In spite of conflicting results, some studies show that individuals residing in High Background Radiation Areas (HBRAs) of Ramsar have an increased frequency of detectable abnormalities in unstable chromosome aberrations. We have previously reported that in Ramsar, the maximum credible annual radiation exposures is up to 260 mGy. If an annual radiation exposure of a few hundred mSv is detrimental to health, causes genetic abnormalities, or an increased risk of cancer, it should be evident in these people. Although there is not yet solid epidemiological information, most local physicians in Ramsar report anecdotally there is no increase in the incidence rates of cancer in their area. On the other hand, we have previously shown that in Ramsar, the highest lung cancer mortality rate was in Galesh Mahaleh, where the radon levels were normal. However, the lowest lung cancer mortality rate was in Ramak, where the highest concentrations of radon in the dwellings were found.
http://www.sums.ac.ir/~mmortazavi/ramsar.html
Dear Dr. Mortazavi, as we had the opportunity to discuss earlier, this is indeed the greatest paradox regarding HBRAs: as far as I recall,, similar higher than normal frequencies of chromosomal abnormalities had been found in other areas such as in Kerala, ,India, despite the lack of a recognized increase in cancer occurrence. Many caveats indeed exist: like you also pointed out, most of these reports are rather ecological than epidemiological and there are problems in keeping good cancer registry records. However, the equation according to which higher aberration frequency equals increased risk of cancer occurrence, which was proved by several European studies (see Bonassi et al, Carcinogesis, 2008 "Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries.") seems not to hold for HBRAs. What can we say? is there a proof of in vivo adaptive response, as you also have indeed advocated? I guess better qualified colleagues of ours may have brighter answers!
Dear Professsor Mortazavi.
As you know, radiation carcinogenesis is a complex process that has 3 phases of initiation, promotion and progression. Also, cancer is a genetic and epigenetic based phenomenon that during which many factors can effect it. In related to HNBRAs and their inhibitants, the biological findings have ignored the role of epigenetics in radiation assissted phenomena such as radiation carcinogenesis and radiation adaptive response. Also, the last experimental studies for biological assessment of radiation carcinogenesis have 3 following deficiencies:
1) The studies that deny the role of immune system after radiation exposure
2) The role of more DNA repair activation because of epigenetic alterations
3) The role of good signals that relaesed during or after radiation exposure
Dear Dr. Mortazavi,
I would like to also highlight the complexity of carcinogenesis. Intracellular damages contribute only to some events of the complex process, and we should not neglect the following steps. For example, some researchers argue that radon progeny increases cancer risk mainly because alpha-particles kill cells providing place for clonal growth of already mutated cells (Heidenreich & Paretzke, 2008). UV-radiation may have a similar effect (Chao et al., 2008 and references therein). In addition, ionizing radiation may also affect tumour progression. Although frequency of chromosome abberations may have some indications for cancer risk (e.g. it may show the DNA-repair deficiency of the individual), these quantities are basically different. Chromosome abberation is an effect on the individual cells (or on a cluster of interacting cells), while cancer is a disease of the complex organism. In one of our earlier works (Madas & Balásházy, 2011), we also highlighted that effects at the tissue level may be more important even in radiation mutagenesis than cellular effects (at least in some exposure scenarios).
Regarding the cancer mortality in HBRA regions, my first question is about the life expectancy of the population. If people die in relatively young ages because of any reasons, they simply do not have enough time to get cancer. If they have a similar age distribution as the control group then the reason can be adaptation. However, this is rather the adaptation of the population than that of the individual. Therefore, I would not call it radioadaptive response. To test the hypothesis of the adaptation of the population, emmigrated and immigrated people could be studied if they have a significant number.
Best regards,
Balázs
Chao, D. L., J. T. Eck, D. E. Brash, C. C. Maley, E. G. Luebeck. „Preneoplastic lesion growth driven by the death of adjacent normal stem cells”. Proc Natl Acad Sci USA 105 (2008): 15034–15039.
Heidenreich, W. E., H. G. Paretzke. „Promotion of initiated cells by radiation-induced cell inactivation”. Radiat Res 170 (2008): 613–617.
Madas, B. G., I. Balásházy. „Mutation induction by inhaled radon progeny modeled at the tissue level”. Radiat Environ Biophys 50 (2011): 553–570.
Dear Dr. Madas Thank you for your response. Currently, there is no evidence to support this claim that the life span of HBRA residents is different than that in residents of nearby NBRAs. Regarding your suggestion for checking immigrants, please note that the very limited number of immigrants cannot provide us required statistical power. In this light, we are working on tumor markers in HBRA residents.
It has also to be added, in support of dr. Mortazavi's viewpoint, that in many cases the populations residing in HBRAs have done so for centuries, i.e. they have had limited influx of people from other regions. And, if it is true that they may have a shorter life-span compared to that recorder in Europe, Japan, the US and so on, I guess the comparison for life expectancy or cancer incidence and/or mortality has been done with populations of the same Country but living in different regions. Having said that, it is certainly true that carcinogenesis is a complex process...
Chromosome rearrangements via translocations and inversions leading to production of chimeric oncoprotein proteins (oncogene fusion, e.g., via interchromosomal translocation) and oncogene overexpression (e.g., via intrachromosomal amplification), may be directly associated with cancer risk, but I am not sure about other chromosome aberrations in terms of a direct association with cancer risk.
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