non-Hodgkin's Lymphoma In Men Research Articles

Cancer incidence in agricultural cohorts

TPS 791: Occupational health 1, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background/Aim. An international consortium of agricultural cohort studies, AGRICOH, was established to study cancer and other health outcomes in relation to agricultural exposures. The present analysis aimed to compare the cancer incidence rates between AGRICOH cohorts and the general population. Methods. The analysis included eight AGRICOH cohorts from six different countries. These cohorts varied in size and types of workers included: active and retired agricultural workers, farm owners, and pesticide applicators. From each cohort, information on primary incident cancers (excluding non-melanoma skin cancer), person-years of follow-up, and national/regional cancer rates was obtained. With this information, cohort- and sex-specific standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated for each cancer site and all cancers combined. Random effects meta-analysis of SIR was then performed when five or more cases were observed in at least four (women) or five (men) of the cohorts. Results. During >3,000,000 person-years, 26,054 cancers were diagnosed. Overall, the meta-SIR was 0.70 (95% CI=0.57-0.84) in women and 0.74 (95% CI=0.66-0.82) in men. A lower incidence rate was observed for cancers of breast (meta-SIR=0.67, 95% CI=0.47-0.86), colorectum (meta-SIR=0.80, 95% CI=0.61-0.99), and lung (meta-SIR=0.68, 95% CI=0.43-0.92) in women and for cancers of bladder (meta-SIR=0.54, 95% CI=0.39-0.68), larynx (meta-SIR=0.49, 95% CI=0.41-0.57), lung (meta-SIR=0.54, 95% CI=0.41-0.68), oesophagus (meta-SIR=0.62, 95% CI=0.44-0.81), and pancreas (meta-SIR=0.73, 95% CI=0.65-0.81) in men as compared to the general population. Non-significantly increased meta-SIRs were found for melanoma in women (meta-SIR=1.19, 95% CI=0.67-1.72) and non-Hodgkin lymphoma in men (meta-SIR=1.19, 95% CI=0.78-1.60). Conclusions. The overall cancer incidence rate was lower in AGRICOH than in the general population. The observed lower cancer incidence may be due to healthy worker bias, lower prevalence of risk factors, such as smoking in the agricultural populations, or other reasons. Further analysis is underway to explore any heterogeneity in SIR of cancer across cohorts.

Longitude Position in a Time Zone and Cancer Risk in the United States.

Background: Circadian disruption is a probable human carcinogen. From the eastern to western border of a time zone, social time is equal, whereas solar time is progressively delayed, producing increased discrepancies between individuals' social and biological circadian time. Accordingly, western time zone residents experience greater circadian disruption and may be at an increased risk of cancer.Methods: We examined associations between the position in a time zone and age-standardized county-level incidence rates for total cancers combined and 23 specific cancers by gender using the data of the Surveillance, Epidemiology, and End Results Program (2000-2012), including four million cancer diagnoses in white residents of 607 counties in 11 U.S. states. Log-linear regression was conducted, adjusting for latitude, poverty, cigarette smoking, and state. Bonferroni-corrected P values were used as the significance criteria.Results: Risk increased from east to west within a time zone for total and for many specific cancers, including chronic lymphocytic leukemia (both genders) and cancers of the stomach, liver, prostate, and non-Hodgkin lymphoma in men and cancers of the esophagus, colorectum, lung, breast, and corpus uteri in women.Conclusions: Risk increased from the east to the west in a time zone for total and many specific cancers, in accord with the circadian disruption hypothesis. Replications in analytic epidemiologic studies are warranted.Impact: Our findings suggest that circadian disruption may not be a rare phenomenon affecting only shift workers, but is widespread in the general population with broader implications for public health than generally appreciated. Cancer Epidemiol Biomarkers Prev; 26(8); 1306-11. ©2017 AACR.

Systematic review of the relationship between artificial sweetener consumption and cancer in humans: analysis of 599,741 participants.

The effect of artificial sweetener consumption on cancer risk has been debated in animal models for over four decades. To further investigate this relationship, this study aims to synthesise results from several of the most recent studies in humans. An online literature search was performed in MEDLINE from 2003 to 2014 using Ovid, PubMed, Web of Science, and Scopus using keywords 'artificial', 'sweetener' and 'cancer'. Ninety-two results were then manually assessed for eligibility. Studies were included if the relationship between artificial sweeteners and cancer was their central hypothesis, and if they adjusted for age, gender, smoking status and body mass index. Extracted data included study design, patient characteristics, outcome measure and results. In the five publications that satisfied the inclusion criteria, significant direct associations with artificial consumption were found for laryngeal (odds ratio, OR 2.34, 95% CI: 1.20-4.55), urinary tract tumours (OR 2.12, 95% CI: 1.22-3.89), non-Hodgkin lymphoma in men (RR 1.31, 95% CI: 1.01-1.72), multiple myeloma in men (RR 2.02, 95% CI: 1.20-3.40) and leukaemia (RR 1.42, 95% CI: 1.00-2.02). Inverse relationships were found in breast (OR 0.70, 95% CI: 0.54-0.91, p trend = 0.015) and ovarian (OR 0.56, 95% CI: 0.38-0.81, p trend < 0.001) cancers. The statistical value of this review is limited by the heterogeneity and observational designs of the included studies. Although there is limited evidence to suggest that heavy consumption may increase the risk of certain cancers, overall the data presented are inconclusive as to any relationship between artificial sweeteners and cancer.

Abstract A73: Body mass index, diet, and risk of non-Hodgkin lymphoma in the Nurses' Health Study and Health Professionals Follow-Up Study

Abstract Background: The etiology of non-Hodgkin lymphoma (NHL) is poorly understood, especially regarding modifiable risk factors that could inform prevention messages. Obesity and diet are potentially modifiable risk factors that may contribute to lymphomagenesis by influencing inflammation or carcinogen exposure. Prospective data on obesity, diet, and NHL risk are limited and inconsistent. After 14 years of follow-up in the Nurses' Health Study (NHS), we observed significant associations of fat and vegetable intake with NHL risk. We expanded these analyses to further examine the roles of obesity and diet in NHL etiology in the NHS and Health Professionals Follow-up Study (HPFS) cohorts after substantially longer follow-up. Methods: The NHS was established in 1976, when 121,700 female nurses aged 30–55 years completed a self-administered questionnaire on lifestyle behaviors and medical history. The HPFS comprises 51,529 male dentists and other health professionals aged 40–75 years at baseline in 1986. Biennial questionnaires are sent to participants to update risk factor information and identify new diagnoses and have included a validated semiquantitative food frequency questionnaire (FFQ) to assess diet every 2 to 4 years since 1980 in the NHS and 1986 in the HPFS. The present analyses included 91,227 women who completed the 1980 NHS-FFQ and 47,542 men who completed the 1986 HPFS-FFQ and had no prior history of cancer. We confirmed 966 incident diagnoses of NHL among women through 2008 and 566 cases among men through 2006. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for risk of NHL associated with current and young adult (NHS, age 18; HPFS, age 21) body mass index (BMI) and selected dietary factors (i.e., total fat, animal fat, vegetable fat, saturated fat, trans fat, fruits, and vegetables). We examined updated cumulative average food and energy-adjusted nutrient intakes. Multivariable models controlled for potential confounding by age, race, BMI, height, smoking history, physical activity, and total energy intake. Results: Young adult BMI was positively associated with NHL risk in both women (p-trend=0.02) and men (p-trend=0.002) in multivariable models. Women with BMI ≥30 kg/m2 at age 18 (vs. &amp;lt;21 kg/m2) had a 19% higher risk of NHL (HR: 1.19; 95% CI: 0.74–1.91). Men with BMI ≥30 kg/m2 at age 21 (vs. &amp;lt;23 kg/m2) had a 63% higher NHL risk (HR: 1.63; 95% CI: 0.92–2.88). Current BMI was also associated with NHL in men (HRBMI ≥30: 1.48; 95% CI: 1.05–2.09) but not in women (HRBMI ≥30: 0.88; 95% CI: 0.70, 1.12). Neither total nor specific dietary fats were significantly associated with NHL; however, women in the top quintile (Q5) of trans fat intake (vs. Q1) had a non-significantly increased NHL risk (HR: 1.19; 95% CI: 0.95–1.51). Men and women who consumed ≥4 servings of vegetables/day (vs. &amp;lt;2 servings/day) had a slightly lower risk of NHL (HRmen: 0.87, 95% CI: 0.67–1.13; HRwomen: 0.84, 95% CI: 0.67–1.04). Total fruit intake was not associated with NHL. Conclusions: These preliminary analyses in two large prospective cohorts support the hypothesis that obesity in young adulthood predicts increased risk of all NHL in both men and women. We also observed a suggested positive association of NHL risk with trans fat intake in women and a modest inverse association with vegetable intake in men and women, consistent with our earlier reports. It is plausible that there is etiologic heterogeneity across the &amp;gt;30 NHL histologic subtypes. Ongoing analyses to examine the relationship of obesity and diet with major NHL histologic subtypes in the NHS and HPFS may yield further insights into their roles in NHL etiology and prevention. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A73.

Exposure to multiple pesticides and risk of non-Hodgkin lymphoma in men from six Canadian provinces.

Non-Hodgkin lymphoma (NHL) has been linked to several agricultural exposures, including some commonly used pesticides. Although there is a significant body of literature examining the effects of exposure to individual pesticides on NHL, the impact of exposure to multiple pesticides or specific pesticide combinations has not been explored in depth. Data from a six-province Canadian case-control study conducted between 1991 and 1994 were analyzed to investigate the relationship between NHL, the total number of pesticides used and some common pesticide combinations. Cases (n = 513) were identified through hospital records and provincial cancer registries and controls (n = 1,506), frequency matched to cases by age and province of residence, were obtained through provincial health records, telephone listings, or voter lists. In multiple logistic regression analyses, risk of NHL increased with the number of pesticides used. Similar results were obtained in analyses restricted to herbicides, insecticides and several pesticide classes. Odds ratios increased further when only ‘potentially carcinogenic’ pesticides were considered (OR[one pesticide] = 1.30, 95% CI = 0.90–1.88; OR[two to four] = 1.54, CI = 1.11–2.12; OR[five or more] = 1.94, CI = 1.17–3.23). Elevated risks were also found among those reporting use of malathion in combination with several other pesticides. These analyses support and extend previous findings that the risk of NHL increases with the number of pesticides used and some pesticide combinations.

Mutations In Circadian Rhythm Genes Are Associated with Diffuse Large B-Cell Lymphoma In the Mexican Population

AbstractAbstract 2478In Mexico, diffuse large B-cell lymphoma (DLBCL) is the most common histological non-Hodgkin's lymphoma (NHL) subtype and is observed in up to 48% of all diagnoses of lymphoma. It has recently been hypothesized that circadian disruption may have a connection with lymphomagenesis. The circadian clock maintains biological rhythms over a cycle of approximately 24 hours, and many physiological functions in the human body are regulated by this system. The disruption of the circadian cycle may negatively affect cellular function, potentially leading to increased susceptibility to certain malignancies. Evidence in support of this association has been provided by epidemiological studies that demonstrate that night-time work significantly increased the risk of NHL in men, the overall relative risk being 1.10 (95%CI = 1.03–1.19, p = 0.010)(Lahti et al., Int J Cancer 2008). The study was performed to determinate if functional single nucleotide polymorphisms (SNP) in circadian rhythm genes are associated with the presence of DLBCL in Mexican patients. A molecular mechanism to regulate the circadian rhythm has been identified, where nine genes have been involved: clock, npas2, bmal1, per1-3, cry1-2, and csnk1e. Recent studies have shown that approximately 10% of genes exhibit circadian patterns of expression in a given tissue, and 10% of these clock-controlled genes identified regulate either cell proliferation or apoptosis. For this current study, SNPs were evaluated in DNA samples isolated from histopathologically-confirmed DLBCL patients (N=30) and healthy volunteers (N=50) as a control population. Samples were provided by Hospital Regional de Especialidades IMSS No. 25 and Hospital Metropolitano, in Monterrey, Nuevo Leon, Mexico. The selection of functional SNPs was made using a bioinformatic tool called Function Analysis and Selection Tool for Single Nucleotide Polymorphisms (FASTSNP)(Yuan et al., Nucl. Acids Res 2006). Six genes that regulate the circadian rhythm were submitted to FASTSNP, and 13 high-risk SNPs were used for this study. The results provided were npas2 rs11541353, per1 rs3027189, rs3027180, and rs3027177; per2 rs2340885, and rs3739068; per3 rs228697, rs2640905, rs12078704, and rs57875989; tim rs2291739, and rs2638290; and cry2 rs2863712. Primers were designed for the 13 high-risk SNPs. The SNPs were amplified by PCR in a 96-well plate. Alleles were determined by presence of the resultant bands in an agarose gel electrophoresis. SNPs analysis showed that DLBCL patients were mutated in 93.3% (28/30), while the population of controls were only in 74.0% (37/50) who presented with mutations (p = 0.023). The rs2291739 variant of the tim gene was the most frequent homozygous mutant found in at least 50% of both controls and patients. Two SNPs were found to be statistically significant associated with DLBCL, these were per1 rs3027189 (p = 0.006) and cry2 rs2863712 (p = 0.002). The per1 gene plays an important role in regulating growth and DNA damage control and also interacts with proteins in the cell-cycle pathway. CRY2 has been shown to alter genes associated with immune response and hematological system development. These results suggest that these two genes might play an important role in influencing biological pathways relevant for lymphomagenesis. These findings contribute in part to the recent research that links the disruption of circadian rhythm with the processes of lymphomagenesis. Further studies are warranted. This study was supported by Catedra de Hematologia y Cancer from Tecnologico de Monterrey. Disclosures:No relevant conflicts of interest to declare.

Plasma Organochlorine Levels and Risk of Non-Hodgkin Lymphoma in the Physiciansʼ Health Study

ISEE-0522 Background and Objective: Non-occupational exposure to polychlorinated biphenyls (PCBs) and p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) may increase the risk of non-Hodgkin lymphoma (NHL). Methods: We conducted a case-control study nested within the Physicians' Health Study, a prospective cohort established in 1982. We measured concentrations of PCBs and p,p′-DDE in baseline blood samples from 205 men diagnosed with NHL and 409 age- and race-matched controls. Lipid-adjusted organochlorine concentrations were categorized into quintiles based on the distribution among controls. We used conditional logistic regression to estimate the rate ratios (RRs) and 95% confidence intervals (CIs) for each quintile relative to the lowest quintile. We also evaluated these associations for major histologic subtypes of NHL. Results: We found significant positive associations for the sum of 51 PCB congeners assayed (ΣPCB), the group of immunotoxic congeners, the individual congeners 118, 138, 153, and 180, and the sum of these four congeners with risk of NHL. The simple RR for the highest quintile of lipid-adjusted ΣPCB versus the lowest was 1.9 (95% CI: 1.1–3.2; P -trend = 0.001), with similar trends for individual congeners and groups defined as above. Adjustment for height, body mass index, alcohol intake, smoking, and fish intake did not substantially change the effect estimates. No association was observed for p,p′-DDE. There was no evidence of statistical heterogeneity in effects by histologic subtype. Conclusions: These results support the hypothesis of a positive association between PCB exposure and development of NHL in men.

Does HIV/AIDS Have a Biological Impact on the Risk of Human Papillomavirus–Related Cancers?

HIV-related immunosuppression is a well-accepted, strong biological risk factor for two virus-associated cancers: Kaposi’s sarcoma, which is associated with Kaposi’s sarcoma – associated herpesvirus, and non-Hodgkin lymphoma, which is associated with Epstein – Barr virus. In fact, recognition of an extraordinarily high rate of Kaposi’s sarcoma among men who have sex with men in New York and California during the early 1980s was one of the first indications of the existence of a human immunodeficiency virus ( 1 – 3 ). Soon thereafter, high rates of non-Hodgkin lymphoma in men who have sex with men were also recognized ( 4 , 5 ), and both Kaposi’s sarcoma and non-Hodgkin lymphoma became designated as AIDS-defining malignancies in HIV-positive patients ( 6 – 8 ). It was not until the 1990s though that formal linkages between population-based AIDS registries and cancer registries were initiated ( 9 , 10 ). The AIDS – cancer match registry study in the United States ( 11 , 12 ), and similar studies in other countries ( 13 – 15 ), found that the risks for both Kaposi’s sarcoma and non-Hodgkin lymphoma were increased by at least 100-fold in persons who developed AIDS compared with the general population ( 11 , 12 ). Furthermore, there were indications of a biological gradient—one of several criteria used to assess a possible causal relationship. Specifically, the risks for both Kaposi’s sarcoma and non-Hodgkin lymphoma increased, and with lower CD4 T-cell count at time of AIDS onset ( 16 ) with increasing time after AIDS diagnosis (which is thought to be a surrogate indicator

Night‐time work predisposes to non‐Hodgkin lymphoma

Our aim was to find out whether non-Hodgkin lymphoma (NHL) was more common than expected among night-time shift workers. The Finnish job-exposure matrix (FINJEM) provided estimates of the proportion of exposed persons and the mean level of exposure among the exposed in each occupation. The probability of night-time work in each occupation was assessed, the observed and expected numbers of cancer cases in a cohort of persons born in 1906-1945 during the years of 1971-1995 were calculated, and the cumulative index of night-time work was scored. The cohort compromised of 1,669,272 persons of whom 6,307 (3,813 men and 2,494 women) had NHL during the follow-up. Night-time work increased significantly (p = 0.01) the risk of NHL in men, the overall relative risk being 1.10 (95% confidence interval of 1.03-1.19). Using the lag period of 10 years, the risk ratio was 1.28 (1.03-1.59) for men who worked in night-time shifts to a high degree as compared with those who had not been exposed to night-time work. Night-time workers are cancer prone and have a greater risk of NHL than population on average.

Overweight and Obesity at Different Times in Life as Risk Factors for Non-Hodgkin's Lymphoma: The Multiethnic Cohort

Obesity may increase the risk for non-Hodgkin's lymphoma (NHL) through an inflammatory pathway. We explored the relation of NHL with body size at different times in life within the Multiethnic Cohort that includes African Americans, Caucasians, Japanese, Latinos, and Native Hawaiians. Participants were 45 to 75 years old at recruitment in 1993 to 1996. This analysis included 87,079 men and 105,972 women with 461 male and 378 female NHL cases. We used Cox regression to model NHL risk with age as the time metric while adjusting for age at baseline, ethnicity, education, alcohol intake, and age at first live birth. Body weight and body mass index at age 21 were stronger predictors of NHL risk than anthropometric characteristics at baseline. For men, being in the highest quartile of body mass index and body weight at age 21 conferred a nonsignificant 86% and 41% higher NHL risk, respectively, whereas there was no association at baseline. For women, the risk associated with the highest quartile of weight at age 21 was 1.6 (P(trend) = 0.04), whereas women in the highest quartile at baseline had a nonsignificant risk of 27%. Height was positively related to NHL in men and women. Despite the small numbers, there was some consistency for risk estimates across ethnic groups and weak evidence for an association with NHL subtypes. These findings indicate that weight at age 21 may represent lifetime adiposity better than body weight at cohort entry. Alternatively, weight at age 21 may be more relevant for the etiology of NHL.

Dietary Factors and Risk of Non-Hodgkin Lymphoma in Men and Women

The incidence of non-Hodgkin lymphoma (NHL) has increased worldwide in recent decades. Diet could influence NHL risk by modulating the immune system, although evidence is limited. We did a population-based case-control study to determine whether differences in diet were associated with NHL risk. A total of 597 NHL cases and 467 population controls in Sweden completed a semiquantitative food frequency questionnaire evaluating their dietary habits 2 years before the interview. Unconditional logistic regression was used to estimate the odds ratios (OR) and corresponding 95% confidence intervals (95% CI) for associations between food intake and risk of NHL. High consumption of dairy products and fried red meat was associated with increased risk of NHL. The OR of NHL for individuals in the highest quartile compared with the lowest quartile of dairy intake was 1.5 (95% CI, 1.1-2.2; P(trend) = 0.003). The OR for the highest versus lowest quartile of fried red meat intake was 1.5 (95% CI, 1.0-2.1; P(trend) = 0.02). In contrast, high consumption of fruits and vegetables was associated with reduced risk of NHL, particularly follicular lymphoma, among women but not men. Compared with the lowest quartile of vegetable intake, the OR of follicular lymphoma among women in the highest quartile of vegetable intake was 0.3 (95% CI, 0.1-0.7; P(trend) = 0.002). The positive associations of NHL risk with dairy products and fried red meat and the inverse association with fruits and vegetables suggest that diet affects NHL risk and could explain the increase of some histopathogic subtypes.

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

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. 613 NHL cases and 480 population controls in Sweden reported their average consumption of beer, wine, and liquor 2 years 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. 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 19.1 g of ethanol per day, compared to those who consumed on average 0-2.2 g of ethanol per day (OR = 1.2 (95% CI: 0.8, 1.7); Ptrend = 0.29). However, the association was significantly positive among males (OR = 1.8 (95% CI: 1.1, 2.9); Ptrend = 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. Alcohol does not appear to be a major etiologic factor for overall NHL, nor its common subtypes.

Alcohol Consumption, Family History of Hematolymphoproliferative Cancer, and the Risk of Non-Hodgkin's Lymphoma in Men

PURPOSE: To investigate the association between alcohol consumption and the risk of non-Hodgkin's lymphoma (NHL) and to examine whether the association is modified by a family history of hematolymphoproliferative cancer (HLPC). METHODS: Data on white men from two population-based case-control studies of NHL conducted in Iowa/Minnesota and Kansas were pooled for this analysis. Information on alcohol consumption, family history of HLPC, and other factors was obtained by interviewing 792 cases and 2193 controls or, if deceased, their next-of-kin. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: There was no clear association between NHL and the use of alcohol, beer, hard liquor, or wine. The relationship, however, may differ according to a family history of HLPC. Alcohol use was not associated with the risk of NHL in men without a family history of HLPC (ORs = 0.8 and 0.9 for men consuming alcohol ⩽ median and > median, respectively), the presence of a family history in the absence of alcohol use was associated with a slightly increased risk (OR = 1.4; 95% CI 0.8–2.5), whereas risks of NHL among men with a positive family history were 2.1 (CI 1.0–4.7) for men consuming alcohol ⩽ median (13.7 g/day) and 2.8 (1.3–5.9) for men consuming alcohol greater than median. CONCLUSIONS: The present data found no clear association between alcohol consumption and the risk of NHL among men without a family history of HLPC, whereas alcohol intake was associated an elevated risk in men with a positive family history. The finding of effect modification of the alcohol-NHL association by a family history of HLPC is novel and requires confirmation.

Alcohol, tobacco and recreational drug use and the risk of non-Hodgkin's lymphoma.

A population based case-control study was conducted to determine whether risk of non-Hodgkin's lymphoma (NHL) in the absence of HIV infection is related to the previous use of tobacco, alcohol or recreational drugs. A total of 378 residents of Los Angeles County who were diagnosed with high- or intermediate-grade NHL were compared with individually age-, race- and sex-matched neighbourhood control subjects with regard to history of use of tobacco products, alcohol and ten specific recreational drugs. Risk of NHL among women decreased with increased consumption of alcoholic beverages (trend P = 0.03), with risk 50% lower among those consuming five or more drinks per week than among non-drinkers. Cocaine, amphetamines, Quaaludes and lysergic acid diethylamide (LSD) were each associated with a significantly increased risk of NHL in men with risk greater among those with more frequent use of these drugs. Confounding factors could not be excluded in these findings. The use of multiple types of drugs was also associated with a significantly increased risk of NHL in men (trend P = 0.005) with risk greatest among those using five or more types of drugs (odds ratio = 5.8, 95% confidence limits = 1.2-28.4); among these drugs, cocaine use appeared to account for the elevated risk of NHL among men based on multivariable analyses.