Monoclonal gammopathy of undetermined significance in atomic bomb survivors: incidence and transformation to multiple myeloma

Abstract

Summary. Among 6737 atomic bomb survivors who did not have monoclonal gammopathy at the first examination, 112 developed monoclonal gammopathy of undetermined significance (MGUS) between 1985 and 2001. The crude incidence rate was 164 per 100 000 person-years in the overall study population, with a sharp increase in incidence after age 60 years. The incidence was not significantly associated with radiation dose (P ¼ 0AE91), although the incidence at less than 80 years of age showed a marginally significant association (P ¼ 0AE05). Among 75 patients with MGUS detected in 1985, 50 patients (67%) had died by 2001, 16 (21%) of these deaths were due to multiple myeloma (MM). MM mortality among MGUS patients was 2284 per 100 000 person-years while the rate in the total population was 14AE6 per 100 000 person-years. The risk of MM mortality was greater in the older generation. The transformation from MGUS to MM was faster in exposed persons than in non-exposed persons, but this was not statistically significant.

Relationship between monoclonal gammopathy of undetermined significance and radiation exposure in Nagasaki atomic bomb survivors

“…Neriishi et al reported no association between radiation dose (DS86) and the incidence of 112 (1.7%) cases of MGUS among 6737 atomic bomb survivors who were members of the Adult Health Study (AHS) of RERF. 13 The study found that the MGUS risk was not different between those exposed to more than 0.01 Gy and those exposed to less than 0.01 Gy (relative risk [RR] ϭ 1.35; 95% CI, 0.9-2.0). There were several differences between the AHS study and the present study in terms of analytic method and observed results.…”

“…12 However, a small survey for atomic bomb survivors showed no association between radiation dose and the relative risk of MGUS. 13 Sample sizes of these previous studies were too small to obtain reliable results for association between radiation exposure and incidence of the disease.…”

Multiple myeloma: A review of the epidemiologic literature

“…Neriishi et al 175 examined the incidence of MGUS and its transformation to multiple myeloma in atomic bomb survivors, and a significant exposure-response relationship was not evident between radiation dose and incidence of MGUS. Transformation from MGUS to multiple myeloma occurred in 16% of the nonexposed persons, 17% of the dose-unknown persons and 26% of the exposed persons.…”

“…It appeared that the onset of multiple myeloma transformation from MGUS was accelerated in radiation-exposed persons compared to nonexposed persons. 175 Unlike atomic bomb survivors who received acute exposures to high doses of radiation, workers in the nuclear industry or other radiation-exposed occupational cohorts receive chronic exposures at presumably lower doses over a working lifetime. In an early study, Cuzick 176 reported a significantly increased relative risk among pooled occupational cohorts with exposures to radiation (RR 5 2.05, 95% CI: 1.4-2.9); however, recent studies among occupational cohorts have not confirmed these findings.…”

Gene-expression signature of benign monoclonal gammopathy evident in multiple myeloma is linked to good prognosis

“…5,6 A long latency phase of 15 to 20 years passed before an increase in MM incidence was documented in Japan as a result of the nuclear fallout from the atomic bombs. 7 Thus, it is plausible to assume that younger patients are likely to develop MM acutely, whereas a smoldering clinical course has been frequently documented to precede the onset of symptomatic MM in the elderly. Smoldering MM (SMM) can be considered an advanced phase of MGUS; even at the time of progression, SMM-evolved MM usually lacks osteolytic lesions or other cardinal features of symptomatic MM.…”