Obesity and the Risk of Non-Hodgkin's Lymphoma – A Meta-Analysis Involving More Than 40,000 Cases

Obesity is linked with altered immune function and chronic inflammatory response; multiple studies have related autoimmune and chronic inflammatory processes with an increased risk of non-Hodgkin's lymphoma. However, epidemiological studies on the relation between excess body weight and risk of non-Hodgkin's lymphoma have yielded inconsistent results. The objective of this study is to examine the relationship between obesity, as measured by body mass index (BMI), and risk of non-Hodgkin's lymphoma in a meta-analysis of epidemiological studies.

We performed a comprehensive search of MEDLINE, EMBASE and CINAHL databases for studies on BMI and non-Hodgkin's lymphoma that were published from 1966 to June 2010. Search terms included body mass index, BMI, or obesity combined with lymphoma. The reference lists of identified articles were manually reviewed to identify additional papers. Key Inclusion Criteria - cohort or case–control studies reporting NHL incidence or mortality as an outcome, BMI (body weight in kilograms divided by the square of height in meters) as the exposure of interest, and relative risks (RRs) or odds ratios with their 95% confidence intervals (CIs) as the outcome measures. Data Extraction and Statistical analysis - Two reviewers independently extracted study information and data. Where multiple outcome measures were reported, the most adjusted for was used. Before analysis, all studies were tested for publication bias using the Begg's and Egger's test. Pooled RRs with 95% confidence intervals (CI) were calculated using the random-effects meta-analysis model if heterogeneity was present; otherwise, the fixed-effects model was used. All statistical analyses were performed using Stata software, version 9.0 (Stata-Corp, College Station, TX).

Twenty-five studies (17 cohort and 8 case-control studies) with 40,279 participants met the inclusion criteria. Compared to individuals with BMI < 25.0 kg/m2, the summary RRs for non-Hodgkin's lymphoma were 1.05 (95% CI, 1.01–1.10) and 1.15 (95% CI, 1.06–1.25) for overweight (BMI between 25 and 30 kg/m2) and obese (BMI > 30.0 kg/m2) individuals respectively. By histological subtypes, obesity was associated with a statistically significant increase risk of diffuse large B-cell lymphoma (RR, 1.23; 95% CI, 1.11–1.37; n = 13 studies) but not with follicular lymphoma (RR, 1.11; 95% CI, 0.97–1.27; n = 13 studies) or small lymphocytic lymphoma/chronic lymphocytic leukemia (RR, 0.95; 95% CI, 0.84–1.07; n = 8 studies). There was no evidence of publication bias.

The results of this meta-analysis suggest that compared to normal weight individuals, overweight and obese individuals have a 5% and 15% increased risk of non-Hodgkin's lymphoma respectively. Though statistically significant, these proportions are relatively small and perhaps may be accounted for by residual confounding. Larger, long term prospective studies will be needed to conclusively define the magnitude and strength of the association between body weight and non-Hodgkin lymphoma.

Off Label Use: High dose Melphalan is not FDA approved as conditioning regimen for Autologous stem cell transplant.