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.

Associations between frailty and cancer-specific mortality among older women with breast cancer.

PURPOSE: Frailty is assessed when making treatment decisions among older women with breast cancer (BC), which in turn impacts survival. We evaluated associations between pre-diagnosis frailty and risks of BC-specific and all-cause mortality in older women. METHODS: We conducted a retrospective cohort study of Medicare beneficiaries ages ≥ 65 years with stage I-III BC using the Surveillance, Epidemiology and End Results-Medicare Health Outcome Survey Data Resource. Frailty was measured using the deficit-accumulation frailty index, categorized as robust, pre-frail, or frail, at baseline and during follow-up. Fine and Gray competing risk and Cox proportional hazards models were used to estimate subdistribution hazard ratios (SHR) and hazard ratios (HR) with 95% confidence intervals (CI) for BC-specific and all-cause mortality, respectively. RESULTS: Among 2411 women with a median age of 75 years at BC diagnosis, 49.5% were categorized as robust, 29.4% were pre-frail and 21.1% were frail. Fewer frail women compared to robust women received breast-conserving surgery (52.8% vs. 61.5%, frail vs. robust, respectively) and radiation (43.5% vs. 51.8%). In multivariable analyses, degree of frailty was not associated with BC-specific mortality (frail vs robust SHR 1.47, 95% CI 0.97-2.24). However, frail women with BC had higher risks of all-cause mortality compared to robust women with BC (HR 2.32, 95% CI 1.84-2.92). CONCLUSION: Among a cohort of older women with BC, higher degrees of frailty were associated with higher risk of all-cause mortality, but not BC-specific mortality. Future study should examine if preventing progression of frailty may improve all-cause mortality.

Targets of biologic disease-modifying antirheumatic drugs and risk of multiple myeloma.

Several commonly used immune-suppressing biologic drugs target proteins and cytokines involved in myeloma pathogenesis. Our objective was to determine whether targeted biologic disease-modifying antirheumatic drugs (DMARDs) are associated with risk of multiple myeloma (MM). We conducted a nested case-control study within a retrospective cohort of 56,886 commercially insured adults undergoing treatment for rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis between 2009 and 2015 using the Truven Health MarketScan Databases. MM cases (n = 287) were matched to up to 10 controls (n = 2,760) on age, sex and rheumatologic indication using incidence density sampling without replacement. Our exposures of interest were biologic DMARDs targeting tumor necrosis factor-alpha, interleukin 6, cytotoxic t-lymphocyte-associated protein-4 and depletion of B cells. Relative risks were estimated as adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression models. Cases and controls were similar with respect to use of prescription NSAIDs and concurrent conventional-synthetic DMARDs. Cases had slightly fewer etanercept users (4% vs. 7%) and slightly more tocilizumab users (1.4% vs. 0.4%). Compared to patients treated with only conventional-synthetic DMARDs, those receiving concomitant conventional-synthetic plus biologic DMARDs had lower risk of developing MM (OR = 0.48; 95% CI 0.30-0.88; p = 0.02). Risks differed by drug target with an inverse association observed with use of etanercept inhibiting tumor necrosis factor-alpha (OR = 0.55; 95% CI 0.30-1.02; p = 0.06) and a positive association with tocilizumab inhibiting interleukin-6 (OR = 4.33; 95% CI 1.33-14.19; p = 0.02) compared to biologic DMARD-naïve patients. Further investigation is warranted to understand the roles of drugs suppressing tumor necrosis factor-alpha and interleukin-6 in myeloma pathogenesis.

Self-reported health and survival in older patients diagnosed with multiple myeloma.

PURPOSE: Patient-reported outcomes such as self-reported health (SRH) are important in understanding quality cancer care, yet little is known about links between SRH and outcomes in older patients with multiple myeloma (MM). We evaluated associations between SRH and mortality among older patients with MM. METHODS: We analyzed a retrospective cohort of patients ages ≥ 65 years diagnosed with first primary MM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) data resource. Pre-diagnosis SRH was grouped as high (excellent/very good/good) or low (fair/poor). We used Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between SRH and all-cause and MM-specific mortality. RESULTS: Of 521 MM patients with mean (SD) age at diagnosis of 76.8 (6.1) years, 32% reported low SRH. In multivariable analyses, low SRH was suggestive of modest increased risks of all-cause mortality (HR 1.32, 95% CI 1.02-1.71) and MM-specific mortality (HR 1.22, 95% CI 0.87-1.70) compared to high SRH. CONCLUSION: Findings suggest that low pre-diagnosis SRH is highly prevalent among older patients with MM and is associated with modestly increased all-cause mortality. Additional research is needed to address quality of life and modifiable factors that may accompany poor SRH in older patients with MM.

Depressive symptoms, mental health-related quality of life, and survival among older patients with multiple myeloma.

PURPOSE: To examine the impact of pre-diagnosis depressive symptoms and mental health-related quality of life (HRQOL) on survival among older patients with multiple myeloma (MM). METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data resource. Patients aged 65 years and older diagnosed with first primary MM between 1998 and 2014 were identified, and presence of depressive symptoms was determined based on responses to 3 depression screening questions prior to MM diagnosis. Veterans RAND 12 mental component summary (MCS) scores were analyzed to evaluate mental HRQOL. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for risks of all-cause and cancer-specific mortality. RESULTS: Of 522 patients, mean (SD) age at diagnosis was 76.9 (6.1) years and 158 (30%) reported depressive symptoms. Patients with depressive symptoms had a higher number of comorbid conditions and nearly all (84%) scored below the median MCS. Pre-diagnosis depressive symptoms were not associated with all-cause (HR = 1.01, 95% CI 0.79-1.29) or cancer-specific mortality (HR = 0.94, 95% CI 0.69-1.28). MM patients scoring in the second MCS tertile (vs the highest tertile) had a modestly increased risk of all-cause (HR = 1.19, 95% CI 0.91-1.55) and cancer-specific mortality (HR = 1.17, 95% CI 0.86-1.60), but these estimates were not statistically significant. CONCLUSION: Pre-diagnosis depressive symptoms and lower mental HRQoL did not impact survival among older MM patients. Highly prevalent depressive symptoms among older MM patients deserve clinical attention. Such efforts can inform clinicians in tailoring care for this vulnerable population.

Genome-wide mapping of 5-hydroxymethylcytosines in circulating cell-free DNA as a non-invasive approach for early detection of hepatocellular carcinoma.

OBJECTIVE: The lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC). We sought to develop a non-invasive diagnostic approach using circulating cell-free DNA (cfDNA) for the early detection of HCC. DESIGN: Applying the 5hmC-Seal technique, we obtained genome-wide 5-hydroxymethylcytosines (5hmC) in cfDNA samples from 2554 Chinese subjects: 1204 patients with HCC, 392 patients with chronic hepatitis B virus infection (CHB) or liver cirrhosis (LC) and 958 healthy individuals and patients with benign liver lesions. A diagnostic model for early HCC was developed through case-control analyses using the elastic net regularisation for feature selection. RESULTS: The 5hmC-Seal data from patients with HCC showed a genome-wide distribution enriched with liver-derived enhancer marks. We developed a 32-gene diagnostic model that accurately distinguished early HCC (stage 0/A) based on the Barcelona Clinic Liver Cancer staging system from non-HCC (validation set: area under curve (AUC)=88.4%; (95% CI 85.8% to 91.1%)), showing superior performance over α-fetoprotein (AFP). Besides detecting patients with early stage or small tumours (eg, ≤2.0 cm) from non-HCC, the 5hmC model showed high capacity for distinguishing early HCC from high risk subjects with CHB or LC history (validation set: AUC=84.6%; (95% CI 80.6% to 88.7%)), also significantly outperforming AFP. Furthermore, the 5hmC diagnostic model appeared to be independent from potential confounders (eg, smoking/alcohol intake history). CONCLUSION: We have developed and validated a non-invasive approach with clinical application potential for the early detection of HCC that are still surgically resectable in high risk individuals.

Myelodysplastic syndrome and acute myeloid leukemia after receipt of granulocyte colony-stimulating factors in older patients with non-Hodgkin lymphoma.

BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs), which are used for the prevention of complications from chemotherapy-related neutropenia, are linked to the risk of developing second primary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The objective of this study was to examine the correlation between using a specific G-CSF agent and the risk of MDS/AML among older patients with non-Hodgkin lymphoma (NHL). METHODS: This was a retrospective cohort study of adults aged >65 years who were diagnosed with first primary NHL between 2001 and 2011. With data from the Surveillance, Epidemiology, and End Results-Medicare-linked database, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the risk of MDS/AML associated with the receipt of G-CSF(filgrastim and pegfilgrastim) in Cox proportional-hazards models, which were stratified according to treatment accounting for confounding by indication. RESULTS: Among 18,245 patients with NHL patients who had a median follow-up of 3.5 years, 56% received chemotherapy and/or immunotherapy, and G-CSF was most commonly used in those who received rituximab plus multiple chemotherapy regimens (77%). Subsequent MDS/AML diagnoses were identified in 666 patients (3.7%). A modest increased risk of MDS/AML was observed with the receipt of G-CSF (HR, 1.28; 95% CI, 1.01-1.62) and a trend was observed with increasing doses (Ptrend < .01). When specific agents were analyzed, an increased risk of MDS/AML was consistently observed with filgrastim (≥10 doses: HR, 1.67; 95% CI, 1.25-2.23), but not with pegfilgrastim (≥10 + doses: HR, 1.11; 95% CI, 0.84-1.45). CONCLUSIONS: A higher of MDS/AML was observed in patients with NHL risk among those who received G-CSF that was specific to the use of filgrastim (≥10 doses), but not pegfilgrastim. Neutropenia prophylaxis is an essential component of highly effective NHL treatment regimens. The differential risk related to the types of G-CSF agents used warrants further study given their increasing use and newly available, US Food and Drug Administration-approved, biosimilar products.

Blood transfusion history and risk of non-Hodgkin lymphoma: an InterLymph pooled analysis.

PURPOSE: To conduct a pooled analysis assessing the association of blood transfusion with risk of non-Hodgkin lymphoma (NHL). METHODS: We used harmonized data from 13 case-control studies (10,805 cases, 14,026 controls) in the InterLymph Consortium. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, adjusted for study design variables. RESULTS: Among non-Hispanic whites (NHW), history of any transfusion was inversely associated with NHL risk for men (OR 0.74; 95% CI 0.65-0.83) but not women (OR 0.92; 95% CI 0.83-1.03), pheterogeneity = 0.014. Transfusion history was not associated with risk in other racial/ethnic groups. There was no trend with the number of transfusions, time since first transfusion, age at first transfusion, or decade of first transfusion, and further adjustment for socioeconomic status, body mass index, smoking, alcohol use, and HCV seropositivity did not alter the results. Associations for NHW men were stronger in hospital-based (OR 0.56; 95% CI 0.45-0.70) but still apparent in population-based (OR 0.84; 95% CI 0.72-0.98) studies. CONCLUSIONS: In the setting of a literature reporting mainly null and some positive associations, and the lack of a clear methodologic explanation for our inverse association restricted to NHW men, the current body of evidence suggests that there is no association of blood transfusion with risk of NHL.

Tumor necrosis factor-alpha inhibitors and risk of non-Hodgkin lymphoma in a cohort of adults with rheumatologic conditions.

Based on limited evidence, the U.S. Food and Drug Administration (FDA) issued a black box warning for the use of tumor necrosis factor-alpha inhibitors (TNFIs) and risk of non-Hodgkin lymphoma (NHL). Our objective was to determine the risk of NHL associated with TNFI use by duration and type of anti-TNF agent. We performed a nested case-control study within a retrospective cohort of adults with rheumatologic conditions from a U.S. commercial health insurance database between 2009 and 2015. Use of TNFIs (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol) and conventional-synthetic disease-modifying antirheumatic drugs (csDMARDs) was identified, and conditional logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL. From a retrospective cohort of 55,446 adult patients, 101 NHL cases and 984 controls matched on age, gender and rheumatologic indication were included. Compared to controls, NHL cases had greater TNFI use (33% vs. 20%) but were similar in csDMARD use (70% vs. 71%). TNFI ever-use was associated with nearly two-fold increased risk of NHL (OR = 1.93; 95% CI: 1.16-3.20) with suggestion of increasing risk with duration (P-trend = 0.05). TNF fusion protein (etanercept) was associated with increased NHL risk (OR = 2.73; 95% CI: 1.40-5.33), whereas risk with anti-TNF monoclonal antibodies was not statistically significant (OR = 1.77; 95% CI: 0.87-3.58). In sensitivity analyses evaluating confounding by rheumatologic disease severity, channeling bias was not likely to account for our results. Our findings support the FDA black box warning for NHL. Continued surveillance and awareness of this rare but serious adverse outcome are warranted with new TNFIs and biosimilar products forthcoming.

Evaluation of Automatically Assigned Job-Specific Interview Modules.

OBJECTIVE: In community-based epidemiological studies, job- and industry-specific 'modules' are often used to systematically obtain details about the subject's work tasks. The module assignment is often made by the interviewer, who may have insufficient occupational hygiene knowledge to assign the correct module. We evaluated, in the context of a case-control study of lymphoid neoplasms in Asia ('AsiaLymph'), the performance of an algorithm that provided automatic, real-time module assignment during a computer-assisted personal interview. METHODS: AsiaLymph's occupational component began with a lifetime occupational history questionnaire with free-text responses and three solvent exposure screening questions. To assign each job to one of 23 study-specific modules, an algorithm automatically searched the free-text responses to the questions 'job title' and 'product made or services provided by employer' using a list of module-specific keywords, comprising over 5800 keywords in English, Traditional and Simplified Chinese. Hierarchical decision rules were used when the keyword match triggered multiple modules. If no keyword match was identified, a generic solvent module was assigned if the subject responded 'yes' to any of the three solvent screening questions. If these question responses were all 'no', a work location module was assigned, which redirected the subject to the farming, teaching, health professional, solvent, or industry solvent modules or ended the questions for that job, depending on the location response. We conducted a reliability assessment that compared the algorithm-assigned modules to consensus module assignments made by two industrial hygienists for a subset of 1251 (of 11409) jobs selected using a stratified random selection procedure using module-specific strata. Discordant assignments between the algorithm and consensus assignments (483 jobs) were qualitatively reviewed by the hygienists to evaluate the potential information lost from missed questions with using the algorithm-assigned module (none, low, medium, high). RESULTS: The most frequently assigned modules were the work location (33%), solvent (20%), farming and food industry (19%), and dry cleaning and textile industry (6.4%) modules. In the reliability subset, the algorithm assignment had an exact match to the expert consensus-assigned module for 722 (57.7%) of the 1251 jobs. Overall, adjusted for the proportion of jobs in each stratum, we estimated that 86% of the algorithm-assigned modules would result in no information loss, 2% would have low information loss, and 12% would have medium to high information loss. Medium to high information loss occurred for <10% of the jobs assigned the generic solvent module and for 21, 32, and 31% of the jobs assigned the work location module with location responses of 'someplace else', 'factory', and 'don't know', respectively. Other work location responses had ≤8% with medium to high information loss because of redirections to other modules. Medium to high information loss occurred more frequently when a job description matched with multiple keywords pointing to different modules (29-69%, depending on the triggered assignment rule). CONCLUSIONS: These evaluations demonstrated that automatically assigned modules can reliably reproduce an expert's module assignment without the direct involvement of an industrial hygienist or interviewer. The feasibility of adapting this framework to other studies will be language- and exposure-specific.

Epidemiology and etiology of non-hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) consists of many histologically and biologically distinct lymphoid malignancies with poorly understood, but possibly distinct, etiologies. The patterns of incidence and time trend vary not only by age, sex, and race/ethnicity in the USA, but also show significant geographic differences, suggesting the potential role of infectious agents, environmental factors, and lifestyle factors in addition to host genetic status in the development of NHL. Important pathogenetic mechanisms include immune modulation and chronic antigen stimulation. Epidemiologic studies in the past two decades have provided intriguing new insights on the possible causes of lymphoma and support the idea that there is some mechanistic commonality of lymphomagenesis, but significant etiologic heterogeneity clearly exists. This review presents a summary of the current understanding of the descriptive epidemiology and etiology of NHL and suggests areas of focus for future epidemiologic research.

The impact of race, age, and sex in follicular lymphoma: A comprehensive SEER analysis across consecutive treatment eras.

The impact of race/ethnicity and the additional factors of age, sex, and socioeconomic status (SES) on follicular lymphoma (FL) outcomes have not been comprehensively studied and are not well defined. We examined population-based FL data from >18,000 patients in SEER-13 (1992-2009) investigating race/ethnicity and the impact of relevant factors including sex, age, and SES. Further, we compared data over two consecutive periods: Era-1 (1992-2000, n = 8,355) and Era-2 (2001-2009, n = 10,475). We identified 18,830 FL patients (White: n = 15,116; Hispanic: n = 1,627; Asian/Pacific Islander (A/PI): n = 1,002; and Black: n = 846). Median ages (years) differed significantly by race/ethnicity: White: 62.1, Hispanic: 57.3, A/PI: 60.7, and Black: 56.8 (P < 0.01 each race versus White). Overall survival (OS) was superior in Era-2 versus Era-1 for all patients (5-year: 76.7% versus 67.4%, respectively, P < 0.001). Further, survival was significantly improved for all age groups <80 years, for males (P = 0.0019), and females (P < 0.001) across eras. Females had superior OS compared with males in Era-1 (P = 0.004), but not in Era-2. Additionally, all races, except A/PI, had improved 5-year OS rates from Era-1 to Era-2. Finally, OS improved across eras for lower and higher SES populations; however those with higher SES were superior to lower SES patients in both eras. In conclusion, and in the largest comprehensive evaluation of US-based FL patients to date, we show that despite improvements in OS for FL over time, critical disparities across races/ethnicities, sex, and age groups remain in the modern era and warrant further studies.

Dietary patterns and the risk of non-Hodgkin lymphoma.

OBJECTIVE: Previous studies examining the role of single foods or nutrients in the aetiology of non-Hodgkin lymphoma (NHL) have produced inconsistent findings. Few studies have examined associations for dietary patterns, which may more accurately reflect patterns of consumption and the complexity of dietary intake. The objective of the present study was to examine whether dietary patterns identified by factor analysis were associated with NHL risk. DESIGN: Case-control. SETTING: Population-based sample residing in Nebraska from 1999 to 2002. SUBJECTS: A total of 336 cases and 460 controls. RESULTS: Factor analysis identified two major dietary patterns: (i) a 'Meat, Fat and Sweets' dietary pattern characterized by high intakes of French fries, red meat, processed meat, pizza, salty snacks, sweets and desserts, and sweetened beverages; and (ii) a 'Fruit, Vegetables and Starch' dietary pattern characterized by high intakes of vegetables, fruit, fish, and cereals and starches. In multivariable logistic regression models, the 'Meat, Fat and Sweets' dietary pattern was associated with an increased risk of overall NHL (ORQ4 v. Q1 = 3·6, 95 % CI 1·9, 6·8; P trend = 0·0004), follicular lymphoma (ORQ4 v. Q1 = 3·1, 95 % CI 1·2, 8·0; P trend = 0·01), diffuse large B-cell lymphoma (ORQ4 v. Q1 = 3·2, 95 % CI 1·1, 9·0; P trend = 0·09) and marginal zone lymphoma (ORQ4 v. Q1 = 8·2, 95 % CI 1·3, 51·2; P trend = 0·05). No association with overall or subtype-specific risk was detected for the 'Fruit, Vegetables and Starch' dietary pattern. No evidence of heterogeneity was detected across strata of age, sex, BMI, smoking status or alcohol consumption. CONCLUSIONS: Our results suggest that a dietary pattern high in meats, fats and sweets may be associated with an increased risk of NHL.

Relative validity and reproducibility of a quantitative FFQ for assessing nutrient intakes of vegetarians in Taiwan.

OBJECTIVE: To assess the relative validity and reproducibility of the quantitative FFQ used in the Tzu Chi Health Study (TCHS). DESIGN: The reproducibility was evaluated by comparing the baseline FFQ with the 2-year follow-up FFQ. The validity was evaluated by comparing the baseline FFQ with 3 d dietary records and biomarkers (serum folate and vitamin B12). Median comparison, cross-classification and Spearman correlation with and without energy adjustment and deattenuation for day-to-day variation were assessed. SETTING: TCHS is a prospective cohort containing a high proportion of true vegetarians and part-time vegetarians (regularly consuming a vegetarian diet without completely avoiding meat). SUBJECT: Subsets of 103, seventy-eight and 1528 TCHS participants were included in the reproducibility, dietary record-validity and biomarker-validity studies, respectively. RESULTS: Correlations assessing the reproducibility for repeat administrations of the FFQ were in the range of 0·46-0·65 for macronutrients and 0·35-0·67 for micronutrients; the average same quartile agreement was 40%. The correlation between FFQ and biomarkers was 0·41 for both vitamin B12 and folate. Moderate to good correlations between the baseline FFQ and dietary records were found for energy, protein, carbohydrate, saturated and monounsaturated fat, fibre, vitamin C, vitamin A, K, Ca, Mg, P, Fe and Zn (average crude correlation: 0·47 (range: 0·37-0·66); average energy-adjusted correlation: 0·43 (range: 0·38-0·55); average energy-adjusted deattenuated correlation: 0·50 (range: 0·44-0·66)) with same quartile agreement rate of 39% (range: 35-45%), while misclassification to the extreme quartile was rare (average: 4% (range: 0-6%)). CONCLUSIONS: The FFQ is a reliable and valid tool to rank relative intake of major nutrients for TCHS participants.

LABS: linear amplification-based bisulfite sequencing for ultrasensitive cancer detection from cell-free DNA.

Methylation-based liquid biopsies show promises in detecting cancer using circulating cell-free DNA; however, current limitations impede clinical application. Most assays necessitate substantial DNA inputs, posing challenges. Additionally, underrepresented tumor DNA fragments may go undetected during exponential amplification steps of traditional sequencing methods. Here, we report linear amplification-based bisulfite sequencing (LABS), enabling linear amplification of bisulfite-treated DNA fragments in a genome-wide, unbiased fashion, detecting cancer abnormalities with sub-nanogram inputs. Applying LABS to 100 patient samples revealed cancer-specific patterns, copy number alterations, and enhanced cancer detection accuracy by identifying tissue-of-origin and immune cell composition.

Phytanic acid and the risk of non-Hodgkin lymphoma.

Greater consumption of red meat, processed meat and dairy products has been associated with an increased risk of non-Hodgkin lymphoma (NHL) in several previous reports. Phytanic acid, a saturated fatty acid obtained primarily through the consumption of ruminant meat and dairy products, may offer a potential underlying mechanism for these associations. In a population-based case-control study of 336 cases and 460 controls conducted in Nebraska during 1999-2002, we examined whether phytanic acid-containing foods or total phytanic acid intake, estimated from a food frequency questionnaire and the published phytanic acid values of 151 food items, were associated with increased NHL risk. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals for overall NHL and the common NHL histologic subtypes. In multivariable models, higher intakes of density-adjusted beef [OR(T3 vs. T1) = 1.5 (1.1-2.2); P(trend) = 0.02], total dairy products [OR = 1.5 (1.1-2.2); P(trend) = 0.02) and milk [OR = 1.6 (1.1-2.3); P(trend) = 0.01] were associated with an increased risk of NHL. Intake of total phytanic acid was positively associated with NHL risk [OR = 1.5 (1.0-2.1); P(trend) = 0.04]. In analyses stratified by NHL subtype, greater consumption of beef was associated with an increased risk of diffuse large B-cell lymphoma, and greater consumption of milk was associated with an increased risk of follicular lymphoma (FL). Total phytanic acid intake was associated with an increased risk of FL and small lymphocytic lymphoma/chronic lymphocytic leukemia. Our results provide support that total phytanic acid and phytanic acid-containing foods may increase NHL risk.

Pre-diagnosis cigarette smoking and overall survival in non-Hodgkin lymphoma.

We examined whether smoking prior to non-Hodgkin lymphoma (NHL) diagnosis was associated with overall survival (OS) and conducted a meta-analysis to assess the evidence relating pre-diagnosis cigarette smoking with OS. Among 523 NHL patients, worse OS was suggested for greater pre-diagnostic smoking habits when compared to never smokers. In the meta-analysis (n = 5 patient populations), inferior OS was observed for greater number of cigarettes smoked per day, years of cigarette smoking, and pack-years of cigarette smoking. The inferior survival was more pronounced for follicular than for diffuse large B cell lymphoma. Pre-diagnosis cigarette smoking may adversely impact the survival of NHL patients.

Smoking, variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma: a pooled analysis within the InterLymph consortium.

PURPOSE: Studies of smoking and risk of non-Hodgkin lymphoma (NHL) have yielded inconsistent results, possibly due to subtype heterogeneity and/or genetic variation impacting the metabolism of tobacco-derived carcinogens, including substrates of the N-acetyltransferase enzymes NAT1 and NAT2. METHODS: We conducted a pooled analysis of 5,026 NHL cases and 4,630 controls from seven case-control studies in the international lymphoma epidemiology consortium to examine associations between smoking, variation in the N-acetyltransferase genes NAT1 and NAT2, and risk of NHL subtypes. Smoking data were harmonized across studies, and genetic variants in NAT1 and NAT2 were used to infer acetylation phenotype of the NAT1 and NAT2 enzymes, respectively. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for risk of NHL and subtypes were calculated using joint fixed effects unconditional logistic regression models. RESULTS: Current smoking was associated with a significant 30 % increased risk of follicular lymphoma (n = 1,176) but not NHL overall or other NHL subtypes. The association was similar among NAT2 slow (OR 1.36; 95 % CI 1.07-1.75) and intermediate/rapid (OR 1.27; 95 % CI 0.95-1.69) acetylators (p (interaction) = 0.82) and also did not differ by NAT1*10 allelotype. Neither NAT2 phenotype nor NAT1*10 allelotype was associated with risk of NHL overall or NHL subtypes. CONCLUSION: The current findings provide further evidence for a modest association between current smoking and follicular lymphoma risk and suggest that this association may not be influenced by variation in the N-acetyltransferase enzymes.