Prevalence of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Its Malignant Progression in Radiation-Exposed Population.
Authors: Iwanaga Masako , Tagawa Masuko , Tsukasaki Kunihiro , Kamihira Shimeru , Tomonaga Masao 
Published: April 2020

Abstract
The prevalence of Monoclonal Gammopathy of Undetermined Significance (MGUS) in Japanese population and that in radiation-exposed population have not been accurately determined. We performed a M-protein screening to determine the prevalence of MGUS and a cohort study to determine the probability of progression from MGUS to multiple myeloma (MM) in a large Japanese population exposed to radiation. In this study, if we could find any effects of radiation-exposure on outcomes, we may provide etiological clues for MGUS and its progression to MM, or, even if we could not, we may provide the Japanese-specific prevalence of MGUS and its progression. The target population included atomic bomb survivors living in Nagasaki City as of October 1, 1988 (N=71,062; median age 58 years at 1988; range 42 to 97). The screening process consisted of agarose-gel electrophoresis, immuno-electrophoresis and quantitative immunoglobulin. General laboratory test and physical examination were also conducted. Serum samples were obtained from 52,525 subjects (73.9% of population) during October 1, 1988 to March 31, 2004. We identified 1,087 cases of MGUS among screened subjects. The crude prevalence of MGUS was 2.1% (95%CI, 1.9 to 2.2) in all subjects, and was 2.4% when limited subjects 50 years or older at 1988. MGUS prevalence increased by age same as many previous studies had reported. The prevalence was significantly higher in men than in women (2.8% vs. 1.6%, odds ratio 1.7, 95%CI, 1.5–1.9). To investigate the effect of radiation-exposure on occurrence of MGUS, a multiple logistic regression analysis, adjusted for age-at-1988 and sex, were performed including three radiation exposed-states: exposed within 1.5km from the atomic bomb hypocenter, 1.5–3.0km, and beyond 3.0km. There was a significant interaction between age-at-1988 and the exposed distance. We suspected that age at exposed to radiation might influence the occurrence of MGUS. Therefore, we performed multiple logistic regressions separately by dichotomized exposed age at 1945, under 20 years or 20 years or more, including sex, age-at-1988 (every 10 years as continuous data), and exposed distance category as covariates. In both age groups, male sex and the aging were strong risk factors of occurrence of MGUS. The exposed distance was not affected in exposed age 20 years or more at 1945. However, in exposed age under 20 years at 1945, MGUS prevalence was higher in those exposed within 1.5km than those beyond 3.0km (adjusted OR=1.4, 95%CI, 1.7–2.4, p&lt;0.0001). Among MGUS cases, 38 cases developed to MM during the follow-up. Overall cumulative risk of MM from MGUS was 8% during the average follow-up period 4.6 years. The estimated cumulative risk of developing MM was not different in sex, exposed age, and exposed distance, though those exposed proximally tend to develop to MM earlier than those exposed distally. Our results suggest that the higher radiation exposure at the younger age may affect the occurrence of MGUS beyond the effect of aging and sex on it, but the effect was weak for the progression from MGUS to MM. Further population-based studies for people exposed to radiation and external analyses are needed to confirm these findings.