Personal sun exposure and risk of non Hodgkin lymphoma: a pooled analysis from the Interlymph Consortium

In 2004-2007 4 independent case-control studies reported evidence that sun exposure might protect against NHL; a fifth, in women only, found increased risks of NHL associated with a range of sun exposure measurements. These 5 studies are the first to examine the association between personal sun exposure and NHL. We report here on the relationship between sun exposure and NHL in a pooled analysis of 10 studies participating in the International Lymphoma Epidemiology Consortium (InterLymph), including the 5 published studies. Ten case-control studies covering 8,243 cases and 9,697 controls in the USA, Europe and Australia contributed original data for participants of European origin to the pooled analysis. Four kinds of measures of self-reported personal sun exposure were assessed at interview. A two-stage estimation method was used in which study-specific odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounders including smoking and alcohol use, were obtained from unconditional logistic regression models and combined in random-effects models to obtain the pooled estimates. Risk of NHL fell significantly with the composite measure of increasing recreational sun exposure, pooled OR = 0.76 (95% CI 0.63-0.91) for the highest exposure category (p for trend 0.01). A downtrend in risk with increasing total sun exposure was not statistically significant. The protective effect of recreational sun exposure was statistically significant at 18-40 years of age and in the 10 years before diagnosis, and for B cell, but not T cell, lymphomas. Increased recreational sun exposure may protect against NHL.     

Self-reported history of infections and the risk of non-Hodgkin lymphoma: An InterLymph pooled analysis

We performed a pooled analysis of data on self-reported history of infections in relation to the risk of non-Hodgkin lymphoma (NHL) from 17 case-control studies that included 12,585 cases and 15,416 controls aged 16-96 years at recruitment. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were estimated in two-stage random-effect or joint fixed-effect models, adjusting for age, sex and study centre. Data from the 2 years before diagnosis (or date of interview for controls) were excluded. A self-reported history of infectious mononucleosis was associated with an excess risk of NHL (OR = 1.26, 95% CI = 1.01-1.57 based on data from 16 studies); study-specific results indicate significant (I(2) = 51%, p = 0.01) heterogeneity. A self-reported history of measles or whooping cough was associated with an approximate 15% reduction in risk. History of other infection was not associated with NHL. We find little clear evidence of an association between NHL risk and infection although the limitations of data based on self-reported medical history (particularly of childhood illness reported by older people) are well recognized.     

Association between obesity and the risk of malignant lymphoma in Japanese: a case–control study

Although marked differences in anthropometric characteristics and malignant lymphoma (ML) incidence suggest that the association between obesity and ML risk in Asian and non‐Asian populations may differ, few studies have investigated this association in Asian populations. Here, we conducted a sex‐ and age‐matched case–control study in a Japanese population using 782 cases and 3,910 noncancer controls in the hospital‐based Epidemiological Research Program at Aichi Cancer Center Hospital. Odds ratios (ORs) and 95% confidence intervals (CIs) for anthropometric characteristics were estimated using a conditional logistic regression model that incorporated smoking and alcohol intake. Recent body weight and body mass index (BMI) showed marginally significant association with ML risk (ORs [95% CIs] per 5‐unit increase in recent weight and BMI; 1.04 [0.99–1.09] and 1.11 [0.98–1.27], respectively). On the other hand, weight and BMI in early adulthood exhibited a strong association with ML risk (ORs [95% CIs] per 5‐unit increase in early adulthood weight and BMI; 1.11 [1.05–1.18] and 1.33 [1.13–1.55], respectively). Further, in women, a BMI of 25.0–29.9 kg/m², defined as obesity in Asian populations, during early adulthood was significantly associated with ML risk compared to the normal range of 18.5–22.9 kg/m². By histological ML subtype, the point estimates of ORs for obesity relative to normal weight in early adulthood were over unity for non‐Hodgkin lymphoma (NHL) as a whole and significant for diffuse large B‐cell lymphoma (DLBCL). In conclusion, our study in Japanese subjects suggested that early adulthood obesity is associated with the risk of NHL, particularly DLBCL.     

Non-Hodgkin lymphoma of the breast

BACKGROUND: Primary lymphoma of the breast has been reported to have a high local and central nervous system recurrence (CNS) rate, suggesting the need for consolidation radiotherapy and CNS prophylaxis. A retrospective study was done to evaluate the institutional experience in this patient population. METHODS: In all, 37 patients with lymphoma involving the breast at initial diagnosis and managed at Stanford University from 1981-2005 were included. Diagnostic tissue biopsies were obtained either from the breast mass or an involved lymph node. Treatment and response data, patterns of recurrence, and outcomes were reviewed. RESULTS: Diffuse large B cell lymphoma (DLBCL) was the most common histologic subtype seen in 18 of 37 (49%) patients. Follicular and marginal zone subtypes were seen in 38%. Most patients presented with an incidental breast mass in stage I(E) or II(E). Four (11%) patients presented with bilateral breast involvement, with only 1 patient presenting with CNS disease. DLBCL patients received doxorubicin-based chemotherapy, with 70% receiving involved field radiotherapy and a single patient receiving intrathecal therapy. No recurrences occurred in the involved breast and a single parenchymal CNS recurrence was recorded. Among the DLBCL patients, the 5-year progression-free survival (PFS) was 61%, with a median follow-up of 3.8 years (range, 5 months to 19 years) and the 5-year overall survival (OS) was estimated at 82%. Patients with indolent lymphoma had an estimated 5-year PFS of 76% and an OS of 92%. CONCLUSIONS: DLBCL of the breast was successfully treated with doxorubicin-based chemotherapy alone or with involved field radiotherapy in an estimated 61% of patients at 5 years. A single CNS recurrence was observed in our series of patients, most of whom presented with limited disease.     

Anthropometric factors and risk of melanoma in women: a pooled analysis

Anthropometric factors such as height, weight and body mass index are related to the occurrence of certain malignancies in women including cancers of the breast, ovary and endometrium. Several studies have investigated the relation between height and weight or body mass and the risk of cutaneous melanoma in women, but results have been inconsistent. We conducted a collaborative analysis of these factors using the original data from 8 case-control studies of melanoma in women (2,083 cases and 2,782 controls), with assessment of the potential confounding effects of socioeconomic, pigmentary and sun exposure-related factors. Women in the highest quartile of height had an increased risk of melanoma [pooled odds ratio (pOR) 1.3, 95% confidence interval (CI) 1.1-1.6]. We also found an elevated risk associated with weight gain in adult life of 2 kg or more (pOR 1.5, 95% CI 1.1-2.0). Stratifying by age at melanoma diagnosis (<50, >or=50 yr), we found this risk greater among women <50 yr of age. Associations were unaffected by adjustment for other known risk factors for melanoma. There was no evidence that the effects varied for different histologic subtypes of cutaneous melanoma. There was no association with body weight per se, body mass index, or body surface area, either recent or in young adulthood. In aggregate, data from these studies suggest that greater height and weight gain may be risk factors for cutaneous melanoma in women.     

Smoking,alcohol use,obesity, and overall survival from non‐Hodgkin lymphoma

BACKGROUND:

Smoking, alcohol use, and obesity appear to increase the risk of developing non‐Hodgkin lymphoma (NHL), but to the authors' knowledge, few studies to date have assessed their impact on NHL prognosis.

METHODS:

The association between prediagnosis cigarette smoking, alcohol use, and body mass index (BMI) and overall survival was evaluated in 1286 patients enrolled through population‐based registries in the United States from 1998 through 2000. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox regression, adjusting for clinical and demographic factors.

RESULTS:

Through 2007, 442 patients had died (34%), and the median follow‐up for surviving patients was 7.7 years. Compared with never smokers, former (HR, 1.59; 95% CI, 1.12‐2.26) and current (HR, 1.50; 95% CI, 0.97‐2.29) smokers had poorer survival, and poorer survival was found to be positively associated with smoking duration, number of cigarettes smoked per day, pack‐years of smoking, and shorter time since quitting (all P <0.01). Alcohol use was associated with poorer survival (P = 0.03); compared with nonusers. Those drinking >43.1 g/week (median intake among drinkers) had poorer survival (HR, 1.55; 95% CI, 1.06‐2.27), whereas those drinkers consuming less than this amount demonstrated no survival disadvantage (HR, 1.13; 95% CI, 0.75‐1.71). Greater BMI was associated with poorer survival (P = 0.046), but the survival disadvantage was only noted among obese individuals (HR, 1.32 for BMI ≥30 vs BMI 20‐24.9; 95% CI, 1.02‐1.70). These results held for lymphoma‐specific survival and were broadly similar for diffuse large B‐cell lymphoma and follicular lymphoma.

CONCLUSIONS:

NHL patients who smoked, consumed alcohol, or were obese before diagnosis were found to have a poorer overall and lymphoma‐specific survival. Cancer 2010. © 2010 American Cancer Society.     

Maternal smoking during pregnancy and childhood lymphoma: a meta-analysis

Results from epidemiological studies exploring the association between childhood lymphoma and maternal smoking during pregnancy have been contradictory. This meta-analysis included all published cohort (n = 2) and case-control (n = 10) articles; among the latter, the data of the Greek Nationwide Registry for Childhood Hematological Malignancies study were updated to include all recently available cases (-2008). Odds ratios (ORs), relative risks and hazard ratios were appropriately pooled in three separate analyses concerning non-Hodgkin lymphoma (NHL, n = 1,072 cases), Hodgkin lymphoma (HL, n = 538 cases) and any lymphoma (n = 1,591 cases), according to data availability in the included studies. An additional metaregression analysis was conducted to explore dose-response relationships. A statistically significant association between maternal smoking (any vs. no) during pregnancy and risk for childhood NHL was observed (OR = 1.22, 95% confidence interval, CI: 1.03-1.45, fixed effects model), whereas the risk for childhood HL was not statistically significant (OR = 0.90, 95% CI: 0.66-1.21, fixed effects model). The analysis on any lymphoma did not reach statistical significance (OR = 1.10, 95% CI = 0.96-1.27, fixed effects model), possibly because of the case-mix of NHL to HL. No dose-response association was revealed in the metaregression analysis. In conclusion, this meta-analysis points to a modest increase in the risk for childhood NHL, but not HL, among children born by mothers smoking during pregnancy. Further investigation of dose-response phenomena in the NHL association, however, warrants accumulation of additional data.     

Liver cancer and non-Hodgkin lymphoma in hepatitis C virus-infected patients: results from the DANVIR cohort study

Hepatitis C virus (HCV)-infection can cause hepatocellular carcinoma (HCC) and most likely non-Hodgkin lymphoma (NHL). No studies have compared the risk of these cancers between patients with chronic and cleared HCV-infection. The aim of this study was to estimate the 10-year risk of HCC and NHL in HCV-infected patients and to compare the risk of these cancers between HCV-infected patients and the general population in Denmark and between patients with chronic and cleared HCV-infection. Nationwide cohorts were used: 11,975 HCV-infected patients in the DANVIR cohort and 71,850 individuals from an age- and gender-matched general population cohort. Within DANVIR, 4,158 patients with chronic HCV-infection and 2,427 patients with cleared HCV-infection were studied. The 10-year risks of HCC and NHL in HCV-infected patients were 1.0% [95% confidence interval (CI): 0.8-1.3%] and 0.1% (95% CI: 0.1-0.2%), respectively. Compared to the general population, HCV-infected patients had a 62.91-fold increased risk of HCC (95% CI: 28.99-136.52), a 29.97-fold increased risk of NHL during the first year of follow-up (95% CI: 6.08-147.84), and a 1.26-fold increased risk of NHL after the first year (95% CI: 0.36-4.41). Chronic HCV-infection was associated with a 4.71-fold increased risk of HCC (95% CI: 1.67-13.32) compared to cleared HCV-infection; 5 and 0 events of NHL occurred in patients with chronic and cleared HCV-infection, respectively. HCC-risk is increased substantially in HCV-infected patients compared to the general population. Chronic as opposed to cleared HCV-infection increases the risk of HCC and perhaps NHL.     

Primary cardiac lymphoma: an analysis of presentation, treatment, and outcome patterns

BACKGROUND:

Primary cardiac lymphoma (PCL) represents a rare subset of non‐Hodgkin lymphoma, characterized by poor outcomes. The authors aimed to construct a framework of known clinical presentations, diagnostic features, disease complications, treatment, and outcomes to improve prognostication.

METHODS:

Individual patient data were obtained from defined cases of PCL (1949‐2009) and systematically analyzed.

RESULTS:

The authors report results of a review of 197 cases of PCL, with half of all cases reported since 1995. Survival was affected by 4 factors: immune status, left ventricular involvement, presence of extra‐cardiac disease, and arrhythmia. Median overall survival (OS) for immunocompromised and immunocompetent was 3.5 months (m) and not reached, respectively (HR 0.29, 95% CI, 0.13‐0.68; P = .004). LV involvement was uncommon (26%) and associated with an OS of only 1m, whereas patients free of LV involvement had a median OS of 22m (HR 0.28, 95% CI, 0.12‐0.64; P = .002). Patients with extracardiac disease had shorter median OS compared with those without (6m vs 22m, HR 0.49, 95% CI, 0.26‐0.91; P = .02). Those patients with an arrhythmia of any type had a median OS that was not reached (n = 55), whereas those without rhythm disturbances (n = 41) had median OS of 6m (HR 0.51, 95% CI, 0.29‐0.91; P = .024). Overall response rate to therapy was 84%, with long‐term OS over 40%.

CONCLUSIONS:

The current study presents the largest analysis of PCL to date. The data demonstrate that PCL is now more frequently diagnosed premortem and appears to have reasonable response rates. Lack of LV involvement and the presence of arrhythmias are associated with improved survival. Cancer 2011. © 2010 American Cancer Society.     

Pegfilgrastim primary prophylaxis in patients with non-Hodgkin lymphoma: results from an integrated analysis

Severe neutropenia and febrile neutropenia (FN) are serious, dose‐limiting side effects of chemotherapy for aggressive non‐Hodgkin lymphoma (NHL). Observational data suggest that with current practice neutropenia management up to 23% of patients receiving CHOP‐like regimens experience FN, and around half of patients do not receive the planned relative dose intensity (RDI). In this integrated analysis we assessed the efficacy of pegfilgrastim for preventing FN and related outcomes in patients with NHL. A literature search was used to identify chemotherapy regimens with an FN risk ≥15% that are used to treat lymphoma. Search results were then used to identify clinical trials in which these regimens were administered with pegfilgrastim primary prophylaxis. Individual patient data were available for three trials meeting the inclusion criteria, and these were combined in an integrated analysis. The primary outcome measure was the incidence of FN in any cycle. A total of 282 patients were included in the analysis [mean age 65 years (SD ± 12.5 years); 172 (61%) aged ≥ 65 years]. All patients had NHL and 244 (87%) received RCHOP‐21. The incidence of FN in any cycle was 16% (95% CI 12–20%) (13% in patients aged <65 years; 18% in patients aged ≥65 years). Chemotherapy dose delays >3 days occurred in 26% (95% CI 20–31%) of patients, and was relatively consistent across age groups. Chemotherapy dose reductions ≥10% were seen in 43% (95% CI 37–49%) of patients and were more frequent in the elderly. Overall, 83% (95% CI 78–87%) of patients received ≥90% RDI (89% of patients aged <65 years; 78% of patients aged ≥65 years). In this integrated analysis of NHL patients at higher risk of FN receiving pegfilgrastim primary prophylaxis, the overall incidence of FN was 16% and a high proportion of both younger and elderly patients achieved RDI ≥90%. Copyright © 2011 John Wiley & Sons, Ltd.     

Non-Hodgkin's lymphoma, obesity and energy homeostasis polymorphisms

A population-based case-control study of lymphomas in England collected height and weight details from 699 non-Hodgkin's lymphoma (NHL) cases and 914 controls. Obesity, defined as a body mass index (BMI) over 30 kg m(-2) at five years before diagnosis,, was associated with an increased risk of NHL (OR = 1.5, 95% CI 1.1-2.1). The excess was most pronounced for diffuse large B-cell lymphoma (OR = 1.9, 95% CI 1.3-2.8). Genetic variants in the leptin (LEP 19G > A, LEP -2548G > A) and leptin receptor genes (LEPR 223Q > R), previously shown to modulate NHL risk, as well as a polymorphism in the energy regulatory gene adiponectin (APM1 276G>T), were investigated. Findings varied with leptin genotype, the risks being decreased with LEP 19AA (OR = 0.7, 95% CI 0.5-1.0) and increased with LEP -2548GA (OR = 1.3, 95% CI 1.0-1.7) and -2548AA (OR = 1.4, 95% CI 1.0-1.9), particularly for follicular lymphoma. These genetic findings, which were independent of BMI, were stronger for men than women.     

Non‐Hodgkin lymphoma in Romania: a single‐centre experience

Epidemiologic studies of non‐Hodgkin lymphoma (NHL) in Eastern Europe are scarce in the literature. We report the experience of the “Ion Chiricuta” Institute of Oncology in Cluj‐Napoca (IOCN), Romania, in the diagnosis and outcome of patients with NHL. We studied 184 consecutive NHL patients diagnosed in the Pathology Department of IOCN during the years 2004–2006. We also obtained epidemiological data from the Northwestern (NW) Cancer Registry. In the IOCN series, the most common lymphoma subtype was diffuse large B‐cell lymphoma (43.5%), followed by the chronic lymphocytic leukaemia/small lymphocytic lymphoma (21.2%). T‐cell lymphomas represented a small proportion (8.2%). The median age of the patients was 57 years, with a male‐to‐female ratio of 0.94. Patients with indolent B‐cell lymphomas had the best overall survival, whereas those with mantle cell lymphoma had the worst survival. The NW Cancer Registry data showed that the occurrence of NHL in the NW region of Romania was higher in men [world age‐standardized incidence rate/100 000 (ASR)—5.9; 95% CI 5.1–6.6] than in women (ASR—4.1; 95% CI 3.5–4.7) with age‐standardized male‐to‐female ratio of 1.44 (p = 0.038). Chronic lymphocytic leukaemia/small lymphocytic lymphoma was the most common NHL in the NW region of Romania, accounting for 43% of all cases, followed by diffuse large B‐cell lymphoma (36%). The 5‐year, age‐standardized cumulative relative survival for NHL in the County of Cluj in NW Romania, for the period of 2006–2010, was 51.4%, with 58.4% survival for men and 43.2% for women. Additional studies of NHL in Eastern Europe are needed. Copyright © 2015 John Wiley & Sons, Ltd.     

Early life risk factors in cancer: the relation of birth weight to adult obesity

The intrauterine environment appears to play a role in the development of adult diseases, including several prominent cancers. Our study aims to characterize the relationship between birth weight, a measure of the intrauterine environment, and adult obesity. A population-based sample of women aged 50-79, living in the states of Massachusetts, New Hampshire or Wisconsin, were randomly selected from lists of licensed drivers and Medicare beneficiaries to participate as controls in a case-control study of breast cancer. Information on birth weight, adult height and adult weight were collected through structured telephone interviews from 1992-1995. Our analysis was based on 1,850 interviews. A U-shaped relationship between birth weight and adult BMI was observed. Median adult BMI for the birth weight categories (in kilograms) <2.3, 2.3<2.5, 2.5<3.2, 3.2<3.9, 3.9<4.5 and > or =4.5 were 26.6, 24.4, 25.1, 25.5, 25.4 and 26.6 kg/m respectively. Compared to women 2.5<3.2 kg at birth, women in highest birth weight category (> or =4.5 kg) had an odds ratio of 1.99 (95% CI 1.13-3.48) of being obese (> or =30 kg/m(2)) as adults. The odds ratio for women in the <2.3 kg birth weight category was 1.67 (95% CI 1.01-2.76). These data suggest that both low and high birth weights are associated with higher adult BMI and support the hypothesis that fetal experience may influence adult obesity with potential consequences for risk of several major cancers.     

GBV‐C/hepatitis G virus infection and non‐Hodgkin lymphoma: a case control study

We investigated whether there was an association between GBV‐C viremia and the development of non‐Hodgkin lymphoma (NHL) in 553 NHL cases and 438 controls from British Columbia, Canada. Cases were aged 20–79, diagnosed between March 2000 and February 2004, and resident in Greater Vancouver or Victoria. Cases and controls were tested for GBV‐C RNA by RT‐PCR and positive samples were genotyped. Overall, GBV‐C RNA was detected in 4.5% of NHL cases vs. 1.8% of controls [adjusted odds ratio (OR) = 2.72, 95% confidence interval (CI) = 1.22–6.69]. The association between GBV‐C RNA detection and NHL remained even after individuals with a history of prior transfusion, injection drug use and hepatitis C virus sero‐positivity were excluded. GBV‐C viremia showed the strongest association with diffuse large B cell lymphoma (adjusted OR = 5.18, 95% CI = 2.06–13.71). Genotyping was performed on 29/33 GBV‐C RNA positive individuals; genotypes 2a (n = 22); 2b (n = 5) and 3 (n = 2) were identified, consistent with the distribution of genotypes found in North America. This is the largest case‐control study to date associating GBV‐C viremia and NHL risk. As GBV‐C is known to be transmitted through blood products this may have important implications for blood safety.     

A multicenter phase 2 study of risk-adjusted salvage chemotherapy incorporating vinorelbine and gemcitabine for relapsed and refractory lymphoma

BACKGROUND.

Administration of salvage chemotherapy to patients with relapsed or refractory lymphoma is associated with significant toxicity. Vinorelbine and gemcitabine are novel chemotherapeutic agents with minimal overlapping toxicity. We present a phase 2 study of vinorelbine and gemcitabine with or without ifosfamide administered in an ambulatory care setting for relapsed or refractory lymphoma.

METHODS.

Ninety patients were enrolled. Group 1 comprised patients with “good” risk disease, Group 2 comprised patients with “high” risk disease, and Group 3 comprised patients relapsing after prior stem cell transplant. Patients in Group 1 and Group 3 received vinorelbine and gemcitabine with filgrastim support (VGF); those in Group 2 received the above regimen with ifosfamide (FGIV). We incorporated a standardized interim evaluation with dose escalation for patients with suboptimal response after 2 cycles.

RESULTS.

Toxicities were acceptable. Febrile neutropenia was uncommon: 7% after VGF (7 of 107 cycles) and 19% for FGIV (26 of 148 cycles). Unplanned admissions occurred in 23 of 107 cycles (21%) after VGF and 50 of 148 (34%) after FGIV. Overall response for Groups 1, 2 and 3, respectively was 76%, 39% and 50%, with median overall survival of 28, 9 and 30 months.

CONCLUSIONS.

Vinorelbine‐based and gemcitabine‐based chemotherapy is effective in the salvage setting against lymphoma and can be administered in an ambulatory setting. Cancer 2008. © 2008 American Cancer Society.     

Periodontal disease and risk of non‐Hodgkin lymphoma in the Health Professionals Follow‐Up Study

Periodontal disease is a chronic inflammatory condition that has been associated with chronic diseases, including cancer. In an earlier prospective cohort analysis within the Health Professionals Follow‐Up Study (HPFS), we observed a 31% higher risk of non‐Hodgkin lymphoma (NHL) among participants with severe periodontal disease at baseline. Here, we extend the study with an additional 8 years of follow‐up, and conduct analyses with updated periodontal disease status and NHL subtypes. The HPFS is an ongoing prospective cohort study of 51,529 men in the USA Between baseline in 1986 and 2012, 875 cases of NHL were diagnosed, including 290 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 85 diffuse large B‐cell lymphomas and 91 follicular lymphomas. We performed multivariable Cox proportional hazards regression to evaluate associations of interest. History of periodontal disease at baseline was positively associated with risk of NHL overall (hazard ratio (HR) = 1.26, 95% confidence interval (CI): 1.06–1.49) and CLL/SLL (HR = 1.41, 95% CI: 1.04–1.90). With updated periodontal status, HRs were 1.30 (95% CI: 1.11–1.51) for NHL overall and 1.41 (95% CI: 1.08–1.84) for CLL/SLL. In contrast, after adjusting for periodontal disease, tooth loss was inversely associated with NHL, suggesting that other causes or consequences of tooth loss may have different implications for NHL etiology. Our findings suggest that periodontal disease is a risk factor for NHL. Whether periodontal disease is a direct or indirect cause of NHL, or is a marker of underlying systemic inflammation and/or immune dysregulation, warrants further investigation.     

Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph)

BackgroundThe etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes.Patients and methodsThrough the InterLymph Consortium, 12 case–control studies regarding cigarette smoking and HL were identified. Pooled analyses on the association between smoking and HL stratified by tumor histology and Epstein–Barr virus (EBV) status were conducted using random effects models adjusted for confounders. Analyses included 3335 HL cases and 14 278 controls.ResultsOverall, 54.5% of cases and 57.4% of controls were ever cigarette smokers. Compared with never smokers, ever smokers had an odds ratio (OR) of HL of 1.10 [95% confidence interval (CI) 1.01–1.21]. This increased risk reflected associations with mixed cellularity cHL (OR = 1.60, 95% CI 1.29–1.99) and EBV-positive cHL (OR = 1.81, 95% CI 1.27–2.56) among current smokers, whereas risk of nodular sclerosis (OR = 1.09, 95% CI 0.90–1.32) and EBV-negative HL (OR = 1.02, 95% CI 0.72–1.44) was not increased.ConclusionThese results support the notion of etiologic heterogeneity between HL subtypes, highlighting the need for HL stratification in future studies. Even if not relevant to all subtypes, our study emphasizes that cigarette smoking should be added to the few modifiable HL risk factors identified.     

Physical activity and the risk of non-Hodgkin lymphoma subtypes: A pooled analysis

Non-Hodgkin lymphoma (NHL) is composed of a heterogeneous collection of subtypes with considerable differences in genetics, biology and aetiology. Studies to date on physical activity and NHL risk have not had sufficient sample size to evaluate whether associations differ by subtype. We pooled data from nine case-control studies to examine the association between moderate-to-vigorous intensity physical activity (MVPA) and risk of NHL overall and by subtype (diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukaemia/small lymphocytic lymphoma, marginal zone lymphoma and mature T-cell lymphoma). A total of 5653 cases and 9115 controls were included in the pooled analysis. Physical activity was harmonised across nine studies and modelled as study-specific tertiles. Multinomial logistic regression was used to estimate the association between physical activity and NHL, adjusting for confounders. The overall odds of NHL was 13% lower among participants in the most active tertile of MVPA compared to the least active tertile (adjusted odds ratio = 0.87, 95% CI = 0.80, 0.95). Similar decreases were observed across NHL subtypes. In summary, in this pooled analysis of case-control studies, physical activity was associated with a modest risk reduction for each NHL subtype examined and with overall NHL.