Associations between statin use and non‐Hodgkin lymphoma (NHL) risk and survival: a meta‐analysis

Evidence on the effect of statin use on non‐Hodgkin lymphoma (NHL) is not clear. We conducted a systematic review and meta‐analysis to examine the associations between statin use and NHL risk and survival. We searched multiple literature sources up to October 2014 and identified 10 studies on the risk of diagnosis with NHL and 9 studies on survival. Random effects model was used to calculate pooled odds ratio (PORs) for risk and pooled hazard ratio (PHR) for survival. Heterogeneity among studies was examined using the Tau‐squared and the I‐squared (I²) tests. Statin use was associated with reduced risk for total NHL (POR = 0.82, 95% CI 0.69–0.99). Among statin users, there was a lower incidence risk for marginal zone lymphoma (POR = 0.54, 95% CI 0.31–0.94), but this was not observed for other types of NHL. However, statin use did not affect overall survival (PHR = 1.02, 95% CI 0.99–1.06) or event‐free survival (PHR = 0.99, 95% CI 0.87–1.12) in diffuse large B‐cell lymphoma. There is suggestive epidemiological evidence that statins decrease the risk of NHL, but they do not influence survival in NHL patients. Copyright © 2015 John Wiley & Sons, Ltd.     

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.     

Relationship between ambient ultraviolet radiation and non‐Hodgkin lymphoma subtypes: A U.S. population‐based study of racial and ethnic groups

Associations between ultraviolet radiation (UVR) exposure and non‐Hodgkin lymphoma (NHL) have been inconsistent, but few studies have examined these associations for specific subtypes or across race/ethnicities. We evaluated the relationship between ambient UVR exposure and subtype‐specific NHL incidence for whites, Hispanics and blacks in the United States for years 2001–2010 (n = 187,778 cases). Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for UVR quintiles using Poisson regression. Incidence was lower for the highest UVR quintile for chronic/small lymphocytic/leukemia (CLL/SLL) (IRR = 0.87, 95% CI: 0.77–0.97), mantle cell (IRR = 0.82, 95% CI: 0.69–0.97), lymphoplasmacytic (IRR = 0.58, 95% CI: 0.42–0.80), mucosa‐associated lymphoid tissue (MZLMALT) (IRR = 0.74, 95% CI: 0.60–0.90), follicular (FL) (IRR = 0.76, 95% CI: 0.68–0.86), diffuse large B‐cell (IRR = 0.84, 95% CI: 0.76–0.94;), peripheral T‐cell other (PTCL) (IRR = 0.76, 95% CI: 0.61–0.95) and PTCL not otherwise specified (PNOS) (IRR = 0.77, 95% CI: 0.61–0.98). Trends were significant for MZLMALT, FL, DLBCL, BNOS and PTCL, with FL and DLBCL still significant after Bonferroni correction. We found interaction by race/ethnicity for CLL/SLL, FL, Burkitt, PNOS and MF/SS, with CLL/SLL and FL still significant after Bonferroni correction. Some B‐cell lymphomas (CLL/SLL, FL and Burkitt) suggested significant inverse relationships in whites and Hispanics, but not in blacks. Some T‐cell lymphomas suggested the most reduced risk for the highest quintile of UVR among blacks (PNOS and MF/SS), though trends were not significant. These findings strengthen the case for an inverse association of UVR exposure, support modest heterogeneity between NHL subtypes and suggest some differences by race/ethnicity.     

A prospective analysis of circulating saturated and monounsaturated fatty acids and risk of non‐Hodgkin lymphoma

Circulating saturated (SFA) and monounsaturated fatty acids (MUFA), which are predominantly derived from endogenous metabolism, may influence non‐Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. However, few biomarker studies have evaluated NHL risk associated with these fats. We conducted a prospective study of 583 incident NHL cases and 583 individually matched controls with archived pre‐diagnosis red blood cell (RBC) specimens in the Nurses’ Health Study (NHS) and Health Professionals Follow‐Up Study (HPFS). RBC membrane fatty acid levels were measured using gas chromatography. Using multivariable logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL and major NHL subtypes including T cell NHL (T‐NHL), B cell NHL (B‐NHL) and three individual B‐NHLs: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B‐cell lymphoma (DLBCL) and follicular lymphoma. RBC SFA and MUFA levels were not associated with NHL risk overall. However, RBC very long chain SFA levels (VLCSFA; 20:0, 22:0, 23:0) were inversely associated with B‐NHLs other than CLL/SLL; ORs (95% CIs) per standard deviation (SD) increase in level were 0.81 (0.70, 0.95) for 20:0, 0.82 (0.70, 0.95) for 22:0 and 0.82 (0.70, 0.96) for 23:0 VLCSFA. Also, both VLCSFA and MUFA levels were inversely associated with T‐NHL [ORs (95% CIs) per SD: VLCSFA, 0.63 (0.40, 0.99); MUFA, 0.63 (0.40, 0.99)]. The findings of inverse associations for VLCSFAs with B‐NHLs other than CLL/SLL and for VLCSFA and MUFA with T‐NHL suggest an influence of fatty acid metabolism on lymphomagenesis.     

Epstein‐Barr virus and risk of non‐Hodgkin lymphoma in the cancer prevention study‐II and a meta‐analysis of serologic studies

Epstein‐Barr virus (EBV) causes rare, malignant lymphomas. The role of EBV in other non‐Hodgkin lymphomas (NHLs) remains unclear, but mildly reduced immune function could lead to reactivation of EBV and subsequent NHL. We examined the association between prospectively‐collected plasma EBV antibodies and NHL risk in the Cancer Prevention Study‐II (CPS‐II) Nutrition Cohort and conducted a meta‐analysis of our and published results. The CPS‐II study included 225 NHL cases and 2:1 matched controls. No associations were observed between EBV serostatus or antibody levels and risk of NHL overall. However, when including only the three most common types of NHL (diffuse large B‐cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma), high compared to low early antigen (EA‐D) diffuse and BZLF1‐encoded replication activator antibodies were associated with approximately 60% higher risk of NHL. Odds ratios (ORs) for EBV nuclear antigen‐1 and viral capsid antigen (VCA)‐p18 were elevated but not statistically significant. In the meta‐analysis, both EA (summary OR = 1.52, 95% confidence interval (CI): 1.16–2.00) and VCA (summary OR = 1.20, 95% CI: 1.00–1.44) were positively associated with NHL risk. These results suggest EBV may be associated with a wider spectrum of NHL subtypes, but further study is needed to confirm and fully understand these associations.     

Fruits and vegetables consumption and risk of non‐Hodgkin's lymphoma: A meta‐analysis of observational studies

Epidemiologic evidence suggests that intakes of fruits and/or vegetables may play a role in the etiology of non‐Hodgkin's lymphoma (NHL), but the findings are inconsistent. We aimed to assess fruits and/or vegetables intakes in relation to risk of NHL by a meta‐analytic approach. We searched on PubMed database from January 1966 to September 2012 to indentify case‐control and cohort studies. We used a random‐effects model to compute summary risk estimates. For vegetables, the summary relative risks (RRs) of NHL for high versus low intake for case‐control, cohort and all studies were 0.75 (95% CI, 0.60–0.94; N = 8), 0.90 (95% CI, 0.81–1.00; N = 5) and 0.81 (95%CI, 0.71–0.92; N = 13) ; and the corresponding RRs for intake of 1 serving per day were 0.88 (95% CI, 0.80–0.96; N = 8), 0.96 (95% CI, 0.92–1.00; N = 5) and 0.92 (95%CI, 0.87–0.96; N = 13). For fruits and vegetables combined, the summary RR for high versus low intake was 0.78 (95%CI, 0.66–0.92; N = 4), and for intake of 1 serving per day was 0.95 (95%CI, 0.91–1.00; N = 4). Regarding histological subtypes, vegetables intake was significantly inversely associated with diffuse large B‐cell lymphoma and follicular lymphoma, but not small lymphocytic lymphoma/chronic lymphocytic leukemia (high vs. low intake, RR = 0.70, 0.70 and 1.01, respectively; N = 7, 7 and 10, respectively). Fruits intake was generally not associated with total NHL, or any histological subtypes. Our findings suggest that intakes of vegetables, and fruits and vegetables combined, but not fruits alone, significantly reduce risk of NHL.     

Cardiovascular mortality among patients with non‐Hodgkin lymphoma: Differences according to lymphoma subtype

Survival rates of patients with non‐Hodgkin lymphoma (NHL) have improved over the last decade. However, cardiotoxicities remain important adverse consequences of treatment with chemotherapy and radiation, although the burden of cardiovascular mortality (CVM) in such patients remains unknown. We conducted a retrospective cohort study of patients greater than or equal to 20 years of age diagnosed with diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) between 2000 and 2013 using data extracted from the United States Surveillance, Epidemiology, and End Results (SEER) database. Our primary endpoint was CVM. The association between NHL and CVM was evaluated using multivariable Cox regression analysis after adjusting for other patient characteristics. We calculated standardized mortality ratios (SMRs) for CVM, comparing NHL patients with the general population. We identified 153 983 patients who met the inclusion criteria (69 329 with DLBCL, 48 650 with CLL/SLL, and 36 004 with FL). The median follow‐up was 37 months (interquartile range, 10‐78 months); the mean patient age was 66.24 (±14.69) years; 84 924 (55.2%) were men; 134 720 (87.5%) were White, and 131 912 (85.7%) did not receive radiation therapy. Overall, 9017 patients (5.8%) died from cardiovascular disease, and we found that NHL patients had a higher risk of CVM than the general population, after adjusting for age (SMR 15.2, 95% confidence interval: 14.89‐15.52). The rates of CVM were 5.1%, 8%, and 4.4% in patients with DLBCL, CLL/SLL, and FL, respectively. Furthermore, across all NHL subtypes, older age, higher stage at the time of diagnosis (particularly stage 4), male sex, and living in the south were associated with higher risks of CVM. Our data suggest that risk assessment and careful cardiac monitoring are recommended for NHL patients, particularly those with the CLL/SLL subtypes.     

Analgesic use and the risk of kidney cancer: A meta‐analysis of epidemiologic studies

Analgesics are the most commonly used over‐the‐counter drugs worldwide with certain analgesics having cancer prevention effect. The evidence for an increased risk of developing kidney cancer with analgesic use is mixed. Using a meta‐analysis design of available observational epidemiologic studies, we investigated the association between analgesic use and kidney cancer risk. We searched the MEDLINE and EMBASE databases to identify eligible case–control or cohort studies published in English until June 2012 for three categories of analgesics: acetaminophen, aspirin or other non‐steroidal anti‐inflammatory drugs (NSAIDs). Study‐specific effect estimates were pooled to compute an overall relative risk (RR) and its 95% confidence interval (CI) using a random‐effects model for each category of the analgesics. We identified 20 studies (14 with acetaminophen, 13 with aspirin and five with other NSAIDs) that were performed in six countries, including 8,420 cases of kidney cancer. Use of acetaminophen and non‐aspirin NSAIDs were associated with an increased risk of kidney cancer (pooled RR: 1.28; 95% CI: 1.15–1.44 and 1.25; 95% CI: 1.06–1.46, respectively). For aspirin use, we found no overall increased risk (pooled RR: 1.10; 95% CI: 0.95–1.28), except for non‐US studies (five studies, pooled RR: 1.17; 95% CI: 1.04–1.33). Similar increases in risks were seen with higher analgesic intake. In this largest meta‐analysis to date, we found that acetaminophen and non‐aspirin NSAIDs are associated with a significant risk of developing kidney cancer. Further work is needed to elucidate biologic mechanisms behind these findings.     

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.     

N‐acetyltransferase polymorphisms are associated with risk of lymphoma subtypes

Genes encoding for arylamine N‐acetyltransferase 1 and 2 (NAT1 and NAT2) have been investigated with alternate findings in relation to risk of non‐Hodgkin lymphoma (NHL). We tested functional haplotype‐based NAT1 and NAT2 gene polymorphisms in relation to risk of lymphoma overall and its major B cell subtypes, diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia (CLL). We used allele specific primers and multiplex PCR to detect NAT1 and NAT2 haplotypes in 248 patients with incident lymphoma and 208 population controls. We inferred the NAT1 rapid and slow acetylator and the NAT2 rapid, intermediate or slow acetylator phenotype, based on published functional data on the respective genotypes. Odds ratios and 95% confidence intervals (95% CIs) for lymphoma, B‐NHL, DLBCL, FL, CLL, and other B‐NHL combined associated with the inferred rapid NAT1 acetylator and with the intermediate and slow NAT2 acetylator phenotypes were estimated with unconditional and polytomous logistic regression analysis, adjusting for age, gender and education. NAT1 rapid acetylators showed a 2.8‐fold excess risk (95% CI 1.5–5.2) for lymphoma (all subtypes combined). Risk was highest for CLL and FL, with significant heterogeneity detected across subtypes. Risk also increased with decreasing NAT2 acetylating capacity with no heterogeneity detected across B cell lymphoma subtypes. Risks did not vary by gender. Although poor statistical power was a major limitation in our study, larger studies and pooled analyses are warranted to test whether NAT1 and NAT2 gene polymorphisms might modulate risk of specific lymphoma subtypes through the varying metabolic activity of their products. Copyright © 2015 John Wiley & Sons, Ltd.     

Lifetime alcohol intake and risk of non‐Hodgkin lymphoma: Findings from the Melbourne Collaborative Cohort Study

Cohort studies have reported inconsistent evidence regarding alcohol intake and risk of non‐Hodgkin lymphoma (NHL), mostly based on alcohol intake assessed close to study enrolment. We examined this association using alcohol intake measured from age 20 onwards. We calculated usual alcohol intake for 10‐year periods from age 20 using recalled frequency and quantity of beverage‐specific consumption for 37,990 participants aged 40–69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between alcohol intake (g/day) and NHL risk. After a mean follow‐up of 19.3 years, 538 NHL cases were diagnosed. Approximately 80% of participants were either lifetime abstainers or consumed below 20 g of ethanol/day. All categories of lifetime alcohol intake were associated with about 20% lower incidence of NHL compared with lifetime abstention, but there was no evidence of a trend by amount consumed (HR = 0.97 per 10 g/day increment in intake, 95% CI: 0.92–1.03; p value = 0.3). HRs for beer, wine and spirits were 0.91 (95% CI: 0.83–1.00; p value = 0.05), 1.03 (95% CI: 0.94–1.12; p value = 0.6), and 1.06 (95% CI: 0.83–1.37; p value = 0.6), respectively, per 10 g/day increment in lifetime intake. There were no significant differences in associations between NHL subtypes. In this low‐drinking cohort, we did not detect a dose‐dependent association between lifetime alcohol intake and NHL risk.     

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.     

Alcohol consumption and risk of hematological malignancies: A meta‐analysis of prospective studies

Current convincing evidence suggests that alcohol intake increases the risk of several carcinomas, which might subsequently lead to a recommendation toward limiting alcohol consumption. However, there are accumulating data worth meta‐analyzing that show a different effect on the risk of hematological malignancies. Eligible cohort studies were sought in PubMed database up to August 31, 2016. Separate analyses were performed by subtype of hematological malignancy (non‐Hodgkin lymphoma [NHL] and subtypes, Hodgkin lymphoma [HL], leukemia and subtypes), time status (ever, current, former), level of consumption (light, moderate, heavy), alcoholic beverage (total alcohol, beer, liquor, wine) and gender. Moderate and heavy alcohol consumption were significantly associated with reduced risk of NHL (relative risk [RR] = 0.85, 95% confidence interval [CI]: 0.80–0.90 and RR = 0.73, 95%CI: 0.60–0.89, respectively); a protective trend was also shown for light alcohol intake (RR = 0.93, 95%CI: 0.87–1.00). Specifically, beer consumption was associated with reduced NHL risk (RR = 0.88, 95%CI: 0.81–0.95). However, the association regarding other alcoholic beverages seemed null. The beneficial effects of alcohol mainly pertained to Diffuse Large B‐Cell Lymphoma (DLBCL) (RR = 0.83, 95%CI: 0.77–0.89) and Follicular Lymphoma (FL) (RR = 0.85, 95%CI: 0.78–0.93). There was also no association between alcohol consumption and risk of HL or leukemias. In contrast to most solid malignancies, alcohol seems to confer a protective effect on NHL risk, especially on DLBCL and FL subtypes, with beer being notably beneficial.     

Aspirin,nonsteroidal anti‐inflammatory drugs,paracetamol and risk of endometrial cancer: A case–control study,systematic review and meta‐analysis

Aspirin and other nonsteroidal anti‐inflammatory drugs (NSAIDs) have been associated with reduced risk of a number of cancer types, however, previous studies of endometrial cancer have yielded inconclusive results. We analyzed data from the Australian National Endometrial Cancer Study (ANECS), a population‐based case–control study (1,398 cases, 740 controls). We systematically reviewed all the evidence linking aspirin/NSAIDs use with endometrial cancer and conducted a meta‐analysis. For ANECS, unconditional logistic regression was used to estimate odds ratios (OR) adjusting for potential confounders. For the systematic review, we searched Pubmed, Embase, Web of Science and conducted a review of citations from retrieved articles. The meta‐analysis risk estimates were pooled using a random‐effects model. In our case–control study, women who had ever used aspirin in the last 5 years had a significantly lower risk of endometrial cancer OR = 0.78 [95% confidence interval (CI): 0.63‐0.97]. There was a significant inverse dose–response (p‐trend <0.001) such that women who reported using ≥2 aspirin/week had almost half the risk OR = 0.54 (0.38–0.78). No significant associations were observed between use of half‐aspirin/day, non‐aspirin NSAIDs or paracetamol and endometrial cancer risk. The results were similar when examined by cancer subtype. Nine studies were included in the meta‐analysis. The overall pooled risk estimate for any versus no use of aspirin was 0.87 (0.79–0.96) with no evidence of heterogeneity. The pooled risk estimate for obese women (BMI ≥ 30 kg/m²) was 0.72 (0.58–0.90) but there was no association for non‐obese women. Overall these results suggest that aspirin may reduce the risk of endometrial cancer, particularly among obese women.     

Lifestyle factors,autoimmune disease and family history in prognosis of non‐hodgkin lymphoma overall and subtypes

Lifestyle factors and medical history are known to influence risk of non‐Hodgkin lymphoma (NHL). Whether these factors affect the prognosis of NHL, especially its subtypes, is unclear. To investigate this, the association between these factors and all‐cause and lymphoma‐related mortality was assessed in a population‐based cohort of 1,523 Swedish NHL patients included in the Scandinavian Lymphoma Etiology study in 1999–2002. Participants contributed time from NHL diagnosis until death or October 1, 2010, with virtually complete follow‐up through linkage to the Swedish Cause of Death Register. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using stratified and multivariable‐adjusted Cox regression models. During a median follow‐up of 8.8 years, 670 patients (44%) died, with the majority of deaths attributed to lymphoma (86%). Current versus never smoking at diagnosis was associated with increased rate of all‐cause death for all NHL (HR = 1.5, 1.2–1.8) and diffuse large B‐cell lymphoma (HR = 1.8, 1.2–2.7). Low educational level (HR = 1.3, 1.1–1.7, <9 vs. >12 years) and NHL risk‐associated autoimmune disease (HR = 1.4, 1.0–1.8) were associated with death for all NHL combined. However, evidence of an association with lymphoma‐related death was limited. Body mass index, recent sunbathing and family history of hematopoietic malignancy were not consistently associated with death after NHL or its specific subtypes. These results add to the evidence that cigarette smoking, socioeconomic status and certain autoimmune diseases affect survival after NHL. Further investigations are needed to determine how these factors should be incorporated into clinical prognostic assessment.     

Serologic markers of viral infection and risk of non‐Hodgkin lymphoma: A pooled study of three prospective cohorts in China and Singapore

Incidence rates of non‐Hodgkin lymphoma (NHL) and distributions of certain viruses differ between East Asian and Western populations. There are limited data on associations between serologic markers of multiple viral infections in pre‐diagnostic blood and NHL risk in East Asians. We conducted a nested case‐control study of 214 NHL cases and 214 matched controls from three population‐based prospective cohorts in Shanghai and Singapore. Antibodies against antigens from herpesviruses, Hepatitis B (HBV) and C (HCV) virus and polyomaviruses were measured in plasma or serum using fluorescent bead‐based multiplex assays. Conditional logistic regression was used to evaluate associations between antibody levels and NHL risk. An increased risk of NHL was observed for higher compared to lower EA‐D (Odds Ratio (OR) = 2.04, 95% Confidence Interval (CI) = 1.10‐3.81; p_trend = 0.005) and ZEBRA (OR = 2.17, 95% CI = 0.96‐4.89; p_trend = 0.008) Epstein‐Barr Virus (EBV) antibodies, as well as for antibody seropositivity against the IE1A human herpesvirus‐6 (HHV‐6) antigen (OR = 1.85, 95% CI = 1.04‐3.29). An increased NHL risk was also observed for higher compared to lower antibodies against the HBV‐HBc and HBe antigens. An increased risk of NHL in relation to EBV and HBV infection in East Asians is consistent with findings in several studies of Western populations, suggesting similar viral risk factors for NHL in these diverse populations with distinct patterns of NHL. The association between HHV‐6 antibodies and NHL has not previously been reported in a prospective study in this population and will require replication.     

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.     

Prognostic value of phospho‐Akt in patients with non‐small cell lung carcinoma: A meta‐analysis

Previous studies have been inconsistent with respect to the reported associations between phospho‐Akt (p‐Akt) overexpression and lung cancer prognosis. In this study, we conducted a systematic review and meta‐analysis to assess the prognostic value of p‐Akt in patients with non‐small cell lung carcinoma (NSCLC). Relevant articles were identified by searching MEDLINE. Hazard risks (HRs) from individual studies were calculated and pooled by using a random‐effect model, and heterogeneity and publication bias analyses were also performed. Finally, 18 studies comprising 2,353 patients were included in the meta‐analysis. p‐Akt overexpression was associated with worse survival in NSCLC patients, and the pooled HRs for all the studies was 1.38 (95% confidence interval [CI]: 1.11–1.70; p < 0.01). After subgroup analysis, the association was strengthened in the surgery treatment group, with an HR of 1.44 (95% CI: 1.19–1.75; p < 0.01), while in the tyrosine kinase inhibitors treatment group, the statistical significance disappeared (HR: 1.22, 95% CI: 0.70–2.14; p = 0.48). The HR in cases of early stage disease (I–III) was 1.35 (95% CI: 1.08–1.69; p = 0.04); however, in cases of late stage disease (III–IV), the association became non‐significant (HR: 1.22, 95% CI: 0.64–2.33; p = 0.54). Our results suggest that there was a significantly inverse association between p‐Akt overexpression and the prognosis of NSCLC patients, and that this association appeared to be limited in early‐stage patients who underwent surgery.     

Common genetic variants and risk for non‐Hodgkin lymphoma and adult T‐cell lymphoma/leukemia in Jamaica

We evaluated whether risk of non‐Hodgkin lymphoma (NHL), particularly adult T‐cell leukemia/lymphoma (ATL) related to human T‐lymphotropic virus (HTLV) infection was associated with 63 single nucleotide polymorphisms (SNPs) from 38 candidate genes. The 395 NHL cases registered in Jamaica were matched by age, sex, calendar‐year and HTLV serostatus to 309 controls from the same population. Interleukin 13 (IL13) Ex4+98A>G SNP (rs20541) was associated with decreased NHL risk (OR_AG/AA = 0.62,95% CI = 0.44–0.87, p = 0.006), as was vascular cell adhesion molecule‐1, VCAM1 Ex9+149G>A SNP (rs1041163) (OR_CT = 0.77, 95% CI = 0.54–1.10, OR_CC=0.35, 95% CI = 0.16–0.76, p‐trend = 0.007). Both results were stronger in analyses restricted to ATL cases and HTLV‐positive controls, suggesting a role for these genes in ATL etiology (IL13 OR_AG/AA = 0.54, 95% CI = 0.36–0.84, p = 0.005; VCAM1 OR_CT = 0.65, 95% CI = 0.42–1.01, OR_CC = 0.20, 95% CI = 0.08–0.54, p‐trend = 0.001). Confirmation of these results in Caribbean and other populations is needed. © 2009 UICC