First-degree relatives of patients with multiple myeloma (MM) appear to have a significantly higher risk of monoclonal gammopathy of undetermined significance (MGUS) compared to the general population, regardless of age, gender, or tumor characteristics, according to a study published in Leukemia. Researchers noted that MGUS generally progresses to symptomatic MM at a rate of 1% per year; thus, in selected cases, screening of first-degree relatives of individuals with MM may be worth considering for follow-up and prevention strategies.
In this study, 400 patients with MM and 30 patients with smoldering MM were recruited between 2005 and 2015, and 1179 serum samples were obtained from first-degree relatives over age 40 for evaluation of MGUS. The researchers compared age- and sex-specific rates of MGUS among first-degree relatives with rates of MGUS in a population-based sample.
The researchers detected MGUS in 75 first-degree relatives, yielding an age-adjusted and sex-adjusted prevalence of 5.8%. Prevalence of MGUS in first-degree relatives was 2.4 times greater than that in the general population. Familial risk did not differ with the proband’s age at diagnosis, gender, isotype, IgH translocation, or trisomy.
In this study, 97% of the probands were white and 56% were male. Of the patients’ first-degree relatives, 58.7% were female and 62.8% were siblings. The researchers theorized that familial clustering of MM and MGUS in these families may “likely be due at least in part to shared germline variation.” However, despite ﬁndings of LSD1/KDM1A mutations among early onset cases, this study’s findings “did not support increased familial risk by early age of onset,” the authors concluded. Furthermore, the study did not reveal any strong evidence for differences in familial MGUS by clinical MM subtypes or tumor characteristics.
The researchers concluded that future studies will need to include more detailed germline and tumor sequencing data.
1. Clay-Gilmour AI, Kumar S, Rajkumar SV, et al. Risk of MGUS in relatives of multiple myeloma cases by clinical and tumor characteristics [published online September 10, 2018]. Leukemia. doi: 10.1038/s41375-018-0246-2