Introduction
Overweight and obesity have consistently been acknowledged as contributing factors to various common cancers. Recently, the World Health Organization (WHO) concluded that weight plays a significant role in 13 types of cancer, including multiple myeloma (MM). Obesity is considered a precursor to blood cancer. New research published in Blood Advances indicates that individuals who are obese have a higher likelihood of developing monoclonal gammopathy of undetermined significance (MGUS). This non-cancerous blood condition often precedes multiple myeloma.
Multiple myeloma is a type of blood cancer affecting plasma cells, which are white blood cells responsible for producing antibodies to combat infections. MGUS is characterized by abnormal proteins produced by plasma cells and is recognized as a precursor to multiple myeloma. Although most individuals with MGUS do not experience significant symptoms and are not immediately ill, the presence of MGUS serves as a cautionary sign to monitor for potential progression to more serious conditions, such as multiple myeloma. This article explains the connection between obesity and cancer.
What Is Multiple Myeloma?
MM is characterized by a chronic B-cell disorder marked by abnormal plasma cell proliferation in the bone marrow. Every instance of MM is preceded by a premalignant condition called monoclonal gammopathy of undetermined significance (MGUS), with an asymptomatic presence of an M-protein in the serum. MGUS prevalence rises with age, affecting around five percent of individuals above 70 years, with an estimated one percent yearly risk of progressing to MM.
Light-chain MGUS (LC-MGUS) has recently been identified as a precursor to light-chain MM, defined by an abnormal free light-chain (FLC) ratio without heavy chain expression. The etiology of MGUS and LC-MGUS remains largely unknown, though certain risk factors such as male gender, black ethnicity, family history of related diseases, and prior immune-related conditions have been associated.
Obesity has been recognized as a risk factor for MM, with meta-analyses indicating a 10 to 20 percent increased risk for every 5 kg/m² increase in body mass index (BMI). However, BMI alone might not suffice, as it does not account for fat distribution, which is crucial given that obesity-related complications are closely linked to abdominal fat. Recent studies suggest waist circumference is a significant risk factor for MM mortality, especially when considering BMI in early adulthood, particularly in women. Furthermore, recent research indicates that patients with MM tend to have higher abdominal fat compared to those with MGUS, hinting at its potential as a biomarker for progression from MGUS to MM. The exact biological mechanisms through which obesity influences MM development are still uncertain.
Proposed mechanisms include the effects of interleukin-6 (IL-6), insulin-like growth factor 1, and adiponectin. Obesity can result in elevated IL-6 levels, a growth factor in MM, as a considerable portion of IL-6 is produced by adipose tissue. Elevated levels of bioavailable insulin-like growth factor 1 due to obesity may stimulate MM cell proliferation and impede apoptosis. Additionally, lower levels of adiponectin in obese individuals have been associated with higher MM risk and progression from MGUS to MM.
Is Obesity a Precursor for Blood Cancer?
Multiple myeloma is a type of blood cancer affecting plasma cells that are responsible for producing antibodies to fight infections. MGUS is a precursor to multiple myeloma, characterized by abnormal protein production in plasma cells. While MGUS usually shows no noticeable symptoms, it is a warning sign to monitor for more serious conditions, like multiple myeloma.
Obesity, with a BMI of 30 or higher, is prevalent in about 42% of the US population. Despite this, little research has explored how obesity might impact cancer outcomes. Dr. David Lee, an internal medicine resident, emphasizes that multiple myeloma remains incurable and is often diagnosed after significant organ damage has occurred. His research focuses on identifying risk factors for MGUS and understanding its progression to multiple myeloma.
Dr. Lee's team studied 2,628 individuals at high risk of multiple myeloma, finding that obesity was associated with a 73% higher likelihood of having MGUS. Even after adjusting for physical activity, the association between obesity and MGUS remained strong. However, highly active individuals were less likely to have MGUS. It is important to note that this study was cross-sectional, providing a snapshot rather than causal evidence.
Additionally, BMI alone may not accurately assess healthy weight, especially across ethnic groups. Moving forward, researchers aim to validate these findings and explore how lifestyle factors like weight, exercise, and smoking influence MGUS development and progression. Understanding these relationships could lead to effective preventative strategies for diseases like multiple myeloma. The underlying mechanisms behind cancer initiation and recurrence in individuals with obesity are complex and varied across different types of cancer and remain incompletely understood.
Further research is necessary to comprehensively grasp the specific pathways involved in each cancer type and pinpoint potential primary and secondary cancer prevention targets. Although numerous studies have highlighted a correlation between obesity and adverse cancer outcomes, there is a need for additional investigations utilizing innovative clinical and molecular markers. Current literature faces limitations such as reliance on a fixed BMI threshold of 30 kg/m² to categorize individuals as obese or non-obese, inadequate information regarding the timing of obesity onset, and a lack of adjustment for various psychosocial, genetic, environmental, and behavioral factors. Given the constraints associated with conventional anthropometric measurements, the regular integration of novel techniques for accurately assessing body fat and its distribution is crucial for future research exploring the intersection of cancer and obesity.
Conclusion
In conclusion, it can be said that the leptin and other chemokines of individuals with obesity facilitate the movement of bone marrow-derived monocytes into adipose tissue. This process leads to increased levels of inflammatory cytokines like IL-6 and TNF-α. Consequently, there is a rise in acute phase proteins such as CRP, contributing to chronic low-grade inflammation.
This inflammation can affect hematologic parameters and influence the risk of thrombosis. Although it is hypothesized that bone marrow-derived monocytes produce and respond to pro-inflammatory signals, this mechanism remains unclear in current literature. Further research could unveil potential therapeutic targets earlier in the inflammatory response pathway.
