Intake of total, classes, and subclasses of (poly)phenols and risk of lymphoid neoplasms: a prospective analysis in the EPIC cohort.

Reply to ‘Alcohol consumption and risk of Hodgkin's lymphoma and multiple myeloma: a multicentre case-control study’ by Gorini et al.

A family history of hematopoietic malignancy is associated with an increased risk of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), although the magnitude of the relative risk is unclear. We estimated the association between familial hematopoietic cancer and risk of lymphoma using validated, registry-based family data, and we also investigated whether associations between some environmental exposures and risk of lymphoma vary between individuals with and without such a family history. In a population-based case-control study of malignant lymphoma, 1506 case patients and 1229 control subjects were linked to the Swedish Multi-Generation Register and then to the Swedish Cancer Register to ascertain history of cancer in first-degree relatives of patients with malignant lymphoma. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with the risk of lymphoma. A history of hematopoietic malignancy in any first-degree relative was associated with an increased risk of all NHL (OR = 1.8, 95% CI = 1.2 to 2.5), common B-cell NHL subtypes, and HL. Relative risks were generally stronger in association with sibling hematopoietic cancer (OR for all NHL = 3.2, 95% CI = 1.3 to 7.6) than with parental hematopoietic cancer (OR = 1.6, 95% CI = 1.1 to 2.3). A family history of NHL or chronic lymphocytic leukemia (CLL) was associated with an increased risk of several NHL subtypes and HL, whereas familial multiple myeloma was associated with a higher risk of follicular lymphoma. There was no statistically significant heterogeneity in NHL risk associations with environmental factors between individuals with and without familial hematopoietic malignancy. The increased risk of NHL and HL among individuals with a family history of hematopoietic malignancy was approximately twofold for both lymphoma types. There was no evidence that etiologic associations varied between familial NHL and nonfamilial NHL.

Hepatitis C and Risk of Lymphoma: Results of the European Multicenter Case-Control Study EPILYMPH

Family History of Cancer and Risk of Lymphoma: Influence of IL8RB, GGH IVS7 and IL10 Polymorphisms.

Limited evidence exists on the role of modifiable lifestyle factors on the risk of lymphoma. In this work, the associations between adherence to healthy lifestyles and risks of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) were evaluated in a large-scale European prospective cohort. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 2,999 incident lymphoma cases (132 HL and 2,746 NHL) were diagnosed among 453,808 participants after 15 years (median) of follow-up. The healthy lifestyle index (HLI) score combined information on smoking, alcohol intake, diet, physical activity and BMI, with large values of HLI expressing adherence to healthy behavior. Cox proportional hazards models were used to estimate lymphoma hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses were conducted by excluding, in turn, each lifestyle factor from the HLI score. The HLI was inversely associated with HL, with HR for a 1-standard deviation (SD) increment in the score equal to 0.78 (95% CI: 0.66, 0.94). Sensitivity analyses showed that the association was mainly driven by smoking and marginally by diet. NHL risk was not associated with the HLI, with HRs for a 1-SD increment equal to 0.99 (0.95, 1.03), with no evidence for heterogeneity in the association across NHL subtypes. In the EPIC study, adherence to healthy lifestyles was not associated with overall lymphoma or NHL risk, while an inverse association was observed for HL, although this was largely attributable to smoking. These findings suggest a limited role of lifestyle factors in the etiology of lymphoma subtypes.

There are inconsistencies in the results of the studies investigating the association between inflammatory bowel disease (IBD) and lymphoma. The aim of this study is to systematically appraise the risk of lymphoma development in patients with IBD. We searched Embase, PubMed and Scopus from inception to 30 April 2024 to identify population-based cohort studies that evaluated the risk of lymphoma in patients with IBD in comparison with those without IBD. We carried out random-effects meta-analyses and estimated pooled relative risks (RRs) with 95% confidence intervals (CIs). We identified 23 eligible studies reporting 2078 lymphoma events in 656,731 patients with IBD. Patients with IBD had 30% higher odds of lymphoma (RR = 1.30 [95% CI: 1.21-1.40]). The risk of developing both Hodgkin's lymphoma (nine studies, RR = 1.29 [95% CI: 1.06-1.53]) and non-Hodgkin's lymphoma (16 studies, RR = 1.31 [95% CI: 1.20-1.42]) was increased in patients with IBD (p for interaction = 0.881). The increased risk of lymphoma was observed in both Crohn's disease (17 studies, RR = 1.54 [95% CI: 1.27-1.80]) and ulcerative colitis (20 studies, RR = 1.22 [95% CI: 1.09-1.35]) (p for interaction = 0.026). Meta-regression demonstrated that mean age of patients, study year, mean study follow-up duration, and percentages of immunomodulators and biologics use did not influence study outcome. The risk of lymphoma is only modestly increased in patients with IBD, with Crohn's disease having a slightly higher risk than ulcerative colitis. In IBD, there appears to be no difference between the risks of Hodgkin's and non-Hodgkin's lymphoma.

Investigators around the world have reported that incidence and mortality rates for non-Hodgkin lymphoma (NHL) increased steadily and substantially over the last five decades of the 20th century. Identifying what changes in the environment or in behavior fueled this epidemic still presents a major

Concerns have been raised about a possible excess risk of lymphomas in HIV-infected patients exposed to interleukin 2 (IL-2) therapy. Here we compared the risks of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) in IL-2-treated and IL-2-untreated HIV-infected patients. Patients monitored through the French Hospital Database on HIV between May 1, 1995, and December 31, 2005, were enrolled in this study. Lymphomas that occurred between the day after study entry and the end of follow-up were eligible for analysis. Poisson regression models were used in 2 separate analyses to quantify the possible relationship between IL-2 therapy and the incidence of NHL and HL. The IL-2-treated group consisted of 861 patients and the IL-2-untreated group of 77,605 patients. Follow-up lasted a total of 3643 and 382,720 person-years, respectively. After adjustment for sex and time-updated age, period, the CD4 cell counts, the plasma HIV RNA levels, and AIDS status, the relative rates of NHL and HL associated with IL-2 therapy were 0.64 (95% confidence interval, 0.25 to 1.65) and 0.33 (95% confidence interval, 0.04 to 2.86), respectively. In this large observational study, IL-2 therapy did not increase the risk of lymphoma, either NHL or HL, in HIV-infected patients.

Background: Non-Hodgkin Lymphoma (NHL) belong to the seventh most common cancer in Europe and constitute the tenth most commonly diagnosed cancer worldwide. Apart from risk factors such as certain infectious agents and immunodeficiency syndromes, genetic variants related to immunity have been associated with lymphomagenesis. Previous studies suggested an important role of the JAK-STAT signalling pathway in tumour development. Therefore, we explored genetic variants in the JAK-STAT pathway associated with lymphoma risk. Material and Methods: In total, 1481 lymphoma cases and 1491 age, sex and study centre matched controls of the EpiLymph study, a multi-centre case-control study on the aetiology of lymphomas among adults in Europe, were genotyped for 1536 single nucleotide polymorphisms (SNPs) using GoldenGate BeadArrayTM Technology (Illumina, San Diego, CA). Association between SNPs and haplotypes of the JAK-STAT pathway and risk of Hodgkin lymphoma (HL), NHL and most frequent NHL subtypes were estimated by calculating Odds Ratios (OR), the corresponding 95% confidence intervals (CI) and p-values using unconditional logistic regression (SAS 9.2). Results: Among 220 relevant SNPs, polymorphisms in several genes (STAT3, STAT6, IFNG, BMF, STAT5A) were significantly associated with lymphoma risk. Reduced risk for NHL overall and diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) were seen in association with seven STAT3 SNPs in high linkage disequilibrium and respective haplotypes. Variant rs4103200 conferred an about 20% reduced NHL risk (ORCG 0.79, 95% CI 0.66–0.94, ORGG of 0.78, 95% CI 0.66–0.91, ptrend=0.002). For DLBCL and FL a reduced risk with rs4103200 was also evident. A putatively functional variant in STAT6 previously associated with IgE levels (rs324011) was inversely associated with HL risk (ORTC/CC: 0.61, 95% CI 0.45–0.82, p=0.001). Conclusion: Our results implicate a relevant role of the JAK-STAT signalling in the development of lymphoma. Furthermore, our data support previously found associations between genetic variants of STAT genes and immune phenotypes.

Reply

Studies associate alcohol consumption, cigarette smoking, and body size with the risk of overall or subtype lymphoma. Current data come mostly from case-control studies or prospective studies with few cases. In the prospective National Institutes of Health-former American Association of Retired Persons (NIH-AARP) Diet and Health Study, the authors assessed the above lifestyle factors via baseline questionnaire among 285,079 men and 188,905 women aged 50-71 years and ascertained histologically confirmed Hodgkin's lymphoma (n = 58) and non-Hodgkin's lymphoma (n = 1,381) cases through linkage with cancer registries from 1995 to 2000. Compared with nondrinkers, alcohol consumers had a lower risk for non-Hodgkin's lymphoma overall (for >28 drinks/week: adjusted relative risk (RR) = 0.77, 95% confidence interval (CI): 0.59, 1.00; p(trend) among drinkers = 0.02) and for its main subtypes. Compared with never smokers, current smokers and recent quitters (<or=4 years ago) had higher risk of Hodgkin's lymphoma (RR = 2.25, 95% CI: 1.04, 4.89; RR = 4.20, 95% CI: 1.94, 9.09, respectively), whereas current or former smokers had lower risk of follicular non-Hodgkin's lymphoma (RR = 0.67, 95% CI: 0.52, 0.86). Severe obesity (body mass index of >or=35: RR = 1.29, 95% CI: 1.02, 1.64) and taller height (RR = 1.19, 95% CI: 1.03, 1.38) were associated moderately with non-Hodgkin's lymphoma. These findings add to the evidence that lifestyle factors and relevant anthropometric characteristics play a role in lymphoma etiology.

Genetic susceptibility studies of lymphoma may serve to identify at risk populations and clarify important disease mechanisms. This review considered all studies published through October 2006 on the contribution of genetic polymorphisms in the risk of lymphoma. Numerous studies implicate the role of genetic variants that promote B-cell survival and growth with increased risk of lymphoma. Several reports including a large pooled study by InterLymph, an international consortium of non-Hodgkin lymphoma (NHL) case-control studies, found positive associations between variant alleles in TNF -308G>A and IL10 -3575T>A genes and risk of diffuse large B-cell lymphoma. Four studies reported positive associations between a GSTT1 deletion and risk of Hodgkin and non-Hodgkin lymphoma. Genetic studies of folate-metabolizing genes implicate folate in NHL risk, but further studies that include folate and alcohol intakes are needed. Links between NHL and genes involved in energy regulation and hormone production and metabolism may provide insights into novel mechanisms implicating neuro- and endocrine-immune cross-talk with lymphomagenesis. However, this links will need replication in larger populations. Numerous studies suggest that common genetic variants with low penetrance influence lymphoma risk, though replication studies will be needed to eliminate false positive associations.

Objective Appendectomy remains one of the most common surgical procedures, but possible long-term consequences for health and disease are incompletely investigated. The appendix forms part of the secondary lymphoid system and appendectomy has been associated with increased risks of hematolymphoproliferative malignancies in some studies. Materials and methods We examined the risk of lymphoid neoplasms in a large cohort of 337,437 appendectomised patients <60 years of age in Sweden 1975–2009. We estimated relative risks of non-Hodgkin lymphoma (NHL) and major subtypes, Hodgkin lymphoma (HL), chronic lymphocytic leukaemia (CLL), myeloma, and acute lymphoblastic leukaemia (ALL) versus the general population using standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). Results There was no increased risk of NHL (SIR = 0.97, 95%CI 0.88–1.06), major NHL subtypes, CLL (SIR = 0.87, 95%CI 0.70–1.06), myeloma (SIR = 1.14, 95%CI 0.96–1.33) or ALL (SIR = 1.10, 95%CI 0.80–1.47) following appendectomy. An increased risk of HL was observed among patients diagnosed with appendicitis (SIR = 1.29, 95%CI 1.07–1.54, p=0.007), especially individuals aged <20 years at surgery (SIR = 1.43, 95%CI 1.11–1.82), and for the nodular sclerosis subtype of HL (SIR = 1.55, 95%CI 1.01–2.27). A marginally increased risk of myeloma was noted among men, but the association was limited to the first few years of follow-up. Conclusion Appendectomy is not associated with any notable increase in risk of lymphoid neoplasms. A small increased risk of HL following appendicitis (rather than appendectomy per se) could reflect a true association, or shared susceptibility to infection/inflammation among individuals prone to develop HL. The association observed for myeloma may be explained by chance or surveillance bias.

Historical review of lymphomas.

Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are associated with increased risks of lymphomas in the non-HIV setting. Their impacts on HIV-associated lymphomas deserved further studies in the modern combined antiretroviral therapy (cART) era. We evaluated the associations between HCV, HBV and HIV-related lymphomas in the Lymphovir-ANRS-CO16 cohort. Prevalence of HCV seropositivity and chronic HBV infections were compared with those observed in the French Hospital Database on HIV (FHDH-ANRS-CO4). Between 2008 and 2015, 179 patients with HIV-related lymphomas from 32 French hospitals were enrolled, 69 had Hodgkin's lymphoma (39%), and 110 non-Hodgkin's lymphoma (NHL) (61%). The prevalence of HCV infection was higher in patients with NHL than in the FHDH-ANRS-CO4 [26 versus 14%, odd ratio (OR): 2.15; 95% confidence interval (1.35-3.32)] whereas there was no association between Hodgkin's lymphoma and chronic HCV infection. Chronic HBV infection was not associated with NHL in our cohort with a prevalence of 5 versus 7% in FHDH-ANRS-CO4 but tended to be associated with Hodgkin's lymphoma [prevalence of 14%, OR: 2.16 (0.98-4.27)]. Chronic HCV infection tended to pejoratively impact 2-year overall survival in patients with NHL: 72% [57%, 91%] versus 82% [74%, 91%], hazard ratio: 2.14 [0.95-4.84]. In contrast, chronic HBV infection did not correlate with outcome. In the modern cART era, chronic HCV infection is associated with an increased risk of NHL in PLWHIV and tends to pejoratively impact overall survival. HBV infection is not associated with the risk of NHL but with a borderline increase of Hodgkin's lymphoma risk.