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No Increased Risk of Cancer after Long-term Low-dose-rate Radiation Exposure in Taiwan.

In the Journal's winter issue, Bobby Scott discussed natural cancer-facilitating oxidative damage and barriers to cancer and their enhancement by low radiation doses, leading to a reduction in natural cancer. (1) Evidence of this radiobiology was studied in the "serendipitous experiment" that started 35 years ago with the inadvertent exposure of those who occupied more than 180 buildings in Taiwan that were constructed using steel contaminated with radioactive cobalt-60. (2) These buildings were constructed in the early to mid-1980s and occupied, starting in 1983, by more than 8,000 people over differing time intervals. It was not until mid-1992 that the people who resided or studied in these buildings began to be identified and informed about this hazard. (2,3) In 1996, residents began to be evacuated from apartments with high radiation levels; half of them were moved as of 2003. (3)

The early analysis by Chen et al. published in this journal in 2004 (3) suggested a remarkable decrease in cancer rates in the exposed population. However, a recent article by Hsieh et al. (4) states that risks of leukemia, breast cancers, and all cancers were significantly increased for occupants of the contaminated buildings. The Hsieh et al. study is an update of the cancer risks that were reported by Hwang et al. in 2006 (5) and updated in 2008. (6)

In a letter to the editor, Mohan Doss (7) states that Hsieh et al. used Cox proportional risk models to determine the hazard ratios for cancer incidence and claim that dose-dependent risks were statistically significant. These conclusions are similar to those of the 2008 update by Hwang et al. However, the 2006 article by Hwang et al. showed (in Table III) that 95 "all cancers" cases were observed up to the end of 2002, while 114.9 were expected. This is a significant reduction of all cancers following years of exposure to low-dose radiation. Doss pointed out that Hsieh et al. failed to discuss the significant reduction in total cancers in the irradiated cohort. Doss also recommended that additional data with better statistics be obtained before concluding that there is increased risk for specific cancer types. Use of proportional hazard models for estimating hazard ratios is not justified because the results from such analysis can mask the observation of a reduction of all cancers. (7)

It is not appropriate to simply link a low dose of ionizing radiation, using a mathematical model, to an increased risk of cancer. Because of the high natural incidence of cancers and the many factors that affect cancer risk, it is impossible to establish a statistical relationship between low doses or low levels of radiation and an elevated risk of cancer. It is well known that a high dose or a high dose rate is harmful. Such exposures inhibit or damage the adaptive protection systems and shorten longevity. They may also increase the risk of cancer. However, there is evidence that low doses or a low dose rate of radiation stimulates the protection systems, and this can reduce both radiogenic and non-radiogenic cancer incidence. (8,9)

For the long-term exposures experienced in Taiwan, "cumulative dose" is not a useful statistic. The adaptive protection systems produce more antioxidants to neutralize the radiation-induced reactive oxygen species (ROS) that damage biomolecules, including DNA. The systems that repair the damage caused by ROS and direct radiation "hits" are up-regulated. The systems that remove unrepaired cells are also stimulated, as is the immune system for enhanced destruction of cancer cells, resulting in a lower risk of cancer. (9)

Dose rate is the proper variable for assessing the Taiwan exposures, and longevity (not cancer) is the more appropriate measure of the health effect. Studies on animals and humans generally reveal that there is an increase of lifespan when the ambient dose rate is above the normal background level, but not higher than the threshold for the onset of harmful effects. (9)

The 2004 study by Chen et al. determined, very roughly, the radiation exposures received by the occupants, and calculated the expected cancer mortality using the linear no-threshold (LNT) model. (3) For three cohorts (high, medium and low), it evaluated the mean annual dose in the first year (1983), the 20-year cumulative dose, and the 20-year "collective dose." In 1983, the 1,100 people in the high cohort received doses whose average was about 525 mSv; their 20-year doses averaged 4,000 mSv. In 1983, the 900 people in the medium cohort received doses whose average was about 60 mSv; their 20-year doses averaged 420 mSv. (3) [The equivalent dose, sieverts (Sv), equals absorbed dose, gray (Gy), for gamma radiation. 1 gray equals 1 joule/kg.]

Chen et al. estimated the collective dose of the exposed population to be 4,000 person-Sv, and calculated the expected number of radiogenic excess leukemia and cancer deaths to be about 70, from 1983 to 2002. However, only two leukemia and five cancer deaths were reported during this period among the occupants. Chen et al. could not obtain their registration data and could not correct for the risk factors, such as age at initial exposure. The calculated number of non-radiogenic cancer deaths was 232, assuming the demographics of the occupants to be the same as the population of Taiwan. (3) In fact, the average age of the occupants was younger than that of the comparison population.

The 2006 study by Hwang et al. (5) had the proper registration data for 7,271 subjects and much more accurate information about their individual radiation exposures. Cancer risks were determined and compared with those populations with the same temporal and geographic characteristics in Taiwan by standardized incidence ratios (SIR), adjusted for age and gender. The association of cancer risks with excess cumulative exposure was further evaluated for their relative risks by the Poisson multiple regression analysis. As shown in the first line of Table III in Hwang et al. (2006), for the period 1983-2002, the total number of observed cancers was 95; the expected number was 114.9, and the SIR for all cancers was 0.83 (95% CI: 0.66-0.99). This indicated a significant reduction of "all cancers" after low-dose irradiation.

As mentioned above, dose rate is the proper variable, and longevity is the most appropriate measure of radiogenic health effects. The analysis by Cuttler et al. of a study on groups of dogs exposed to different dose rates of cobalt-60 irradiation revealed a threshold dose rate for the onset of reduced lifespan of 700 mGy per year (see Figure 1 below). (9) Assuming that dogs model humans, a lifespan increase of up to about 15 percent could be expected for a dose rate between the normal background level and the 700 mGy per year threshold for harmful effects. The average 1983 exposure in the high-dose Taiwan cohort was 535 mSv (the equivalent of 525 mGy for gamma radiation), as calculated by Chen et al. (3)

The proper comparison of dose rate vs. longevity has not been reported for the Taiwan experience.

(1.) Scott BR. Small Radiation doses enhance natural barriers to cancer. J Am Phys Surg 2017;22:105-110.

(2.) Chang WP, Chan C-C, Wang J-D. 60Co contamination in recycled steel resulting in elevated civilian radiation doses: causes and challenges. Health Phys 1999;73:465-472.

(3.) Chen WL, Luan YC, Shieh MC, et al. Is chronic radiation an effective prophylaxis against cancer? J Am Phys Surg 2004;9:6-10. Available at: Accessed Feb 23, 2018.

(4.) Hsieh WH, Lin IF, Ho JC, Chang PW. 30 years follow-up and increased risks of breast cancer and leukaemia after long-term low-dose-rate radiation exposure. Br J Cancer 2017;117:1883-1887.

(5.) Hwang SL, Guo HR, Hsieh WA, et al. Cancer risks in a population with prolonged low dose-rate gamma-radiation exposure in radiocontaminated buildings, 1983-2002. Int J Radiat Biol 2006;82:849-858.

(6.) Hwang SL, Hwang JS, Yang YT, et al. Estimates of relative risks for cancers in a population after prolonged low-dose-rate radiation exposure: a follow-up assessment from 1983 to 2005. Radiation Res 2008;170:143-148.

(7.) Doss M. Comment on "30 years follow-up and increased risks of breast cancer and leukaemia after long-term low-dose-rate radiation exposure" [published online ahead of print Feb 13, 2018]. Br J Cancer doi: 10.1038/bjc.2017.481. Available at: Accessed Mar 20, 2018.

(8.) Doss M. Changing the paradigm of cancer screening, prevention, and treatment. Dose-Response 2016; 4:4:1-10. Available at: Accessed Feb 23, 2018.

(9.) Cuttler JM, Feinendegen LE, Socol Y. Evidence that lifelong low dose rates of ionizing radiation increase lifespan in long- and short-lived dogs. Dose-Response 2017;15(1):1-6. Available at: Accessed Feb 23, 2018.

Jerry M. Cuttler, D.Sc.

Ontario, Canada
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Title Annotation:Correspondence
Author:Cuttler, Jerry M.
Publication:Journal of American Physicians and Surgeons
Article Type:Letter to the editor
Geographic Code:9TAIW
Date:Mar 22, 2018
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