Obesity and the Transformation of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma: A Population-Based Cohort Study

Chang, Su‐Hsin; Luo, Suhong; Thomas, Tanya; O’Brian, Katiuscia; Colditz, Graham A.; Carlsson, Nils P.; Carson, Kenneth R.

doi:10.1093/jnci/djw264

Cited by 66 publications

(50 citation statements)

References 36 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although our results are limited by the small number of cases and should be interpreted with caution, the consistently high risk 42 strengthens the notion that obesity plays a role in myelomagenesis and is possibly the first identified modifiable risk factor for progression of MGUS to MM. We did not find body weight or body composition at study baseline in MGUS/LC-MGUS cases to be risk factors for progression to MM and other LP diseases.…”

Section: Discussionsupporting

confidence: 77%

“…A study on a cohort of US veterans within the Veterans Health Administration system found an increased risk of MM to be associated with both overweight (HR, 1.55; 95% CI, 1.16-2.06) and obesity (HR, 1.98; 95% CI, 1.47-2.68) at MGUS diagnosis. 42 We thus speculate that the observed risk of MM in individuals with obesity is not because of increased risk of MGUS, but rather that they have similar MGUS prevalence but a higher risk of progression.…”

Section: Discussionmentioning

confidence: 78%

See 1 more Smart Citation

Obesity and risk of monoclonal gammopathy of undetermined significance and progression to multiple myeloma: a population-based study

et al. 2017

View full text Add to dashboard Cite

Key Points• Obesity is not associated with MGUS or LC-MGUS.• High body mass index during midlife is associated with increased risk of progressing from MGUS and LC-MGUS to MM and other LP diseases.All multiple myeloma (MM) cases are preceded by the premalignant state monoclonal gammopathy of undetermined significance (MGUS). Results from previous studies show a positive association between obesity and MM; however, the association between obesity and MGUS is controversial. The aims were to determine (1) if obesity is associated with an increased risk of MGUS and light-chain MGUS (LC-MGUS) and (2) whether obesity is associated with a higher risk of progression to MM and other lymphoproliferative (LP) diseases. Data from the population-based Age, Gene/Environment Susceptibility-Reykjavik Study (N 5 5764) were used. We performed serum protein electrophoresis and serum free light-chain assay on all subjects to identify MGUS and LC-MGUS cases. We included 11 different measures on current and previous obesity in our analysis. Logistic regression andCox proportional-hazard regression were used to analyze the associations. A total of 300 (5.2%) MGUS and 275 (4.8%) LC-MGUS cases were identified. During a median follow-up of 8 years, 18 had progressed to MM and 11 to other LP diseases. We found no association between the 11 obesity markers and MGUS or LC-MGUS (odds ratios 0.81 to 1.15 for all 11 variables in both conditions). Interestingly, we found that high midlife body mass index increased risk of progression to MM and other LP diseases (hazard ratio, 2.66; 95% confidence interval, 1.17-6.05). To conclude, obesity was not associated with MGUS. However, we found overweight/obesity to be a risk factor for progression from MGUS to MM and other LP diseases, suggesting that obesity plays a role in the transformation of MGUS to MM.

show abstract

Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 78%

Obesity and risk of monoclonal gammopathy of undetermined significance and progression to multiple myeloma: a population-based study

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Obesity has been strongly associated with precancerous lesions and conditions such as colon adenomas [68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86], monoclonal gammopathy [87][88][89][90][91][92][93][94][95][96][97][98], chronic pancreatitis [99][100][101][102], or inflammatory bowel disease (IBD) [103][104][105][106]. Observed risks of cancers associated with obesity include breast [107][108][109][110][111], colorectal [112][113][114][115], pancreatic [99]…”

Section: Morbid Obesitymentioning

confidence: 99%

Microbiome and morbid obesity increase pathogenic stimulus diversity

Brücher

Jamall

2019

4open

View full text Add to dashboard Cite

The microbiome, the relationship between environmental factors, a high-fat diet, morbid obesity, and host response have been associated with cancer, only a small fraction of which (<10%) are genetically triggered. This nongenetic association is underpinned by a worldwide increase in morbid obesity, which is associated with both insulin resistance and chronic inflammation. The connection of the microbiome and morbid obesity is reinforced by an approximate shift of about 47% in the estimated total number of bacteria and an increase from 38,000,000,000,000 in a reference man to 56,000,000,000,000 in morbid obesity leading to a disruption of the microbial ecology within the gut. Humans contain 6,000,000,000 microbes and more than 90% of the cells of the human body are microorganisms. Changes in the microflora of the gut are associated with the polarization of ion channels by butyrate, thereby influencing cell growth. The decrease in the relative proportion of Bacteroidetes together with a change in the fermentation of carbohydrates by bacteria is observed in morbid obesity. The disruption of homeostasis of the microflora in the obese changes signaling and crosstalk of several pathways, resulting in inflammation while suppressing apoptosis. The interactions between the microbiome and morbid obesity are important to understand signaling and crosstalk in the context of the progression of the six-step sequence of carcinogenesis. This disruption of homeostasis increases remodeling of the extracellular matrix and fibrosis followed by the none-resolvable precancerous niche as the internal pathogenic stimuli continue. The chronic stress explains why under such circumstances there is a greater proclivity for normal cells to undergo the transition to cancer cells.

show abstract

“…The shortening of the latent period from benign to malignant disease in association with obesity has been most clearly demonstrated at the clinical level, where disease-associated monoclonal immunoglobulin provides a biomarker for early detection and demonstration that obesity accelerates the conversion of monoclonal gammopathy of unknown significance (MGUS) to multiple myeloma (MM) (29). In further support of this proposal that obesity does not initiate but rather promotes cancer progression, almost all murine models in which obesogenic diets and DIO promote tumors require experimental utilization of genetically modified animals containing cancer-predisposing genes or transplantation of preexisting tumor cell lines (5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

Section: Systems Demonstrating That Obesity Promotes and Accelerates mentioning

confidence: 99%

Young Adult Cancer: Influence of the Obesity Pandemic

Berger

2018

Obesity

View full text Add to dashboard Cite

Cancer in young adults is occurring with increasing frequency. Overweight and obesity have become major public health issues reaching pandemic proportions. Excess weight is associated with increased cancer risk, morbidity, and mortality. Multiple murine models indicate that obesity not only increases cancer incidence but also accelerates its development. Thus, the possibility exists that overweight and obesity may be contributing to the appearance of specific malignancies at younger ages. This prospect, in association with the worldwide expansion of obesity, suggests an impending explosive increase in obesity-associated cancers in young adults.

show abstract

Obesity and the Transformation of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma: A Population-Based Cohort Study

Abstract: Obesity and black race are risk factors for transformation of MGUS to MM. Future clinical trials should examine whether weight loss is a way to prevent the progression to MM in MGUS patients.

Cited by 66 publications

References 36 publications

Obesity and risk of monoclonal gammopathy of undetermined significance and progression to multiple myeloma: a population-based study

Obesity and risk of monoclonal gammopathy of undetermined significance and progression to multiple myeloma: a population-based study

Microbiome and morbid obesity increase pathogenic stimulus diversity

Young Adult Cancer: Influence of the Obesity Pandemic

Contact Info

Product

Resources

About