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Background

Non-Hodgkin lymphoma (NHL) is a malignancy etiologically linked to immunomodulatory exposures and disorders. Endogenous female sex hormones may modify immune function and influence NHL risk. Few studies have examined associations between reproductive factors, which can serve as surrogates for such hormonal exposures, and NHL risk by subtype.

Methodology/Principal Findings

Women in the California Teachers Study cohort provided detailed data in 1995–1996 on reproductive history. Follow-up through 2007 identified 574 women with incident B-cell NHL. Hazard rate ratios (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models to assess associations between reproductive factors and all B-cell NHL combined, diffuse large B-cell lymphomas, follicular lymphomas, and B-cell chronic lymphocytic leukemias/small lymphocytic lymphomas. Pregnancy was marginally associated with lower risk of B-cell NHL (RR = 0.84, 95% CI = 0.68–1.04). Much of the reduction in risk was observed after one full-term pregnancy relative to nulligravid women (RR = 0.75, 95% CI = 0.54–1.06; P for trend <0.01), particularly for diffuse large B-cell lymphomas (P for trend = 0.13), but not among women who had only incomplete pregnancies. Age at first full-term pregnancy was marginally inversely associated with B-cell NHL risk overall (P for trend = 0.08) and for diffuse large B-cell lymphomas (P for trend = 0.056). Breast feeding was not associated with B-cell NHL risk overall or by subtype.

Conclusions

Full-term pregnancy and early age at first full-term pregnancy account for most of the observed reduction in B-cell NHL risk associated with gravidity. Pregnancy-related hormonal exposures, including prolonged and high-level exposure to progesterone during a full-term pregnancy may inhibit development of B-cell NHL.

Several previous studies found inverse associations between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) and multiple myeloma. However, most studies were retrospective, and few distinguished former drinkers or infrequent drinkers from consistent nondrinkers. Therefore, the authors investigated whether history of alcohol drinking affected risks of NHL and multiple myeloma among 102,721 eligible women in the California Teachers Study, a prospective cohort study in which 496 women were diagnosed with B-cell NHL and 101 were diagnosed with multiple myeloma between 1995–1996 and December 31, 2007. Incidence rate ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Risk of all types of B-cell NHL combined or multiple myeloma was not associated with self-reported past consumption of alcohol, beer, wine, or liquor at ages 18–22 years, at ages 30–35 years, or during the year before baseline. NHL subtypes were inconsistently associated with alcohol intake. However, women who were former alcohol drinkers at baseline were at elevated risk of overall B-cell NHL (rate ratio = 1.46, 95% confidence interval: 1.08, 1.97) and follicular lymphoma (rate ratio = 1.81, 95% confidence interval: 1.00, 3.28). The higher risk among former drinkers emphasizes the importance of classifying both current and past alcohol consumption and suggests that factors related to quitting drinking, rather than alcohol itself, may increase B-cell NHL risk.

Dietary phytochemical compounds, including isoflavones and isothiocyanates, may inhibit cancer development but have not yet been examined in prospective epidemiologic studies of ovarian cancer. The authors have investigated the association between consumption of these and other nutrients and ovarian cancer risk in a prospective cohort study. Among 97,275 eligible women in the California Teachers Study cohort who completed the baseline dietary assessment in 1995–1996, 280 women developed invasive or borderline ovarian cancer by December 31, 2003. Multivariable Cox proportional hazards regression, with age as the timescale, was used to estimate relative risks and 95% confidence intervals; all statistical tests were two sided. Intake of isoflavones was associated with lower risk of ovarian cancer. Compared with the risk for women who consumed less than 1 mg of total isoflavones per day, the relative risk of ovarian cancer associated with consumption of more than 3 mg/day was 0.56 (95% confidence interval: 0.33, 0.96). Intake of isothiocyanates or foods high in isothiocyanates was not associated with ovarian cancer risk, nor was intake of macronutrients, antioxidant vitamins, or other micronutrients. Although dietary consumption of isoflavones may be associated with decreased ovarian cancer risk, most dietary factors are unlikely to play a major role in ovarian cancer development.

Nutritional status and physical activity are known to alter immune function, which may be relevant to lymphomagenesis. The authors examined body size measurements and recreational physical activity in relation to risk of B-cell non-Hodgkin lymphoma (NHL) in the prospective California Teachers Study. Between 1995 and 2007, 574 women were diagnosed with incident B-cell NHL among 121,216 eligible women aged 22–84 years at cohort entry. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models for all B-cell NHL combined and for the 3 most common subtypes: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Height was positively associated with risk of all B-cell NHLs (for >1.70 vs. 1.61–1.65 m, relative risk = 1.50, 95% confidence interval: 1.16, 1.96) and chronic lymphocytic leukemia/small lymphocytic lymphoma (relative risk = 1.93, 95% confidence interval: 1.09, 3.41). Weight and body mass index at age 18 years were positive predictors of B-cell NHL risk overall. These findings indicate that greater height, which may reflect genetics, early life immune function, infectious exposures, nutrition, or growth hormone levels, may play a role in NHL etiology. Adiposity at age 18 years may be more relevant to NHL etiology than that in later life.

We examined oral contraceptive (OC) and menopausal hormonal therapy (MHT) use in relation to risk of B-cell non-Hodgkin lymphoma (NHL). Women under age 85 years participating in the California Teachers Study with no history of hematopoietic cancer were followed from 1995 through 2007. 516 of 114,131 women eligible for OC use analysis and 402 of 54,758 postmenopausal women eligible for MHT use analysis developed B-cell NHL. Multivariable adjusted and stratified Cox proportional hazards models were fit to estimate relative risks (RR) and 95% confidence intervals (95% CI). Ever versus never OC use was marginally associated with lower B-cell NHL risk, particularly among women first using OCs before age 25 years (RR=0.72, 95%CI=0.51-0.99); yet, no duration-response effect was observed. No association was observed for ever versus never MHT use among postmenopausal women (RR=1.05, 95%CI=0.83-1.33) overall, or by formulation (estrogen alone, ET, or estrogen plus progestin, EPT). Among women with no MHT use, having bilateral oophorectomy plus hysterectomy was associated with greater B-cell NHL risk than having natural menopause (RR=3.15, 95%CI=1.62-6.13). Bilateral oophorectomy plus hysterectomy was not associated with risk among women who used ET or EPT. These results indicate that exogenous hormone use does not strongly influence B-cell NHL risk.

Objective

To investigate risk factors for non‐Hodgkin's lymphoma (NHL) and analyse NHL subtypes and characteristics in patients with systemic lupus erythematosus (SLE).

Methods

A national SLE cohort identified through SLE discharge diagnoses in the Swedish hospital discharge register during 1964 to 1995 (n = 6438) was linked to the national cancer register. A nested case control study on SLE patients who developed NHL during this observation period was performed with SLE patients without malignancy as controls. Medical records from cases and controls were reviewed. Tissue specimens on which the lymphoma diagnosis was based were retrieved and reclassified according to the WHO classification. NHLs of the subtype diffuse large B cell lymphoma (DLBCL) were subject to additional immunohistochemical staining using antibodies against bcl‐6, CD10 and IRF‐4 for further subclassification into germinal centre (GC) or non‐GC subtypes.

Results

16 patients with SLE had NHL, and the DLBCL subtype dominated (10 cases). The 5‐year overall survival and mean age at NHL diagnosis were comparable with NHL in the general population—50% and 61 years, respectively. Cyclophosphamide or azathioprine use did not elevate lymphoma risk, but the risk was elevated if haematological or sicca symptoms, or pulmonary involvement was present in the SLE disease. Two patients had DLBCL‐GC subtype and an excellent prognosis.

Conclusions

NHL in this national SLE cohort was predominated by the aggressive DLBCL subtype. The prognosis of NHL was comparable with that of the general lymphoma population. There were no indications of treatment‐induced lymphomas. Molecular subtyping could be a helpful tool to predict prognosis also in SLE patients with DLBCL.

Family history of haematopoietic malignancies appears to be a risk factor for non-Hodgkin's lymphoma (NHL), but whether risk varies by family member's gender is unclear. Among 121 216 women participating in the prospective California Teachers Study, NHL risk varied by type of haematopoietic malignancy and gender of the relative.

INTRODUCTION

Vital statistics for the lymphoid malignancies obtained from the Surveillance, Epidemiology and End Results (SEER) Program have seldom been directly compared to data from alternative national databases; while SEER is recognized as the standard, some lymphoid malignancies—especially the chronic ones—may be underreported.

METHODS

We compared the incidence, all-cause, and cause-specific mortality for Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) in SEER to that in the Nurses' Health Study (NHS), a national cohort study of 121,700 female registered nurses, matching for age and race.

RESULTS

In over 2.5 million person-years, the incidence of HL was the same as in SEER (SIR= 1.01 [0.75, 1.26]), while the incidence of NHL, CLL and MM were slightly higher. All-cause mortality was lower for the lymphoid malignancies except for MM, which was the same; there were no differences in cause-specific mortality, except for MM (HR= 1.26 [1.07, 1.48]).

CONCLUSION

Our analysis suggests that, at least among white women, SEER is a reliable data source with respect to lymphoid malignancies.

Although advanced parental age at one's birth has been associated with increased risk of breast and prostate cancers, few studies have examined its effect on adult-onset sporadic hematologic malignancies. The authors examined the association of parents’ ages at women's births with risk of hematologic malignancies among 110,999 eligible women aged 22–84 years recruited into the prospective California Teachers Study. Between 1995 and 2007, 819 women without a family history of hematologic malignancies were diagnosed with incident lymphoma, leukemia (primarily acute myeloid leukemia), or multiple myeloma. Multivariable-adjusted Cox proportional hazards models provided estimates of relative risks and 95% confidence intervals. Paternal age was positively associated with non-Hodgkin lymphoma after adjustment for race and birth order (relative risk for age ≥40 vs. <25 years = 1.51, 95% confidence interval: 1.08, 2.13; P-trend = 0.01). Further adjustment for maternal age did not materially alter the association. By contrast, the elevated non-Hodgkin lymphoma risk associated with advanced maternal age (≥40 years) became null when paternal age was included in the statistical model. No association was observed for acute myeloid leukemia or multiple myeloma. Advanced paternal age may play a role in non-Hodgkin lymphoma etiology. Potential etiologic mechanisms include de novo gene mutations, aberrant paternal gene imprinting, or telomere/telomerase biology.

This study explored the association between dietary vitamin D and non-Hodgkin lymphoma (NHL) risk. The Multiethnic Cohort (MEC) includes more than 215,000 Caucasians, African Americans, Native Hawaiians, Japanese Americans, and Latinos, aged 45-75. After 10 years of follow-up, 939 incident NHL cases were identified. Risk was estimated using Cox proportional hazards models adjusted for possible confounders. Vitamin D intake was not associated with NHL risk in the entire cohort (Ptrend=0.72 for men and Ptrend=0.83 for women), but significantly lowered disease risk in African American women (HR=0.50, 95% CI: 0.28-0.90, Ptrend=0.03) and was borderline protective in African American men (HR=0.68; 95% CI: 0.39-1.19; Ptrend=0.31) when the highest to the lowest tertile was compared. In NHL subtype analyses, a 19%, 36%, and 32% lowered risk, although not significant, was observed for diffuse large B-cell lymphoma, follicular lymphoma, and small lymphocytic lymphoma/chronic lymphocytic leukemia in women, respectively. High dietary intake of vitamin D did not show a protective effect against NHL within the MEC except among African Americans, possibly because vitamin D production due to sun exposure is limited in this population.

Reasons for higher incidence of lymphoid neoplasms among men than women are unknown. Because female sex hormones have immunomodulatory effects, reproductive factors and exogenous hormone use may affect risk for lymphoid malignancies. Previous epidemiologic studies on this topic have yielded conflicting results. Within the National Institutes of Health-AARP Diet and Health Study cohort, we prospectively analyzed detailed, questionnaire-derived information on menstrual and reproductive factors and use of oral contraceptives and menopausal hormone therapy among 134,074 US women. Using multivariable proportional hazards regression models, we estimated relative risks (RRs) for 85 plasma cell neoplasms and 417 non-Hodgkin lymphomas (NHLs) identified during follow-up from 1996-2002. We observed no statistically significant associations between plasma cell neoplasms, NHL, or the three most common NHL subtypes and age at menarche, parity, age at first birth, oral contraceptive use, or menopausal status at baseline. For menopausal hormone therapy use, overall associations between NHL and unopposed estrogen and estrogen plus progestin were null, with the potential exception of an inverse association (RR=0.49, 95% CI, 0.25-0.96) between use of unopposed estrogen and diffuse large B-cell lymphoma (DLBCL), the most common NHL subtype, among women with a hysterectomy. These data do not support an important role for reproductive factors or exogenous hormones in modulating lymphomagenesis.

Background

The etiology of malignant lymphoma is still largely unknown. This study determines the relationship between exposure to pesticides and the occurrence of lymphoid neoplasms in Shiraz, Southern Iran.

Methods

Between 2007 and 2008, in a case control study conducted in Nemazee Hospital in Shiraz, Southern Iran, 200 subjects diagnosed with lymphoma according to the World Health Organization (WHO) classification were enrolled. Controls (n=200) were frequency matched to the cases by sex, age, and center. Subjects who were a farmer were compared with all other occupations.

Results

Out of the 200 cases that were diagnosed as lymphoid neoplasms, 100 were non-Hodgkin's lymphoma, 54 Hodgkin's lymphoma and 46 multiple myeloma. Seventy two percent of the NHL's were of the B-cell type, 15% of the T-cell type and the rest were not classified. Furthermore, subjects exposed to pesticides were at an increased risk of non-Hodgkin lymphoma and MM, but not Hodgkin lymphoma.

Conclusion

Risk of non-Hodgkin lymphoma and MM was highest for exposure to pesticides, among them, insecticide's risk was confirmed.

Background

Malignancies of the lymphoid cells, including non-Hodgkin lymphomas (NHLs), Hodgkin lymphoma (HL) and multiple myeloma (MM), occur at much lower rates in Asians than other racial/ethnic groups in the United States (US). It remains unclear whether these deficits are explained by genetic or environmental factors. To better understand environmental contributions, we examined incidence patterns of lymphoid malignancies among populations characterized by ethnicity, birthplace, and residential neighborhood socioeconomic status (SES) and ethnic enclave status.

Methods

We obtained data regarding all Asian patients diagnosed with lymphoid malignancies between 1988 and 2004 from the California Cancer Registry and neighborhood characteristics from US Census data.

Results

While incidence rates of most lymphoid malignancies were lower among Asian than white populations, only follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and nodular sclerosis (NS) HL rates were statistically significantly lower among foreign-born than US-born Asians, with incidence rate ratios ranging from 0.34 to 0.87. Rates of CLL/SLL and NS HL were also lower among Asian women living in ethnic enclaves or lower-SES neighborhoods than those living elsewhere. Conclusions: These observations support strong roles of environmental factors in the causation of FL, CLL/SLL, and NS HL.

Impact

Studying specific lymphoid malignancies in US Asians may provide valuable insight towards understanding their environmental causes.

Few studies of reproductive hormone exposures and non-Hodgkin lymphoma (NHL) have examined NHL subtypes. Associations between reproductive hormonal factors and risk of all NHL and of two predominant subtypes, diffuse large-cell lymphoma (DLCL) (n = 233) and follicular lymphoma (n = 173), were investigated among women (n = 581) in a large, population-based, case-control study (1,591 cases, 2,515 controls). Controls (n = 836) identified by random digit dialing were frequency matched by age and county to incident NHL cases ascertained in the San Francisco Bay Area of California in 1988–1993. Adjusted unconditional logistic regression was used to obtain odds ratios. More than four pregnancies indicated a possible lower risk of all NHL (odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.55, 1.2; p-trend = 0.06) and of DLCL (OR = 0.53, 95% CI: 0.31, 0.90; p-trend = 0.01). Exclusive use of menopausal hormone therapy for ≥5 years was associated with a reduced risk of all NHL (OR = 0.68, 95% CI: 0.48, 0.98) and of DLCL (OR = 0.50, 95% CI: 0.30, 0.85). Oral contraceptive use indicated a lower risk of all NHL (OR = 0.68, 95% CI: 0.49, 0.94), and perhaps DLCL (OR = 0.79, 95% CI: 0.51, 1.2), and of follicular lymphoma (OR = 0.75, 95% CI: 0.46, 1.2). Results suggest that endogenous and exogenous reproductive hormones confer different risks by NHL subtype and are associated with a reduced risk of DLCL in women.

Allogeneic hematopoietic cell transplantation (HCT) can be curative for both myelodysplastic syndromes (MDS) and lymphoid malignancies. Little is known about the efficacy of allogeneic HCT in patients in whom both myeloid and lymphoid disorders are present at the time of HCT. We analyzed outcomes in 21 patients with MDS and concurrent lymphoid malignancy when undergoing allogeneic HCT. Seventeen patients had received extensive prior cytotoxic chemotherapy, including autologous HCT in seven, for non-Hodgkin lymphoma (NHL, n=7), Hodgkin lymphoma (HL, n=2), chronic lymphocytic leukemia (CLL, n=5), NHL plus HL (n=1), multiple myeloma (n=1), or T-cell acute lymphocytic leukemia (ALL) (n=1), and had, presumably, developed MDS as a consequence of therapy. Four previously untreated patients had CLL. Nineteen patients were conditioned with high-dose (n=14) or reduced-intensity regimens (n=5), and transplanted from HLA-matched or one antigen/allele mismatched related (n=10) or unrelated (n=9) donors; two patients received HLA-haploidentical related transplants following conditioning with a modified conditioning regimen. Currently, 2 of 4 previously untreated, and 2 of 17 previously treated patients are surviving in remission of both MDS and lymphoid malignancies. However, the high non-relapse mortality among previously treated patients, even with reduced-intensity conditioning regimens, indicates that new transplant strategies need to be developed.

The Swedish Family-Cancer Database was used to analyse site-specific risk of second primary malignancies following 53 159 haematolymphoproliferative disorders (HLPD) diagnosed between 1958 and 1996. Standardized incidence ratio (SIR) of a second malignancy was calculated as the ratio of observed to expected numbers of second malignancies by applying site-, sex-, age-, period-, residence- and occupation-specific rates in the corresponding population in the Database to the appropriate person-years at risk. Among 18 960 patients with non-Hodgkin's lymphoma (NHL), there was over a 3-fold significant increase in cancer of the tongue, small intestine, nose, kidney and nervous system, squamous cell carcinoma (SCC) of the skin, NHL, Hodgkin's disease (HD) and lymphoid and myeloid leukaemia. Among 5353 patients with HD, there was over a 4-fold significant increase in cancer of the salivary glands, nasopharynx and thyroid, NHL and myeloid leukaemia, and over a 1.6-fold increase in cancer of the stomach, colon, lung, breast, skin (melanoma and SCC), nervous system and soft tissues and lymphoid leukaemia. Among 28 846 patients with myeloma and leukaemia, there was a significant increase in cancer of the skin, nervous system and non-thyroid endocrine glands and all HLPD except for myeloma. Our findings showed some clustering between first and second primaries among Epstein–Barr virus-, ultraviolet radiation- and immunosuppression-related cancers. © 2001 Cancer Research Campaignhttp://www.bjcancer.com

Objectives

Investigating the relationship between occupational exposure to pesticides and the risk of lymphoid neoplasms (LN) in men.

Methods

A hospital-based case-control study was conducted in six centres in France between 2000 and 2004. The cases were incident cases with a diagnosis of lymphoid neoplasm aged 18 to 75 years. During the same period, controls of the same age and gender as the cases were recruited in the same hospital, mainly in the orthopaedic and rheumatological departments. Exposures to pesticides were evaluated through specific interviews and case-by-case expert reviews. Four hundred and ninety-one cases (244 cases of non-Hodgkin’s lymphoma (NHL), 87 of Hodgkin’s lymphoma (HL), 104 of lymphoproliferative syndromes (LPS) and 56 of multiple myeloma (MM) cases) and 456 controls were included in the analyses. The odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regressions.

Results

Positive associations between HL and occupational exposure to triazole fungicides and urea herbicides were observed (OR=8.4 [2.2–32.4], 10.8 [2.4–48.1] respectively). Exposure to insecticides, fungicides and herbicides were linked to a three-fold increases in MM risk (OR=2.8 [1.2–6.5], 3.2 [1.4–7.2], 2.9 [1.3–6.5]). For LPS subtypes, associations restricted to hairy-cell leukaemia (HCL) were evidenced for exposure to organochlorine insecticides, phenoxy herbicides and triazine herbicides (OR=4.9 [1.1–21.2], 4.1 [1.1–15.5], 5.1 [1.4–19.3]), although based on small numbers. Lastly, despite the increased odds ratios for organochlorine and organophosphate insecticides, carbamate fungicides and triazine herbicides, no significant associations were evidenced for NHL.

Conclusions

The results, based on case-by-case expert review of occupation-specific questionnaires, support the hypothesis that occupational pesticide exposures may be involved in HL, MM and HCL and do not rule out a role in NHL. The analyses identified specific pesticides that deserve further investigation and the findings were consistent with those of previous studies.

Objective

The development of non-Hodgkin's lymphoma (NHL) confers a high risk of mortality in primary Sjögren's syndrome (pSS) patients, but the sensitivity and specificity of proposed lymphoma predictors are insufficient for practical use. The performance of lymphoid organisation in the form of germinal centre (GC)-like lesions was evaluated in labial salivary gland biopsies taken at pSS diagnosis as a potential lymphoma-predicting biomarker.

Methods

Labial salivary gland tissue biopsies available from two Swedish pSS research cohorts (n=175) were re-evaluated by light microscopy in a blind study in order to identify GC-like structures as a sign of ectopic lymphoid tissue formation and organisation. A linkage study was performed with the Swedish Cancer Registry for lymphoma identification. The risk of developing NHL in GC-positive patients in comparison with GC-negative patients was evaluated using Kaplan–Meier statistics and log-rank test. Associations between GC-like structures and clinical and/or laboratory disease markers were also determined using χ2 or Fisher's exact tests.

Results

At diagnosis, 25% of pSS patients had GC-like structures in their salivary glands. Seven of the 175 patients studied (14% GC+ and 0.8% GC−) developed NHL during 1855 patient-years at risk, with a median onset of 7 years following the initial diagnostic salivary gland biopsy. Six of the seven patients had GC-like structures at diagnosis; the remaining patient was GC negative at the time of diagnosis (p=0.001).

Conclusions

The detection of GC-like structures by light microscopy in pSS diagnostic salivary biopsies is proposed as a highly predictive and easy-to-obtain marker for NHL development. This allows for risk stratification of patients and the possibility to initiate preventive B-cell-directed therapy.

Severe immune dysfunction is an established risk factor of lymphoma, but the role of moderate alterations of immunity is not clear and prospective investigations are needed. We examined several immune-related disorders and medications in relation to non-Hodgkin lymphoma (NHL) in the Multiethnic Cohort. Over 215,000 subjects of African American, Caucasian, Japanese American, Latino, and Native Hawaiian ancestry aged 45–75 years completed a questionnaire, including information on medical history, in 1993–1996. After exclusions, we performed Cox regression among 193,050 cohort members including 939 incident NHL cases while adjusting for sex, age, ethnicity, education, body mass index, and alcohol intake. Self-reported diabetes was not associated with NHL overall, but was positively associated with risk among Japanese Americans (hazard ratio (HR) = 1.55; 95% confidence interval (CI): 1.10–2.17). Participants with a history of blood transfusion were at increased risk with HR = 1.39 (95% CI: 1.06–1.84) in men and HR = 1.22 (95% CI: 0.94–1.58) in women, especially for the diffuse large B-cell lymphoma subtype. History of asthma or other allergies was associated with elevated risk only among Latinos (HR = 1.46; 95% CI: 1.07–2.00) who also showed a significant relation between current use of antihistamines and NHL (HR = 1.80; 95% CI: 1.09–2.97). Use of non-steroidal anti-inflammatory drugs was not associated with NHL. Our findings from this large prospective study support a moderate risk for NHL related to blood transfusions, current long-term antihistamine use, and diabetes, but the associations were limited to a certain ethnic groups and require further replications.

The incidence of non-Hodgkin lymphoma has substantially increased during the past several decades, and although established risk factors such as immunodeficiency and viral infection may be responsible for a portion of the cases, the vast majority of the NHL cases remain unexplained. Dietary nitrate and nitrite intake are exposures of particular interest for non-Hodgkin lymphoma risk as they have been shown to cause lymphomas in animal studies and there is growing evidence of adverse impact in the epidemiological literature. We investigated NHL risk in general and by subtype in relation to dietary nitrate and nitrite intake in a population-based case-control study of 1,304 women in Connecticut. Nitrate and nitrite intake was assessed using a 120-item food frequency questionnaire. We found no association between risk of NHL and dietary nitrate and a slightly increased risk of NHL for higher dietary nitrite intake (OR = 1.37; 95% CI: 1.04–1.79). The risk was significantly increased for diffuse large B-cell lymphoma (OR = 1.61; 95% CI: 1.08–2.42), follicular lymphoma (OR = 1.61; 95% CI: 1.02–2.54), and T-cell lymphoma (OR = 2.38; 95% CI: 1.12–5.06). Animal products containing nitrite appear to be driving the risk for DLBC lymphoma and follicular lymphoma, whereas the risk for T-cell lymphoma is being driven by plant products. Our results confirm a previous finding for nitrite intake and highlight the importance of evaluating NHL risk by histologic type. We conclude that these results should be replicated in a larger study with data on water consumption as well as diet.

Epidemiologic studies conducted to date have shown evidence of a causal relation between smoking and non-Hodgkin lymphoma (NHL) risk. However, previous studies did not account for passive smoking exposure in the never-smoking reference group. The California Teachers Study collected information about lifetime smoking and household passive smoking exposure in 1995 and about lifetime exposure to passive smoking in 3 settings (household, workplace, and social settings) in 1997–1998. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models with follow-up through 2007. Compared with never smokers, ever smokers had a 1.11-fold (95% confidence interval (CI): 0.94, 1.30) higher NHL risk that increased to a 1.22-fold (95% CI: 0.95, 1.57) higher risk when women with household passive smoking were excluded from the reference category. Statistically significant dose responses were observed for lifetime cumulative smoking exposure (intensity and pack-years; both P ’s for trend = 0.02) when women with household passive smoking were excluded from the reference category. Among never smokers, NHL risk increased with increasing lifetime exposure to passive smoking (relative risk = 1.51 (95% CI: 1.03, 2.22) for >40 years vs. ≤5 years of passive smoking; P for trend = 0.03), particularly for follicular lymphoma (relative risk = 2.89 (95% CI: 1.23, 6.80); P for trend = 0.01). The present study provides evidence that smoking and passive smoking may influence NHL etiology, particularly for follicular lymphoma.

Non-Hodgkin lymphoma (NHL) represents a group of heterogeneous diseases that significantly vary in their causes, molecular profiles, and natural progression. In 2006, there will be ~59,000 newly diagnosed NHL cases in the U.S. and over 300,000 cases worldwide. While new therapeutic regimens are minimizing the number of deaths related to NHL, causes for the majority of lymphomas remain undetermined. Recent studies suggest that dietary factors may contribute to the rising rates of NHL. This review will summarize epidemiological reports that have studied the relationship between obesity, physical activity, diet and risk of NHL.

Based on a number of case-control and prospective cohort studies, overweight/obesity likely increases the risk of NHL; whereas, moderate physical activity may reduce risk. Several studies support an inverse association between intakes of vegetables and NHL risk, particularly for the consumption of cruciferous vegetables. This may relate to the induction of apoptosis and growth arrest in pre-neoplastic and neoplastic cells, two important actions of isothiocyanates found in cruciferous vegetables. Studies also suggest that fish intake may be inversely associated with risk of NHL, though findings have not been entirely consistent. This may relate to the high organochlorine content in some fish that could override a protective effect. High consumption of fats, meat and dairy products also may increase lymphoma risk. The accumulated scientific evidence concerning the associations between obesity, diet, and NHL suggests several identified modifiable risk factors that might be recommended to decrease lymphoma risk.

Summary

This study described long-term outcomes of autologous hematopoietic-cell transplantation (HCT) for advanced Hodgkin (HL) and non-Hodgkin lymphoma (NHL). The study included recipients of autologous HCT for HL (N=407) and NHL (N=960) from 1990–98 who were in continuous complete remission for at least 2 years post-HCT. Median follow-up was 104 months for HL and 107 months for NHL. Overall survival at 10-years was 77% (72–82%) for HL, 78% (73–82%) for diffuse large-cell NHL, 77% (71–83%) for follicular NHL, 85% (75–93%) for lymphoblastic/Burkitt NHL, 52% (37–67%) for mantle-cell NHL and 77% (67–85%) for other NHL. On multivariate analysis, mantle-cell NHL had the highest relative-risk for late mortality (2.87 (1.70–4.87)), while the risks of death for other histologies were comparable. Relapse was the most common cause of death. Relative mortality compared to age, race and gender adjusted normal population remained significantly elevated and was 14.8 (6.3–23.3) for HL and 5.9 (3.6–8.2) for NHL at 10-years post-HCT. Recipients of autologous HCT for HL and NHL who remain in remission for at least 2-years have favorable subsequent long-term survival but remain at risk for late relapse. Compared to the general population, mortality rates continue to remain elevated at 10-years post-transplantation.

Previous studies have examined the association between individual foods or nutrients, but not overall diet, and ovarian cancer risk. To account for the clustering of foods in the diet, we investigated the association between dietary patterns and risk of ovarian cancer in the prospective California Teachers Study cohort. Of 97,292 eligible women who completed the baseline dietary assessment in 1995–1996, 311 women developed epithelial ovarian cancer on or before December 31, 2004. Based on principal components analysis, five major dietary patterns were identified and termed “plant-based,” “high-protein/high-fat,” “high-carbohydrate,” “ethnic,” and “salad-and-wine.” Multivariable Cox proportional hazards regression analysis was used to estimate associations between these dietary patterns and risk of incident ovarian cancer. Most of the dietary patterns were not significantly associated with ovarian cancer risk. However, women who followed a plant-based diet had higher risk; comparing those in the top quintile of plant-based food intake with those in the lowest quintile, the relative risk of ovarian cancer was 1.65 (95% confidence interval: 1.07–2.54; Ptrend=0.03). Associations with the five dietary patterns did not vary by known ovarian cancer risk factors or other behavioral or sociodemographic characteristics. Overall, our results show no convincing associations between dietary patterns and ovarian cancer risk.

OBJECTIVE—To examine the epidemiologic association between diabetes and risk of non-Hodgkin's lymphoma (NHL).

RESEARCH DESIGN AND METHODS—We searched MEDLINE for observational studies on the association between diabetes and NHL in adults using the keywords “diabetes” and “lymphoma.” Prospective cohort studies that reported relative risks or standardized incidence ratios and case-control studies that reported odds ratios with 95% CIs were included. A random-effects model was used to combine results from the individual studies.

RESULTS—A total of 15 manuscripts (reporting data from 5 prospective cohort and 11 case-control studies) met the inclusion criteria. Combining data from all studies, the risk ratio (RR) of developing NHL in patients with diabetes was 1.19 (95% CI 1.04–1.35). Based on prospective studies, patients with diabetes had an RR of developing NHL of 1.41 (1.07–1.88), without heterogeneity among studies (I2 = 34.3%; P > 0.10). Based on case-control studies, patients with diabetes had an RR of 1.12 (95% CI 0.95–1.31) of developing NHL compared with people without diabetes, with some heterogeneity among studies (I2 = 36.28%; P = 0.09).

CONCLUSIONS—Diabetes is associated with a moderately increased risk of NHL, which is consistent with other reported associations between diabetes and malignancies. Future studies should focus on elucidating potential pathophysiologic links between diabetes and NHL.