Diabetes and the risk of non-Hodgkin's lymphoma and multiple myeloma in the European Prospective Investigation into Cancer and Nutrition

Khan, Aneire; Gallo, Valentina; Linseisen, Jakob; Kaaks, Rudolf; Rohrmann, Sabine; Raaschou‐Nielsen, Ole; Tjønneland, Anne; Johnsen, Hans E.; Overvad, Kim; Bergmann, Manuela M.; Boeing, Heiner; Benetou, V.; Ψαλτοπούλου, Θεοδώρα; Trichopoulou, Antonia; Masala, Giovanna; Mattiello, Amalia; Grioni, Sara; Tumino, Rosario; Vermeulen, Roel; Peeters, Petra H.; Bueno-de-Mesquita, H. Bas; Ros, Martine M.; Lund, Eiliv; Ardanaz, Eva; Chirlaque, M-D; Jakszyn, Paula; Larranaga, N.; Losada, A.; Becker, Nikolaus; Nieters, A.; Martínez‐García, Carmen; Ågren, Anneli; Hallmans, Göran; Berglund, Göran; Manjer, Jonas; Allen, Naomi E.; Key, Tim; Bingham, Sheila; Khaw, Kay Tee; Slimani, Nadia; Ferrari, Pietro; Boffetta, Paolo; Norat, Teresa; Víneis, Paolo; Riboli, Elio

doi:10.3324/haematol.12297

Cited by 44 publications

(37 citation statements)

References 46 publications

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“…Although results in the literature are contradictory, in a recent study conducted by Khan et al (2008) there was no association between self reported diabetes and multiple myeloma whereas the highest level of postload glucose was associated with risk of mortality from multiple myeloma (HR, 3.06; 95% CI, 1.05-8.93) in another study by Chiu et al (2006). This is in contrast with observations of other studies based in Asia (Vineis et al 2000).…”

Section: Resultscontrasting

confidence: 56%

Multiple Myeloma - A hospital based cross sectional study in Bangladesh

Choudhury

Sultana

Islam

et al. 2013

J. Asiat. Soc. Bangladesh, Sci.

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Bone marrow morphological examination was performed on 835 patients either admitted in the inpatient departments of BIRDEM General Hospital or examined on outpatient basis. 760 of them were adults and 75 of them were children. 74 of the patients were diagnosed as suffering from a blood cancer known as Multiple Myeloma (MM). The age range of MM in our study was 40 to 85 years with a mean age of 63.25 years. Male to female ratio was 5:2 with a slight male preponderance. The median age of presentation was lower in females (60 years) than in males (65 years). MM was the second most frequent haematological disorder among all the patients examined, the most frequent one being leukemia. The frequency of MM was slightly higher among patients admitted in BIRDEM Hospital (10.4%) than those examined on outpatient basis (8.3%) although the difference was not statistically significant (P = 0.379 by Pearson's Chi square test). The highest frequency of MM was found in patients admitted in the department of Orthopaedic Surgery (20.8%) followed by the Department of Nephrology (16.7%). This data represents a cross sectional picture of the prevalence of MM in elderly population.

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Section: Resultscontrasting

confidence: 56%

Multiple Myeloma - A hospital based cross sectional study in Bangladesh

Choudhury

Sultana

Islam

et al. 2013

J. Asiat. Soc. Bangladesh, Sci.

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“…Three studies provided data on PTCL. 16,27,30 The OR for PTCL was 2.42 (95% CI, 1.24-4.72; P ϭ .009; I 2 ϭ 0%; supplemental Figure). There was an association seen in Asian (OR ϭ 3.21, 95% CI, 1.14-8.44; P ϭ .03) but not in European studies.…”

Section: Outcome Resultsmentioning

confidence: 99%

“…Four studies provided data on DLBCL and FL. 12,16,26,28 The OR for DLCBL was 1.16 (95% CI, 0.92-1.48; P ϭ .22; I 2 ϭ 28%). There was an association in European studies (OR ϭ 1.48, 95% CI, 1.10-2.01; P ϭ .01; I 2 ϭ 0%), but not in American studies.…”

Section: Outcome Resultsmentioning

confidence: 99%

“…Eleven studies reported data on the association between DM2 and leukemia. 10,13,15,16,19,20,22,24,27,33,34 Six studies reported data on leukemia in general, 10,13,15,19,20,22 3 studies on chronic lymphocytic leukemia (CLL), 16,24,27 and 2 studies on either myeloid or lymphoid leukemia. 33,34 The OR of leukemia in patients with DM2 was 1.22 (95% CI, 1.03-1.44; P ϭ .02; Figure 2).…”

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confidence: 99%

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Increased incidence of non-Hodgkin lymphoma, leukemia, and myeloma in patients with diabetes mellitus type 2: a meta-analysis of observational studies

Castillo

Mull

Reagan

et al. 2012

Blood

194

139

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Hematologic malignancies are a heterogeneous group of conditions with an unclear etiology. We hypothesized that diabetes mellitus type 2 is associated with increased risk of developing lymphoma, leukemia, and myeloma. A literature search identified 26 studies (13 casecontrol and 13 cohort studies) evaluating such an association. Outcome was calculated as the odds ratio (OR) using a random effects model. Heterogeneity and publication bias were evaluated using the I 2 index and the trim-and-fill analysis, respectively. Quality was assessed using the Newcastle-Ottawa scale. The OR for non-Hodgkin lymphoma was increased at 1.22 (95% confidence interval [CI], 1.07-1.39; P < .01) but the OR for Hodgkin lymphoma was not. There was an increased OR for peripheral T-cell lymphoma (OR ‫؍‬ 2.42, 95% CI, 1.24-4.72; P ‫؍‬ .009) but not for other non-Hodgkin lymphoma subtypes. The OR for leukemia was 1.22 (95% CI, 1.03-1.44; P ‫؍‬ .02) and the OR for myeloma was 1.22 (95% CI, 0.98-1.53; P ‫؍‬ .08). Although diabetes mellitus type 2 seems to increase the risk of developing lymphoma, leukemia, and myeloma, future studies should focus on evaluating other potential confounders such as obesity, dietary habits, physical activity, and/or antidiabetic therapy. IntroductionHematologic malignancies are a heterogeneous group of diseases characterized by the malignant uncontrolled growth of hematopoietic cells. According to Surveillance Epidemiology and End Results data, approximately 75 000, 45 000, and 20 500 persons were diagnosed with lymphoma, leukemia, and myeloma, respectively, in 2011 in the United States alone. 1 The development of hematologic malignancies has been associated with different causes, such as infectious processes (eg, HTLV-1 and adult T-cell leukemia/lymphoma), autoimmune disorders (eg, rheumatoid arthritis, Sjogren syndrome, and systemic lupus erythematosus) or a positive family history. However, despite recent advances in the understanding of their pathophysiology, the etiology of these conditions remains largely unexplained.Diabetes affects approximately 25.8 million people in the United States. 2 It is estimated that diabetes mellitus type 2 (DM2) accounts for 90%-95% of all diabetes cases. DM2 has been studied as a potential risk factor for the development of hematologic malignancies; however, studies evaluating such an epidemiologic association have rendered conflicting results. In a previous metaanalysis evaluating the association between diabetes and incidence of lymphoma, 3 we found a stronger association for DM2 and non-Hodgkin lymphoma (NHL). However, NHL subtype analyses were not performed given the paucity of the data available at the time.The primary objective of the present study was to evaluate the potential association between DM2 and the incidence of lymphoma, leukemia, and myeloma. Secondary objectives were to evaluate the association between DM2 and specific subtypes of lymphoma and leukemia. Methods Literature searchTwo authors performed a literature search independently using PubMed/ MEDLINE a...

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“…In addition, exposure to a wide range of toxins as well as type 2 diabetes (T2D) and obesity have been suggested as important mediators of the complex process of myelomagenesis (Alexander et al 2007, Lope et al 2008, Wallin & Larsson 2011. Among these latter preventable factors, T2D has attracted significant attention since it has been consistently identified as a medical condition frequently found in MM patients (Khan et al 2008, Richardson et al 2009, Castillo et al 2012 and it is thought to influence the myelomagenesis through hyperglycaemia and insulin-dependent and -independent mechanisms (Xu et al 2014). In a recent well-powered meta-analysis, Castillo et al (2012) observed that T2D was significantly associated with an increased risk of developing the disease (Castillo et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium

Lupiañez¹,

Campa²,

Martino³

et al. 2015

Endocrine-Related Cancer

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Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case-control study including 1420 MM patients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1 rs2237892T allele or the CDKN2A-2B rs2383208G/G , IGF1 rs35767T/T and MADD rs7944584T/T genotypes had a significantly increased risk of MM (odds ratio (OR)Z1.32-2.13) whereas those carrying the KCNJ11 rs5215C , KCNJ11 rs5219T and THADA rs7578597C alleles or the FTO rs8050136A/A and LTA rs1041981C/C genotypes showed a significantly decreased risk of developing the disease (ORZ0.76-0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)Z0.645 vs AUCZ0.629; PZ4.05! 10 K06). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30 rs2641348 and NOTCH2 rs10923931 variants (P interaction Z0.001 and 0.0004, respectively). Men carrying the ADAM30 rs2641348C and NOTCH2 rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (OR M Z0.71 and OR M Z0.66 vs OR W Z1.22 and OR W Z1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models.

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Diabetes and the risk of non-Hodgkin's lymphoma and multiple myeloma in the European Prospective Investigation into Cancer and Nutrition

Cited by 44 publications

References 46 publications

Multiple Myeloma - A hospital based cross sectional study in Bangladesh

Multiple Myeloma - A hospital based cross sectional study in Bangladesh

Increased incidence of non-Hodgkin lymphoma, leukemia, and myeloma in patients with diabetes mellitus type 2: a meta-analysis of observational studies

Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium

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