Obesity shown not to be a risk factor for occurrence of MGUS, but does affect progression from MGUS to MM

Obesity is now a well-recognized risk factor for most types of cancer, including Multiple Myeloma (MM). In fact, one study has specifically shown that for MM, there is a 10–20% increased risk for every 5kg/m² increase in body mass index (BMI). However, BMI does not take into account fat distribution, and a patient’s waist circumference is argued to be a more relevant factor. The biological link connecting obesity with MM could be due to increased expression of IL6 from adipose tissue, an established growth factor in MM, as well as enhanced levels of insulin-like growth factor 1, which has been linked with MM cell proliferation and inhibition of apoptosis. Therefore, obesity is theoretically a very valid risk factor.

MM is preceded by the asymptomatic and precursor state of monoclonal gammopathy of undetermined significance (MGUS), but the link between this condition and obesity remains a matter of debate. In a study conducted by Sigurdur Kristinsson from the Faculty of Medicine, University of Iceland, Reykjavik, and published in Blood Advances in November 2017, the association between 11 different obesity measures and MGUS, as well as a distinct form of MGUS in which free light chains occurs in abundance without the presence of a heavy chain (LC-MGUS), were analyzed. In addition, the data were analyzed in order to establish whether obesity was a risk factor for progression of MGUS and LC-MGUS to MM.

Key Highlights:

• Total of 5,725 participants included in the analysis from the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-RS); 39 (0.7%) people were excluded from analysis due to various reasons
• Mean age = 77 years (range 66-98)
• MGUS was defined as the appearance of 1 or several M-protein bands on SPEP and an M-protein concentration of <30 g/L and was identified in 300 subjects (5.2%)
• LC-MGUS was defined as no M-protein band visible on SPEP and a pathological FLC ratio (<0.26 or >1.65) on FLC analysis in combination with an increased concentration of the relevant light chain (f-k >19.4 mg/L, f-l >26.3 mg/L) and was identified in 275 subjects (4.8%)
• Obesity was assessed using 11 different measures; baseline measures were: weight (kg), BMI (kg/m²), percent body fat (%), fat (kg), total body fat (cm²), visceral fat (cm²), subcutaneous fat (cm²), and 2 versions of abdominal circumference (cm), as well as self-reported lifetime maximum weight and measured midlife BMI (obtained from the Reykjavik Study data)
• There was no association found between the 11 obesity markers and MGUS or LC-MGUS; odds ratio of 0.81­‑1.15 for all 11 variables
• There was no significant increase in the risk of progression from MGUS or LC-MGUS to MM with high midlife BMI (>25 kg/m²): HR = 2.64; (95% CI, 0.93-7.48)
• High midlife BMI was associated with an increased risk of progression to MM or other lymphoproliferative (LP) diseases; HR = 2.66; (95% CI, 1.17-6.05)

Using a wide range of measures to define obesity in a large sample size (5,686), no association was found between MGUS and LC-MGUS. However, obesity was found to be a risk factor for progression to MM and other LP diseases. This is the first study to show the association with progression to MM, and this links with the conclusion issued by the World Health Organization (WHO) that there is a strong association between body fat and MM. However, it must be kept in mind that this was an Icelandic study and therefore excludes many ethnic groups.