Alcohol consumption and non-Hodgkin lymphoma in a cohort of older women.

We investigated the relation of alcohol consumption to risk of non-Hodgkin's lymphoma (NHL) in a cohort of 35 156 Iowa women aged 55-69 years who participated in the Iowa Women's Health Study in 1986. Alcohol consumption at baseline was obtained using a mailed questionnaire. During the 9-year follow-up period, 143 incident cases of NHL were identified. Higher alcohol consumption was significantly associated with a decreased risk of NHL (P-trend = 0.03). Compared to non-drinkers, multivariate-adjusted relative risks (RRs) were decreased for women with intake of < or = 3.4 g day(-1) (RR = 0.78; 95% confidence interval (CI) 0.51-1.21) and > 3.4 g day(-1) (RR = 0.59; 0.36-0.97). The inverse association could not be attributed to one particular type of alcoholic beverage, although red wine (RR = 0.21 for > 2 glasses per month vs non-drinker; 0.05-0.86; P-trend = 0.02) has the most distinct effect. The apparent protective effect was universal regardless of specific NHL grade or Working Formulation subtype, but was most pronounced for nodal NHL (RR = 0.48; 0.26-0.90; P-trend = 0.01) and low-grade NHL (RR = 0.52; 0.21-1.26; P-trend = 0.05). These data suggest that moderate alcohol consumption is inversely associated with the risk of NHL in older women and the amount of alcohol consumed, rather than the type of alcoholic beverages, appears to be the main effect determinant.     

Cigarette smoking and risk of non-Hodgkin lymphoma subtypes among women

Previous studies of the relationship between cigarette smoking and non-Hodgkin lymphoma (NHL) have yielded conflicting results, perhaps because most studies have evaluated the risk for all NHL subtypes combined. Data from a population-based case-control study conducted among women in Connecticut were used to evaluate the impact of cigarette smoking on the risk of NHL by histologic type, tumour grade, and immunologic type. A total of 601 histologically confirmed, incident cases of NHL and 718 population-based controls provided in-person interviews. A standardised, structured questionnaire was used to collect information on each subject's current smoking status, age at initiation, duration and intensity of smoking, and cumulative lifetime exposure to smoking. Our data suggest that cigarette smoking does not alter the risk of all NHL subtypes combined. However, increased risk of follicular lymphoma appears to be associated with increased intensity and duration of smoking, and cumulative lifetime exposure to smoking. Compared with nonsmokers, women with a cumulative lifetime exposure of 16-33 pack-years and 34 pack-years or greater experience 50% increased risk (OR=1.5, 95% CI 0.9-2.5) and 80% increased risk (OR=1.8, 95% CI 1.1-3.2), respectively, of follicular lymphoma (P for linear trend=0.05). Our study findings are consistent with several previous epidemiologic studies suggesting that cigarette smoking increases the risk of follicular lymphoma. This research highlights the importance of distinguishing between NHL subtypes in future research on the aetiology of NHL.     

Alcohol intake and risk of non-Hodgkin lymphoma in men and women

Objective: The effect of alcohol intake on risk of NHL is unclear. We therefore conducted a population-based case-control study to examine the association between alcohol and NHL risk. Methods: 613 NHL cases and 480 population controls in Sweden reported their average consumption of beer, wine, and liquor 2years before the study. Unconditional logistic regression was used to estimate the odds ratios (OR) and corresponding 95% confidence intervals (CI) for associations between alcohol intake and NHL risk. Results: Intake of total alcohol, beer, wine, or liquor was not associated with risk of overall NHL. There was no difference in risk of NHL among those who habitually consumed above 19.1g of ethanol per day, compared to those who consumed on average 0–2.2g of ethanol per day (OR = 1.2 (95% CI: 0.8, 1.7); p _trend = 0.29). However, the association was significantly positive among males (OR = 1.8 (95% CI: 1.1, 2.9); p _trend = 0.06). Total alcohol, beer, wine, or liquor intake was not associated with any major histopathologic subtype of NHL examined, apart from an association between high wine consumption and increased risk of chronic lymphocytic leukemia. Conclusions: Alcohol does not appear to be a major etiologic factor for overall NHL, nor its common subtypes.     

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.     

Smoking and non-Hodgkin lymphoma: case-control study in Italy

Tobacco smoking is a well-documented risk factor for several cancers, but the role of cigarette smoking in the etiology of non-Hodgkin lymphoma (NHL) is inadequately understood. Hepatitis C virus (HCV) has been associated with NHL, but the interaction between HCV and smoking habits has not yet been studied. Between 1999 and 2002, we conducted a case-control study on the association of HCV, smoking habits and NHL in 2 areas of northern and southern Italy. Cases were 225 consecutive patients (median age, 59 years) with a new diagnosis of NHL that were admitted to reference and general hospitals. Controls were 504 patients (median age, 63 years) admitted to the same hospitals as cases, for a wide spectrum of acute, nonneoplastic, nonimmune-, nor tobacco-related conditions. Current, heavy smokers (> or = 20 cigarettes/day) had an odds ratio (OR) of NHL of 2.10 (95% confidence interval, CI: 1.07-4.12) compared to never smokers. The association between smoking and NHL was consistent across strata of sex and age. Compared to never smokers, current smokers of > or = 20 cigarettes/day had ORs of 1.14 (95% CI: 0.37-3.56) for B-cell-low-grade, 2.10 (95% CI: 0.94-4.67) for B-cell-intermediate and high-grade, and 25.84 (95% CI: 1.95-342.17) for T-cell NHL. The effect of tobacco smoking and HCV were independent on the relative risk, leading a 4-fold elevated risk in current smokers HCV positive subjects. Tobacco smoking and hepatitis C virus (HCV) have been associated to non-Hodgkin lymphoma (NHL), but the interaction between HCV and smoking habits has not yet been studied. Our study confirms that tobacco is related to NHL, and reports on the combined effect of tobacco smoking and HCV. Infection acted together according to a multiplicative model, leading to a 4-fold elevated risk in current smokers HCV positive subjects.     

Organochlorines and risk of non-Hodgkin lymphoma

Organochlorine chemicals and polychlorinated biphenyls (PCBs) have been suspected as possible risk factors for non-Hodgkin lymphoma (NHL). We investigated PCBs and organochlorine pesticides and risk of NHL in a population-based case-control study in British Columbia, Canada. Congeners of PCBs (including dioxinlike congeners) and pesticides or pesticide metabolites were measured in plasma of 422 pretreatment cases and 460 control subjects. This is so far the largest study to examine organochlorines in plasma to date. Several dioxin-like PCB congeners were associated with increased risk of NHL, including dioxin-like PCB nos. 118 and 156 with odds ratios (OR) for the highest versus lowest quartile between 1.6 and 1.8. Several non-dioxin-like congeners also showed significant associations. The PCB congener with the strongest association was no. 180 with an OR for the highest versus the lowest quartile of 1.83 (95% confidence interval = 1.18-2.84). Six pesticide analytes also showed a significant association with NHL; beta-hexachlorocyclohexane, p,p'-DDE, hexachlorobenzene, mirex, oxychlordane and trans-nonachlor. The strongest association was found for oxychlordane, a metabolite of the pesticide chlordane (highest vs. lowest quartile OR = 2.68, 95% confidence interval = 1.69-4.24). Our results provide further evidence that organochlorines contribute to NHL risk.     

Meat intake and risk of non-Hodgkin lymphoma

We conducted a population-based, case-control study to test the hypothesis that consumption of meat and meat-related mutagens increases the risk of non-Hodgkin lymphoma (NHL), and whether the associations are modified by N-acetyltransferase (NAT) 1 and 2. Participants (336 cases and 460 controls) completed a 117-item food frequency questionnaire. The risk of NHL was associated with a higher intake of red meat (OR?=?1.5; CI, 1.1-2.2), total fat (OR?=?1.4; CI, 1.0-2.1), and oleic acid (OR?=?1.5; CI, 1.0-2.2). NHL risk was also associated with a higher intake of very well-done pork (OR?=?2.5; 95?% CI, 1.4-4.3) and the meat-related mutagen MeIQx (OR?=?1.6; 95?% CI, 1.1-2.3). Analyses of the major NHL histologic subtypes showed a positive association between diffuse large B cell lymphoma (DLBCL) and higher intake of red meat (OR?=?2.1; 95?% CI, 1.1-3.9) and the association was largely due to meat-related mutagens as a positive association was observed for higher intakes of both MeIQx (OR?=?2.4; 95?% CI, 1.2-4.6) and DiMeIQx (OR?=?1.9; 95?% CI, 1.0-3.5). Although the OR for follicular lymphoma (FL) was also increased with a higher red meat intake (OR?=?1.9; 95?% CI, 1.1-3.3), the association appeared to be due to increased oleic acid (OR?=?1.7; 95?% CI: 0.9-3.1). We found no evidence that polymorphisms in NAT1 or NAT2 modify the association between NHL and meat-related mutagens. Our results provide further evidence that red meat consumption is associated with an increase in NHL risk, and new evidence that the specific components of meat, namely fat and meat-related mutagens, may be impacting NHL subtype risk differently.     

Hepatitis C virus and risk of non-Hodgkin lymphoma: a population-based case-control study among Connecticut women.

OBJECTIVES: Previous epidemiologic studies of hepatitis C virus (HCV) infection and B-cell non-Hodgkin lymphoma (B-NHL) have yielded conflicting results, perhaps due to differences in the classification of B-NHL and the choice of non-population-based control groups that may not reflect the background population prevalence of HCV. To further investigate the link between HCV and NHL, we conducted HCV testing on serum samples of 998 women (464 cases; 534 controls) from a population-based case-control study of women in Connecticut. METHODS: Serum samples were screened for HCV antibodies using an enzyme immunoassay; positive samples were confirmed by additional testing for HCV antibodies and for serum HCV RNA. RESULTS: Approximately 2% (8 of 464) of cases and 1% (5 of 534) of controls tested positive for HCV. The risk of NHL associated with HCV infection appeared to be concentrated among B-cell lymphomas [odds ratio (OR) 2.0; 95% confidence interval (CI) 0.6, 8.2], particularly among follicular lymphomas (OR 4.1, 95% CI 0.8, 19.4). CONCLUSIONS: The primary strength of this study is our use of a population-based study design, although the low prevalence of HCV among women in Connecticut resulted in wide CIs for the estimated association between HCV and B-NHL subtypes. Our study suggests that HCV may be associated with increased risk of development of B-NHL, and that this risk may vary by B-NHL subtype among women. Due to the relatively low prevalence of HCV in our study population and the scarcity of population-based epidemiological research on this subject, our study highlights the need for additional large, population-based studies of the role of HCV in the etiology of B-NHL.     

Autoimmune diseases associated with non-Hodgkin lymphoma: a nationwide cohort study

BackgroundThe cumulative risk of non-Hodgkin lymphoma (NHL) in Sweden by age 80 years has increased to 1.1 in women and 1.6% in men in 2011. Increased risk of NHL associated with personal histories of some autoimmune diseases (ADs) is known. It is unclear whether there are other NHL-related ADs and whether this association holds across different sex, age and year of diagnosis, or NHL histological subtypes.Patients and methodsOver an average of 9.4-year (maximum 47 years) follow-up of 878 161 patients diagnosed in 1964–2010 with 33 different ADs, 3096 subsequent NHL were diagnosed (data: Swedish Cancer Registry).ResultsOf 33 studied ADs, 21 showed significantly increased risk of NHL; 6 of them tended to increase the risk and none significantly decreased it. The overall standardized incidence ratio (SIR) for NHL after ADs was 1.6 [novel findings: immune thrombocytopenic purpura (ITP) = 7.5, polymyositis/dermatomyositis = 4.1, primary biliary cirrhosis = 3.9, myasthenia gravis = 2.2, Behcet = 1.7, rheumatoid fever = 1.7, ulcerative colitis = 1.5, polymyalgia rheumatica = 1.4, and chronic rheumatic heart disease = 1.4; confirmatory findings: autoimmune hemolytic anemia = 27.2, Sjögren = 4.9, Celiac = 4.8, systemic lupus erythematosus = 4.4, polyarteritis nodosa = 2.9, discoid lupus erythematosus = 2.7, sarcoidosis = 2.6, Crohn = 2.1, systemic sclerosis = 2.1, rheumatoid arthritis = 2.0, and Hashimoto/hypothyroidism and psoriasis = 1.4]. SIR for NHL diagnosis before age 60 (2.2) was significantly higher than that in older ages (age ≥60: 1.5). The SIRs in women or men and in period 1993–2010 or 1964–1992 were similar. Risk of all common NHL histology subtypes significantly increased after ADs (cutaneous/peripheral T cell and anaplastic large T and null cell = 2.2; small B-cell lymphocytic = 1.7; diffuse large B cell = 1.6; follicular and mantel cell = 1.3).ConclusionMany of 33 studied ADs (except for ankylosing spondylitis, diabetes type I graves/hyperthyroidism, multiple sclerosis, chorea minor, and pernicious anemia), especially when diagnosed at younger ages, were associated with higher risk of NHL. However, the absolute risk of NHL in many ADs is still small.     

Benzene exposure and risk of non-Hodgkin lymphoma.

Exposure to benzene, an important industrial chemical and component of gasoline, is a widely recognized cause of leukemia, but its association with non-Hodgkin lymphoma (NHL) is less clear. To clarify this issue, we undertook a systematic review of all case-control and cohort studies that identified probable occupational exposures to benzene and NHL morbidity or mortality. We identified 43 case-control studies of NHL outcomes that recognized persons with probable occupational exposure to benzene. Forty of these 43 (93%) studies show some elevation of NHL risk, with 23 of 43 (53%) studies finding statistically significant associations between NHL risk and probable benzene exposure. We also identified 26 studies of petroleum refinery workers reporting morbidity or mortality for lymphomas and all neoplasms and found that in 23 (88%), the rate of lymphoma morbidity or mortality was higher than that for all neoplasms. A substantial healthy-worker effect was evident in many of the studies and a comprehensive reevaluation of these studies with appropriate adjustments should be undertaken. Numerous studies have also reported associations between benzene exposure and the induction of lymphomas in mice. Further, because benzene is similar to alkylating drugs and radiation in producing leukemia, it is plausible that it might also produce lymphoma as they do and by similar mechanisms. Potential mechanisms include immunotoxicity and the induction of double-strand breaks with subsequent chromosome damage resulting in translocations and deletions. We conclude that, overall, the evidence supports an association between occupational benzene exposure and NHL.     

Alcohol intake and colorectal cancer risk by molecularly defined subtypes in a prospective study of older women

Increased alcohol consumption is a putative colorectal cancer (CRC) risk factor. However, existing data are less conclusive for women than men. Also, to date, relatively few studies have reported alcohol-related CRC risks based on molecularly defined tumor subtypes. We evaluated associations between alcohol intake and incident CRC, overall and by microsatellite instability [MSI high (MSI-H) or MSI low/microsatellite stable (MSI-L/MSS)], CpG island methylator phenotype (CIMP positive or CIMP negative), and BRAF mutation (mutated or wild-type) status in the prospective, population-based Iowa Women's Health Study (IWHS; n = 41,836). Subjects were 55 to 69 years at baseline (1986), and exposure data were obtained by self-report. Incident CRCs were prospectively identified and archived, paraffin-embedded tissue specimens were collected from 732 representative cases, diagnosed through December 31, 2002. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI). Among alcohol consumers, the median intake (range) was 3.4 (0.9-292.8) g/d. Compared with nonconsumers, alcohol intake levels of 3.4 g/d or less (RR = 1.00; 95% CI, 0.86-1.15) and more than 3.4 g/d (RR = 1.06; 95% CI, 0.91-1.24) were not significantly associated with overall CRC risk. Analyses based on alcohol intake levels of 30 g/d or less and more than 30 g/d or quartile distributions yielded similar risk estimates. Null associations were also observed between each alcohol intake level and the MSI-, CIMP- or, BRAF-defined CRC subtypes (P > 0.05 for each comparison). These data do not support an adverse effect from alcohol intake on CRC risk, overall or by specific molecularly defined subtypes, among older women.     

Occupation and the risk of non-Hodgkin lymphoma.

Although thus far no occupational agents have been classified as established causes of non-Hodgkin lymphoma (NHL), employment as a farmer, teacher, dry cleaner, meat worker, printer, or wood worker has been associated with elevated risk in the peer-reviewed literature. We conducted several meta-analyses to assess risk in these occupations and industries from articles published in MEDLINE up to August 1, 2006. The summary risk estimates suggest a homogeneous excess risk for NHL among workers in the printing industry [relative risk (RR), 1.86; 95% confidence interval (95% CI), 1.37-2.52] and wood workers (RR, 1.15; 95% CI, 1.00-1.31). Considerable heterogeneity but elevated risks were found for farmers (RR, 1.11; 95% CI, 1.05-1.17), especially in animal husbandry (RR, 1.31; 95% CI, 1.08-1.60), and teaching (RR, 1.47; 95% CI, 1.34-1.61). An increased risk was absent for employment in the meat processing industry (RR, 0.99; 95% CI, 0.77-1.29). These results suggest that although excess risk is found for employment in the printing industry, wood processing industry, teaching, and farming, it is unlikely that occupation represents a major risk factor for NHL in most populations. At present, no conclusive evidence of causal relations between occupations and increased NHL risk exists; this can be ascribed to methodologic problems in studying the link between NHL risk and occupation, including heterogeneity of disease and exposure circumstances and low statistical power. Implementing state-of-the-art exposure assessment technologies, including biomarker-based assessment, and aiming to identify susceptible subgroups can increase the statistical power enough to analyze etiologically relevant NHL subtypes and provide clues on possible causal agents in future studies. These goals can be best attained within the framework of large-scale, international collaborative projects.