. and Tao, Z. (Eds.): Proceedings of the 4th International Conference on High Levels of Natural Radiation, Amsterdam, Elsevier, pp.167–178. Tao, Z., Zha, Y., Akiba, S., Sun, Q., Zou, J., Li, J., Liu, Y., Kato, H., Sugahara, T. and Wei, L. (2000) ‘Cancer mortality in the high background radiation areas of Yangjiang, China during the period between 1979 and 1995’, Journal of Radiation Research, Tokyo, Vol. 41, pp.31–41. United Nations Scientific Committee on the Effects of atomic Radiation (1993) Sources and Effects of Ionizing Radiation. UNSCEAR (1994) ‘Sources and effects of ionizing radiation’, United Nations Scientific Committee on the Effects of Atomic Radiation, New York.

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This paper was presented at the 2nd International Conference on ‘The Effects of Low and very Low Doses of Ionising Radiation on Human Health’, 2001, June 27-29 Dublin Institute of Technology, Radiation and Environmental Science Centre, Ireland. Since deceased. United Nations Scientific Committee on the Effects of Atomic Radiation, 1993.