Risk factors for monoclonal gammopathy of undetermined significance: a systematic review

Abstract

Monoclonal gammopathy of undetermined significance (MGUS), precursor of multiple myeloma, is an asymptomatic plasma cell disorder that overproduces serum monoclonal protein. Older age, male sex, black race, and family history of MGUS increase the risk of MGUS, yet other risk factors are known. We systematically reviewed observational epidemiological studies that examined sociodemographic, clinical, and behavioral risk factors for the development of MGUS. The protocol for this study was registered on the PROSPERO registry for systematic reviews. We identified epidemiological studies from PubMed and Scopus. Articles were limited to those written in English and published before February 2019. Five case-control and three cohort studies were eligible for data extraction. Studies evaluating factors associated with MGUS risk are limited, with conflicting conclusions regarding risk associated with obesity. Despite the limited research, a significant elevated risk for being diagnosed with MGUS was associated with several specific prior infections, inflammatory disorders, and smoking. The sparse existing literature suggests an increased risk of MGUS associated with several risk factors related to immune function. Further research is needed to explore the potential mechanisms underlying the development of MGUS and to confirm risk factors, both modifiable and non-modifiable.

Keywords: MGUS; Risk factors; Systematic review.

Fig. 1

PRISMA flow diagram

Fig. 2

Forest plot of reported associations of MGUS with sociodemographic factors from the published literature. (a) Landgren et al. (2010)—adjusted for age, race/ethnicity, household size, obesity, and annual household income. (b) Pasqualetti et al. (1996)—analysis matched by sex and age

Fig. 3

Forest plot of reported associations of MGUS with medical conditions from the published literature. (a) Adjusted for number of visits, race, latency, attained age, and calendar time [27].(b) Adjusted for year of birth (in quartiles), year of diagnosis (in quartiles), and sex [29]. (c) Adjusted for diabetes, smoking, obesity, hypertension, hyperlipidemia, coronary artery disease, and autoimmune disease.*Also adjusted for prior laboratory tests [26]. (d) Adjusted for age, race/ethnicity, household size, obesity, and annual household income [28]. (e) Adjusted for age and sex [32]

Fig. 4

Forest plot of reported associations of MGUS with behavioral factors from the published literature. (a) Adjusted for diabetes, smoking, obesity, hypertension, hyperlipidemia, coronary artery disease, and autoimmune disease [26]. (b) Matched analysis sex and age [30]. (c) Adjusted for age and gender [31]. (d) Adjusted for age, sex, and other group of food [33]