Obesity and the risk of gallbladder cancer: a meta-analysis

We performed a meta-analysis of studies of the association between excess body weight and risk of gallbladder cancer identified from MEDLINE and EMBASE databases from 1966 to February 2007 and the references of retrieved articles. A random-effects model was used to combine results from eight cohort studies and three case-control studies, with a total of 3288 cases. Compared with individuals of 'normal weight', the summary relative risk of gallbladder cancer for those who were overweight or obese was 1.15 (95% CI, 1.01-1.30) and 1.66 (95% CI, 1.47-1.88) respectively. The association with obesity was stronger for women (relative risk, 1.88; 95% CI, 1.66-2.13) than for men (relative risk, 1.35; 95% CI, 1.09-1.68). There was no statistically significant heterogeneity among the results of individual studies. This meta-analysis confirms the association between excess body weight and risk of gallbladder cancer.     

Body mass index and pancreatic cancer risk: A meta-analysis of prospective studies

A number of studies have examined the association between body mass index (BMI) and risk of pancreatic cancer, but uncertainty about the relationship remains. We performed a meta-analysis to summarize the evidence from prospective studies investigating this association. We searched MEDLINE for studies published in any language from 1966 to November 2006. Prospective studies were included if they reported relative risks (RRs) with 95% confidence intervals (CIs) for the association between BMI and pancreatic cancer incidence or mortality. Study-specific RR estimates were combined by use of a random-effects model. A total of 21 independent prospective studies, involving 3,495,981 individuals and 8,062 pancreatic cancer cases, met the inclusion criteria. The estimated summary RR of pancreatic cancer per 5 kg/m(2) increase in BMI was 1.12 (95% CI, 1.06-1.17; p-heterogeneity = 0.13) in men and women combined, 1.16 (95% CI, 1.05-1.28; p-heterogeneity = 0.001) in men, and 1.10 (95% CI, 1.02-1.19; p-heterogeneity = 0.12) in women. There was no evidence of publication bias (p = 0.58). Findings from this meta-analysis of prospective studies support a positive association between BMI and risk of pancreatic cancer in men and women.     

Asthma history, occupational exposure to pesticides and the risk of non-Hodgkin's lymphoma

We previously reported that, although asthma did not increase the risk of non-Hodgkin's lymphoma (NHL), the risk from pesticide exposures was higher among asthmatics than that among nonasthmatics. To further evaluate this finding, we analyzed data from a population-based case-control study of NHL conducted in Iowa, Detroit, Los Angeles and Seattle. Cases (n = 668) diagnosed with NHL from 1998 to 2000 and controls (n = 543) randomly selected from the same geographical areas as that of the cases were included in this analysis. Odds ratios (OR) for the risk of NHL from potential occupational exposure to pesticides tended to be higher among asthmatics (OR = 1.7; 95% CI 0.3-9.1) when compared with that among nonasthmatics (OR = 0.9; 95% CI 0.6-1.5). The risks of NHL associated with pesticide exposure were also higher among asthmatics who had history of hospitalization (OR = 2.1; 95% CI 0.2-29.0) or daily medication for asthma (OR = infinite) than those among asthmatics who did not have such histories. Our results support the previous finding that the risk of NHL from pesticide exposure may be greater among asthmatics.     

Body mass index and risk of multiple myeloma: a meta-analysis

Excess body weight has been identified as a risk factor for a variety of cancer types. However, whether excess body weight increases the risk of multiple myeloma remains controversial. We conducted a meta-analysis to quantitatively summarize the evidence from epidemiologic studies of the associations of overweight and obesity with the risk of multiple myeloma. We searched the MEDLINE and EMBASE databases (1966 to May 2007) and the reference lists of retrieved articles. Cohort and case-control studies were included if they reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the relation between body mass index and multiple myeloma incidence or mortality. A random-effects model was used to combine study-specific results. A total of 11 cohort studies (involving 13,120 cases) and 4 case-control studies (1,166 cases and 8,247 controls) were included in the meta-analysis. Compared with individuals with normal weight, the risk of multiple myeloma was statistically significantly higher among those who were overweight (cohort studies: RR, 1.12, 95% CI, 1.07-1.18; case-control studies: RR, 1.43; 95% CI, 1.23-1.68) or obese (cohort studies: RR, 1.27, 95% CI, 1.15-1.41; case- control studies: RR, 1.82, 95% CI, 1.47-2.26). Results from this meta-analysis indicate that excess body weight may be a risk factor for multiple myeloma.     

History of antibiotic use and risk of non-Hodgkin's lymphoma (NHL)

A population-based, incidence case-control study was conducted among women in upstate New York to determine whether histories of certain infections and antibiotic use are associated with risk of non-Hodgkin's lymphoma (NHL). Our study involved 376 cases of NHL identified through the New York State Cancer Registry and 463 controls selected from the Medicare beneficiary files and state driver's license records. Information about use of common medications including antibiotics, history of selected infectious diseases and potential confounding variables was obtained by telephone interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using an unconditional logistic regression model. There was a progressive increase in risk of NHL with increasing frequency and duration of systemic antibiotic use, as assessed over the period of 2-20 years before the interview. The ORs for the highest exposure categories, >/=36 episodes and >/=366 days of use, were 2.56 (95% CI 1.33-4.94) and 2.66 (95% CI 1.35-5.27), respectively. These associations were primarily due to antibiotic use against respiratory infections and dental conditions. Moreover, the association with frequency of antibiotic use for respiratory infections was pronounced for marginal zone B-cell lymphoma and for respiratory tract lymphoma. Analyses by class of antibiotics did not suggest that a general cytotoxic effect of antibiotics was responsible for these increased risks. Although recall bias and selection bias remain potential concerns in our study, the results are generally consistent with the hypothesis that persistent infection/inflammation predisposes individuals to the development of NHL. However, a direct role of antibiotics in NHL induction has not been ruled out.     

Overweight and obesity and incidence of leukemia: a meta-analysis of cohort studies

We conducted a meta-analysis to summarize the available evidence from cohort studies on the association between excess body weight and incidence of leukemia. Studies were identified by searching the MEDLINE and EMBASE databases (1966-July 2007) and by examining the references of retrieved articles. A random-effects model was used to combine the results from individual studies. We identified 9 cohort studies with data on body mass index (BMI) or obesity in relation to incidence of leukemia. Compared with nonoverweight individuals (BMI < 25 kg/m(2)), the summary relative risks (RRs) of leukemia were 1.14 [95% confidence interval (CI), 1.03-1.25] for overweight individuals (BMI 25-30 kg/m(2)) and 1.39 (95% CI, 1.25-1.54) for obese (BMI >or= 30 kg/m(2)) individuals. On a continuous scale, a 5 kg/m(2) increase in BMI was associated with a 13% increased risk of leukemia (RR, 1.13; 95% CI, 1.07-1.19). In a meta-analysis of 4 studies reporting results on subtypes of leukemia, the summary RRs associated with obesity were 1.25 (95% CI, 1.11-1.41) for chronic lymphocytic leukemia, 1.65 (95% CI, 1.16-2.35) for acute lymphocytic leukemia, 1.52 (95% CI, 1.19-1.95) for acute myeloid leukemia and 1.26 (95% CI, 1.09-1.46) for chronic myeloid leukemia. This meta-analysis indicates that excess body weight is associated with an increased risk of developing leukemia.     

Antioxidant intake from fruits,vegetables and other sources and risk of non‐Hodgkin's lymphoma: the Iowa Women's Health Study

Antioxidant nutrients found in fruits, vegetables and other foods are thought to inhibit carcinogenesis and to influence immune status. We evaluated the association of these factors with risk of non‐Hodgkin's lymphoma (NHL) overall and for diffuse large B‐cell lymphoma (DLBCL) and follicular lymphoma specifically in a prospective cohort of 35,159 Iowa women aged 55–69 years when enrolled at baseline in 1986. Diet was ascertained using a validated semiquantitative food frequency questionnaire. Through 2005, 415 cases of NHL (including 184 DLBCL and 90 follicular) were identified. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox regression, adjusting for age and total energy. The strongest associations of antioxidants with risk of NHL (RR for highest versus lowest quartile; p for trend) were observed for dietary vitamin C (RR = 0.78; p = 0.044), α‐carotene (RR = 0.71; p = 0.015), proanthocyanidins (RR = 0.70; p = 0.0024) and dietary manganese (RR = 0.62; p = 0.010). There were no associations with multivitamin use or supplemental intake of vitamins C, E, selenium, zinc, copper or manganese. From a food perspective, greater intake of total fruits and vegetables (RR = 0.69; p = 0.011), yellow/orange (RR = 0.72; p = 0.015) and cruciferous (RR = 0.82; p = 0.017) vegetables, broccoli (RR = 0.72; p = 0.018) and apple juice/cider (RR = 0.65; p = 0.026) were associated with lower NHL risk; there were no strong associations for other antioxidant‐rich foods, including whole grains, chocolate, tea or nuts. Overall, these associations were mainly observed for follicular lymphoma and were weaker or not apparent for DLBCL. In conclusion, these results support a role for vegetables, and perhaps fruits and associated antioxidants from food sources, as protective factors against the development of NHL and follicular lymphoma in particular.     

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.     

Hepatitis C infection is not associated with systemic HIV-associated non-Hodgkin's lymphoma: a cohort study

Immunosuppression induced by the human immunodeficiency virus (HIV) increases the risk of developing non-Hodgkin's lymphoma (NHL). As the hepatitis C virus (HCV) has been implicated in the development of B cell lymphomas, we compared the incidence of systemic NHL during HIV infection compared to HIV and HCV co-infection. Of 5,832 individuals studied during the era of highly active anti-retroviral therapy (HAART), 102 patients were diagnosed with systemic NHL. The incidence of systemic NHL was 6.9 of 10(4) patient years during HIV infection compared to 7.1 of 10(4) patient years during HIV alone (p = 0.9). In this immunocompromised patient population, there was no association between HCV infection and an increased risk of lymphoma.     

Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies

Cohort studies of excess body weight and risk of liver cancer were identified for a meta-analysis by searching MEDLINE and EMBASE databases from 1966 to June 2007 and the reference lists of retrieved articles. Results from individual studies were combined using a random-effects model. We identified 11 cohort studies, of which seven on overweight (with a total of 5037 cases) and 10 on obesity (with 6042 cases) were suitable for meta-analysis. Compared with persons of normal weight, the summary relative risks of liver cancer were 1.17 (95% confidence interval (CI): 1.02-1.34) for those who were overweight and 1.89 (95% CI: 1.51-2.36) for those who were obese. This meta-analysis finds that excess body weight is associated with an increased risk of liver cancer.     

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

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

Critical review of epidemiological studies of the association between smoking and non-Hodgkin's lymphoma.

Smoking has been suggested to increase the risk of non-Hodgkin's lymphoma (NHL) but the results of epidemiological studies have been inconsistent. The aim of this work was to assess whether the findings of individual studies might have arisen by chance, bias or confounding and whether any associations found between smoking and NHL represent cause-and-effect. Reports of the association between smoking and NHL were identified from Medline. Confidence intervals on relative risks and odds ratios, use of multiple comparisons, and information on source, direction, actual existence and size of potential biases and confounding and features of any associations were abstracted. Four out of five cohort studies found no association between current smoking and NHL but three may have been biased against doing so. One found an association with follicular lymphoma but without a convincing exposure-risk gradient. The fifth found a strong association and an exposure-response gradient with ever smoking but excluded living cases from the end-point. Only one study found an association with past smoking which lacked features of causality. Eight out of 14 case-control studies found no association between current and/or past smoking and NHL but five may have been biased against doing so. Of six positive studies, three involved multiple comparisons, the association of one became non-significant after eliminating bias, four did not explore features of causality and one found an association only in heavy smokers, particularly under 45 years old. There are no grounds to reject the null hypothesis but associations should continue to be sought particularly in subgroups of smokers and with NHL subtypes.     

Ophthalmologic and intraocular non-Hodgkin's lymphoma: a large single centre study of initial characteristics, natural history, and prognostic factors

The aims of this study were to define the initial characteristics, natural history, and prognostic factors of patients with ophthalmologic and intraocular malignant lymphoma. All patients treated at the Institut Curie for lymphoma with ophthalmologic (orbit and/or adnexa) or intraocular involvement were retrospectively reviewed. A pathological review of all cases was performed according to the WHO classification. One hundred and forty-five patients were selected for the study. Pathological review showed 36% MALT type lymphoma, 22% lymphoplasmocytic lymphoma, and 15% diffuse large B-cell lymphoma. Ophthalmologic and ocular sites were intra-orbital in 61 cases (42%) and conjunctival in 51 cases (35%), with bilateral involvement in 10% of cases. Stage IV was found in 32% of cases, with bone marrow involvement in 12%. With a median follow-up of 90 months, the 5-year DFS and OS were 64 and 79% for low-grade NHL, and 43 and 50% for high-grade NHL. On multivariate analysis, age greater than 59 years, elevated LDH level, stage IV, high-grade histological subgroup, and presence of B-symptoms had a negative impact on OS for the overall population. In conclusion, with a median follow-up of 7.5 years, our large cohort of patients represents one of the largest published series on primary ophthalmologic and intraocular malignant lymphoma.     

Childhood Hodgkin's lymphoma, non-Hodgkin's lymphoma and factors related to the immune system: the Escale Study (SFCE)

The study investigated the role of factors considered related to the early stimulation of the immune system in the aetiology of childhood lymphoma. The national registry-based case-control study, Escale, was carried out in France over the period 2003-2004. Population controls were frequency matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders. Data from 128 cases of Hodgkin's lymphoma (HL) aged 5-14 years, 164 cases of non-Hodgkin's lymphoma (NHL) aged 2-14 years and 1,312 controls were analyzed. Negative associations were observed between HL and day care attendance [OR = 0.5 (0.2-1.2)] and between HL and repeated early common infections among non-breastfed children [OR = 0.3 (.2-0.7), p = 0.003] [OR for breastfed children: 1.0 (.5-2.1)], but not for the other factors investigated. Negative associations were observed between NHL and birth order 3 or more [OR = 0.7 (0.4-1.1)], prolonged breastfeeding [OR = 0.5 (0.3-1.0)], regular contact with farm animals [OR = 0.5 (0.3-1.0)], frequent farm visits in early life [OR = 0.6 (0.4-1.1)] and history of asthma [OR = 0.6 (0.3-1.1)]. In conclusion, the results partly support the hypothesis that an abnormal maturation of the immune system may play a role in childhood HL or NHL, and call for further investigations.     

Family history of cancer in children with acute leukemia, Hodgkin's lymphoma or non-Hodgkin's lymphoma: the ESCALE study (SFCE)

The role of a family history of cancer in the etiology of childhood hematopoietic malignancies was investigated using the data from the ESCALE study. ESCALE, a population-based case-control study, was carried out in France over the period, 2003-2004. A total of 773 cases of acute leukemia (AL), 130 of Hodgkin's lymphoma (HL), 163 of non-Hodgkin's lymphoma (NHL) and 1,681 population-based controls were included. The controls were randomly selected from the French population and were frequency matched with the cases on age and gender. Cancer history in first- and second-degree relatives was reported by the mothers in a structured telephone questionnaire that was the same for the cases and controls. Odds ratios (ORs) were estimated using an unconditional regression model taking into account the stratification variables and potential confounders. A family history of cancer was associated with an increased risk of HL (OR = 1.5 [1.0-2.2]) and NHL (OR = 1.8 [1.3-2.5]), but not AL (OR = 1.0 [0.9-1.2]). The ORs were higher when at least 2 relatives had a history of cancer or when 1 case occurred before age 46 years. Only HL was significantly associated with a family history of hematopoietic malignancies (OR = 2.0 [1.0-3.8]), mainly because of a significant association with a history of HL (OR = 5.4 [1.3-22]). In conclusion, the study findings support the hypothesis of familial susceptibility to childhood lymphoma, but do not suggest familial susceptibility to childhood AL.     

Characteristics and survival of patients with non-Hodgkin's lymphoma with and without acquired immunodeficiency syndrome

Our objective was to determine the characteristics and survival of patients with non-Hodgkin's lymphoma (NHL) with and without acquired immunodeficiency syndrome (AIDS). A cancer registry and AIDS registry linkage for San Diego County was performed in October 1998 as part of a national multicentre study. We performed Kaplan-Meier analysis to compare survival in NHL patients with and without AIDS, after matching for age, sex, and race/ethnicity. We performed logistic regression to determine which patient and tumour characteristics were significantly associated with 1-year survival. Of the 4361 cases of NHL, 324 (7%) had AIDS and 4037 (93%) were not known to have AIDS. Patients with AIDS were more likely to have extranodal, high-grade, and disseminated NHL diagnosed by non-histologic means and were less likely to have received chemotherapy. Patients with AIDS and NHL who survived at least 1 year had less advanced disease stage and received chemotherapy. The median survival in patients with AIDS was 4 months (95% confidence interval (CI): 4-5) and 95 months (95% CI: 58-157) in patients without AIDS (P<0.001). Although these patients with AIDS-related NHL were unlikely to survive, the highly active antiretroviral agents currently used may improve outcomes in future patients.     

Consolidative involved field radiotherapy after high dose chemotherapy and autologous stem cell transplantation for non-Hodgkin's lymphoma: a case-control study

The role of involved field radiation therapy (IF-RT) after high dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) for non-Hodgkin's lymphoma (NHL) has not been conclusively defined. It has been hypothesized that HDC might obviate the need of consolidative IF-RT. A retrospective matched-pair analysis of patients undergoing HDC and ASCT with or without consolidative IF-RT has been performed. Fifteen patients treated with IF-RT after ASCT were compared with 15 patients without IF-RT, identical for histology, stage and treatment response to HDC/ASCT as well as comparable for international prognostic index (IPI) score, age and gender. After a mean follow-up time of 65 +/- 45 months, none of the patients with consolidative IF-RT following HDC and ASCT relapsed within the involved field compared to six patients without consolidative IF-RT (IF-failure risk at 5 years: 0% vs. 40%; p < 0.005). In most of the cases, local relapse was seen in patients with bulky disease. The 5-year risk for loco-regional failure was 7% after consolidative IF-RT and 38% in patients without IF-RT (p = 0.02) while the 5-year risk for developing distant recurrences was similar in both groups (30% with IF-RT vs. 35% non-IF-RT; p = 0.7). Overall survival at 5 years was similar with 79% (IF-RT) and 65% (non-IF-RT), respectively (p = 0.2). Acute toxicity due to consolidative IF-RT was mild in most cases and severe acute toxicity was noticed in only one patient (7%). Long-term toxicities observed after IF-RT were coronary artery disease, secondary malignancy unrelated to the RT-field, angina abdominalis, hypothyroidism and teeth decay. Recurrence of NHL at sites of macroscopic disease remains common despite HDC. IF-RT achieves excellent local regional control and consolidative IF-RT after ASCT seems indicated, particularly in patients with bulky disease. In the absence of a prospective randomized trial and proven impact on survival rates, IF-RT can be recommended as an option post-ASCT to enhance local disease control.     

Tobacco smoking, alcohol drinking and non-Hodgkin's lymphoma: A European multicenter case-control study (Epilymph)

To study the role of tobacco smoking and alcohol drinking in the etiology of non-Hodgkin's lymphoma (NHL), we conducted a multicenter case-control study in Spain, France, Germany, Italy, Ireland and Czech Republic between 1998 and 2004, which included 1,742 cases of NHL and 2,465 controls matched on age, sex and recruitment area. Tobacco smoking was not associated with the risk of NHL overall or with risk of specific histological subtypes. Similarly, there was no association between alcohol drinking and the risk of NHL overall or across histological subtypes. However, a protective effect of alcohol drinking was observed among men (OR = 0.76, 95% CI = 0.62-0.93) and in non-Mediterranean countries (OR = 0.73, 95% CI = 0.61-0.86). There was no evidence of interaction between alcohol drinking and tobacco smoking in NHL etiology. The results of this large-scale European study did not support an association between tobacco and NHL and suggested a protective effect of alcohol on development of NHL for men and in non-Mediterranean countries.     

Increasing incidence of non-Hodgkin's lymphoma in Canada, 1970-1996: age-period-cohort analysis

Previous studies have shown that the incidence of non-Hodgkin's lymphoma (NHL) has increased in many parts of the world in recent decades. Using data obtained from the Canadian Cancer Registry, the present study examined time trends in NHL incidence in Canada between 1970 and 1996 and the effects of age, period of diagnosis and birth cohort on incidence patterns for each sex separately. Results showed that overall age-adjusted incidence rates increased substantially, from 7.3 and 5.2 per 100,000 in 1970-1971 to 14.0 and 10.0 per 100,000 in 1995-1996 in males and females, respectively. Diffuse lymphoma was the major histological subtype, accounting for approximately 76% of NHL cases over the 27-year period. The data suggest that period effects have played a major role, although birth cohort effects may also have been involved. Sex-specific patterns of the incidence were similar over the time period of diagnosis but were distinct among recent birth cohorts. In conclusion, there is in fact a marked increase in NHL in Canada which cannot be explained in terms of improvements in diagnosis, changes in NHL classification and the increase in AIDS-associated NHL alone. The birth cohort effect in NHL suggests that changes in risk factors may have contributed to the observed increase.