We examined whether dietary intake of isoflavones, lignans, isothiocyanates, antioxidants, or specific foods rich in these compounds is associated with reduced risk of B-cell non-Hodgkin lymphoma (NHL), multiple myeloma (MM), or Hodgkin lymphoma (HL) in a large, prospective cohort of women.
Between 1995-1996 and December 31, 2007, among 110,215 eligible members of the California Teachers Study cohort, 536 women developed incident B-cell NHL, 104 developed MM, and 34 developed HL. Cox proportional hazards regression, with age as the time-scale, was used to estimate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for risk of lymphoid malignancies.
Weak inverse associations with risk of diffuse large B-cell lymphoma were observed for isothiocyanates (RR for ≥12.1 vs. <2.7 mcM/day=0.67, 95% CI: 0.43-1.05) and an antioxidant index measuring hydroxyl radical absorbance capacity (RR for ≥2.2 vs. <0.9 μM Trolox equiv/g/day=0.68, 95% CI: 0.42-1.10; ptrend=0.08). Risk of other NHL subtypes, overall B-cell NHL, MM, or HL was not generally associated with dietary intake of isoflavones, lignans, isothiocyanates, antioxidants, or major food sources of these compounds.
Isoflavones, lignans, isothiocyanates, and antioxidant compounds are not associated with risk of most B-cell malignancies, but some phytocompounds may decrease risk of selected subtypes.
lymphoma; diet; isothiocyanates; antioxidants; cohort studies
Epidemiological studies have shown that moderate alcohol drinkers have a lower death rate for all causes. Alcohol drinking has also been associated with reduced risk of non-Hodgkin lymphoma (NHL). Here, we examined the role of alcohol consumption on NHL survival by type of alcohol consumed and NHL subtype.
A cohort of 575 female NHL incident cases diagnosed during 1996–2000 in Connecticut was followed-up for a median of 7.75 years. Demographic, clinical, and lifestyle information was collected at diagnosis. Survival analyses were conducted with Kaplan-Meier methods, and hazard ratios (HR) were estimated from Cox Proportional Hazards models.
Compared to never drinkers, wine drinkers experienced better overall survival (75% vs. 69% five-year survival rates, p-value for log-rank test=0.030) and better disease free survival (70% vs. 67% five-year disease-free survival rates, p-value for log-rank test=0.049). Analysis by NHL subtype shows that the favorable effect of wine consumption was mainly seen for patients diagnosed with diffuse large B-cell lymphoma (DLBCL) (wine drinkers for more than 25 years vs. never drinkers: HR=0.36, 95% CI 0.14–0.94 for overall survival; HR=0.38, 95% CI 0.16–0.94 for disease-free survival), and the adverse effect of liquor consumption was also observed among DLBCL patients (liquor drinkers vs. never drinkers: HR=2.49, 95% CI 1.26–4.93 for disease-free survival).
Our results suggest a moderate relationship between pre-diagnostic alcohol consumption and NHL survival, particularly for DLBCL. The results need to be replicated in larger studies.
Implications for cancer survivors
Pre-diagnostic behaviors might impact the prognosis and survival of NHL patients.
Alcohol; Wine; Liquor; Non-Hodgkin lymphoma; Prognosis; Survival
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.
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.
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.
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.
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.
body mass index; body size; cohort studies; exercise; hip; lymphoma, non-Hodgkin; waist-hip ratio
Whether alcohol consumption influences ovarian cancer risk is unclear. Therefore, we investigated the association between alcohol intake at various ages and risk of ovarian cancer.
Among 90,371 eligible members of the California Teachers Study cohort who completed a baseline alcohol assessment in 1995–1996, 253 women were diagnosed with epithelial ovarian cancer by the end of 2003. Multivariate Cox proportional hazards regression analysis was performed to estimate relative risks (RRs) and 95% confidence intervals (CIs).
Consumption of total alcohol, beer, or liquor in the year prior to baseline, at ages 30–35 years, or at ages 18–22 years was not associated with risk of ovarian cancer. Consumption of at least one glass per day of wine, compared to no wine, in the year before baseline was associated with increased risk of developing ovarian cancer: RR = 1.57 (95% CI 1.11–2.22), Ptrend = 0.01. The association with wine intake at baseline was particularly strong among peri-/post-menopausal women who used estrogen-only hormone therapy and women of high socioeconomic status.
Alcohol intake does not appear to affect ovarian cancer risk. Constituents of wine other than alcohol or, more likely, unmeasured determinants of wine drinking were associated with increased risk of ovarian cancer.
Ovarian cancer; Alcoholic beverages; Cohort studies; Women’s health
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.
non-Hodgkin lymphoma; oral contraceptives; menopausal hormonal therapy; hysterectomy; bilateral oophorectomy
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.
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.
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]).
Our analysis suggests that, at least among white women, SEER is a reliable data source with respect to lymphoid malignancies.
hematologic malignancy; health services research; lymphoma; leukemia; myeloma
The aim of this study was to investigate whether genetic polymorphisms in cytochrome P450s (CYPs), glutathione S-transferases (GSTs) and N-acetyltransferases (NATs) genes modify the relationship between alcohol consumption and risk of non-Hodgkin's Lymphoma (NHL) in a population-based case-control study including 1,115 Connecticut women. Although we did not find strong evidence that the genetic polymorphisms modify the relationship between alcohol consumption and risk of NHL, we identified significant interactions for multiple GSTs and NATs and alcohol intake among persons with DLBCL. Our results confer support investigation of the gene-environment interaction in a larger study population of DLBCL.
Non-Hodgkin lymphoma; alcohol; genetic polymorphisms; GST; CYPs; NATs
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.
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.
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.
Studying specific lymphoid malignancies in US Asians may provide valuable insight towards understanding their environmental causes.
lymphoid malignancies; Asians; immigration; environmental causes
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.
cohort studies; hematologic neoplasms; leukemia, myeloid, acute; lymphoma, non-Hodgkin; maternal age; paternal age
HIV-infected persons treated with highly active antiretroviral therapy (HAART) continue to have elevated risk for non-Hodgkin lymphoma (NHL). We conducted a retrospective cohort study of NHL among patients at an urban HIV clinic (N=3025). Proportional hazards models identified immunologic and virologic predictors of NHL. Sixty-five NHLs arose during 1989-2006. NHL incidence declined over time. Nonetheless, 51 NHLs (78%) occurred within the HAART era (1996-2006). NHL risk increased with declining CD4 count (p-trend<0.0001) and increasing HIV viral load (p-trend=0.005). In a multivariable model, NHL risk was independently associated with both current CD4 count (hazard ratios 7.7 and 3.8, respectively, for CD4 counts 0-99 and 100-249 vs. 250+ cells/mm3; p-trend<0.0001) and prior time spent with a viral load above 5.00 log10 copies/ml (hazard ratios of 3.4, 2.6, and 6.8, respectively, for 0.1-0.4, 0.5-1.4, and 1.5+ years vs. 0 years; p-trend=0.004). Although serum globulin levels were elevated compared to the general population, NHL risk was unrelated to this B-cell activation marker (p=0.39). Among HIV-infected individuals in the HAART era, NHLs are linked to immunosuppression and extended periods of uncontrolled HIV viremia. The association with high-level viremia could reflect detrimental effects on immune function related to incompletely effective HAART or direct effects on B-cells.
non-Hodgkin lymphoma; acquired immunodeficiency syndrome; human immunodeficiency virus; immunosuppression; Epstein Barr virus; inflammation
To investigate risk factors for non‐Hodgkin's lymphoma (NHL) and analyse NHL subtypes and characteristics in patients with systemic lupus erythematosus (SLE).
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.
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.
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.
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.
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.
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.
Risk of non-Hodgkin lymphoma and MM was highest for exposure to pesticides, among them, insecticide's risk was confirmed.
Exposure; Pesticide; Non-Hodgkin lymphoma; Hodgkin lymphoma; Multiple myeloma
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.
To investigate the survival outcomes for non-Hodgkin lymphoma (NHL) in HIV-infected vs. -uninfected patients from the same integrated health care system, and to identify prognostic factors for HIV-related NHL in the era of combined antiretroviral therapy (cART).
Incident NHL diagnosed between 1996–2005 were identified from members of Kaiser Permanente (KP) California Health Plans. Two-year all-cause and lymphoma-specific mortality by HIV status were examined using multivariable Poisson regression. Among HIV-infected patients, prognostic factors of demographics, lymphoma- and HIV-related characteristics for the same outcomes were also examined.
A total of 259 HIV-infected and 8,230 HIV-uninfected incident NHL cases were evaluated. Fifty-nine percent of HIV-infected patients died within 2 years after NHL diagnosis, compared to 30% of HIV-uninfected patients. HIV status was independently associated with a doubling of 2-year all-cause mortality (Relative Risk=2.0, 95% Confidence Interval=1.7–2.3). This elevated mortality risk for HIV-infected patients was similar for all race groups, lymphoma stages and histologic subtypes. HIV-infected patients with CD4 cell count <200/mm3 and/or prior AIDS-defining illness were also at increased risk for lymphoma-specific mortality compared to HIV-uninfected patients. Among HIV-infected NHL cases, significant prognostic factors for overall mortality included prior AIDS-defining illness and Burkitt’s subtype.
HIV-infected patients with NHL in the cART era continue to endure substantially higher mortality compared with HIV-uninfected patients with NHL. Better management and therapeutic approaches to extend survival time for HIV-related NHL are needed.
HIV infection; non-Hodgkin lymphoma; prognostic factors; antiretroviral therapy; mortality
Numerous studies have reported positive associations of environmental exposure to polychlorinated biphenyls (PCBs) and p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) with the risk of non-Hodgkin lymphoma (NHL). In a case-control study nested within the Nurses’ Health Study, a prospective cohort of US women, we measured concentrations of PCBs and p,p′-DDE in blood samples from 145 women diagnosed with NHL at least six months after blood draw, and 290 age- and race-matched controls. We used conditional logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for each quartile of exposure relative to the lowest quartile. We also evaluated these associations for major histologic subtypes of NHL. There was no consistent evidence of an association of p,p′-DDE, total PCBs, immunotoxic or individual PCB congeners with risk of NHL. These results do not support the hypothesis of a positive association between PCB exposure and development of NHL.
organochlorine; polychlorinated biphenyl; PCB; DDT; non-Hodgkin lymphoma
Prospective studies of lifestyle and non-Hodgkin lymphoma (NHL) are conflicting, and some are inconsistent with case-control studies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was used to evaluate risk of NHL and its subtypes in association with anthropometric factors, smoking, and alcohol consumption in a prospective cohort study. Lifestyle was assessed via questionnaire among 142,982 male and female participants aged 55–74 years enrolled in the PLCO Trial during 1993–2001. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards regression. During 1,201,074 person-years of follow-up through 2006, 1,264 histologically confirmed NHL cases were identified. Higher body mass index (BMI; weight (kg)/height (m)2) at ages 20 and 50 years and at baseline was associated with increased NHL risk (Ptrend < 0.01 for all; e.g., for baseline BMI ≥30 vs. 18.5–24.9, hazard ratio = 1.32, 95% confidence interval: 1.13, 1.54). Smoking was not associated with NHL overall but was inversely associated with follicular lymphoma (ever smoking vs. never: hazard ratio = 0.62, 95% confidence interval: 0.45, 0.85). Alcohol consumption was unrelated to NHL (drinks/week: Ptrend = 0.187). These data support previous studies suggesting that BMI is positively associated with NHL, show an inverse association between smoking and follicular lymphoma (perhaps due to residual confounding), and do not support a causal association between alcohol and NHL.
alcoholic beverages; anthropometry; body height; body mass index; body weight; life style; lymphoma; non-Hodgkin; smoking
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.
cohort studies; lymphoma, non-Hodgkin; smoking; tobacco smoke pollution
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.
case-control studies; contraception; estrogens; hormone replacement therapy; lymphoma, non-Hodgkin; menopause; pregnancy; reproduction
Polymorphisms in chemokine genes have been associated with human immunodeficiency virus (HIV)-related non-Hodgkin lymphoma (NHL) but are understudied in non-HIV-related NHL. Associations of NHL and NHL subtypes with polymorphisms and haplotypes in CCR5, CCR2, CCL5, CXCL12 and CX3CR1 were explored in a pooled analysis of three case-control studies (San Francisco Bay Area, California; United Kingdom; total: cases N=1610, controls N=1992). Adjusted unconditional logistic regression was used to estimate relative risks among HIV-negative non-Hispanic Caucasians. The CCR5M Δ32 deletion reduced the risk of NHL (odds ratio=0.56, 95% confidence interval=0.38-0.83) in men but not women with similar effects observed for diffuse large-cell and follicular lymphoma (FL). NHL risk also was reduced in men with the CCR2/CCR5 haplotype characterized by the CCR5 Δ32 deletion. The CCL5 −403A allele conferred reduced risks of FL and chronic lymphocytic leukemia/small lymphocytic lymphoma. Results should be interpreted conservatively. Continued investigation is warranted to confirm these findings.
Lymphoma non-Hodgkin; Chemokines; Polymorphism, genetic; Case-Control
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.
non-Hodgkin's lymphoma; family history; haematopoietic malignancy; lymphoma; leukaemia
Case-control studies suggest increased sun exposure reduces non-Hodgkin lymphoma (NHL) risk. Evidence from prospective cohort studies, however, is limited and inconsistent. We evaluated the association between ambient ultraviolet radiation (UV) exposure and NHL in a nationwide cohort of women, the Nurses’ Health Study (NHS).
Between 1976 and 2006, we identified 1064 incident NHL cases among 115,482 women in the prospective NHS. Exposures assessed included average annual UV-B flux based on residence at various times during life, vitamin D intake, and predicted plasma 25-hydroxyvitamin D levels. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) for risk of all NHL and histologic subtypes using Cox proportional hazards models.
NHL risk was increased for women residing in areas of high ambient UV radiation (UV-B flux >113 R-B count × 10−4) compared to those with lower exposure (<113), with positive linear trends at all time points. The multivariable-adjusted RR for high UV area at age 15 was 1.21 (95% CI: 1.00, 1.47; p-trend <0.01). There was no evidence of statistical heterogeneity by subtype, although power was limited for subtype analyses. We observed no association between vitamin D measures and risk of NHL overall or by subtype.
Our findings do not support the hypothesis of a protective effect of UV radiation exposure on NHL risk. We found no association between vitamin D and NHL risk.
non-Hodgkin lymphoma; sunlight; ultraviolet radiation; vitamin D; epidemiology
Investigating the relationship between occupational exposure to pesticides and the risk of lymphoid neoplasms (LN) in men.
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.
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.
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.
Adolescent; Adult; Aged; Case-Control Studies; Employment; statistics & numerical data; France; epidemiology; Fungicides, Industrial; toxicity; Herbicides; toxicity; Hodgkin Disease; chemically induced; epidemiology; Humans; Insecticides; toxicity; Leukemia, Hairy Cell; chemically induced; epidemiology; Lymphoma; chemically induced; epidemiology; Lymphoma, Non-Hodgkin; chemically induced; epidemiology; Male; Middle Aged; Multiple Myeloma; chemically induced; epidemiology; Occupational Diseases; chemically induced; epidemiology; Occupational Exposure; adverse effects; statistics & numerical data; Pesticides; toxicity; Young Adult; occupation; pesticides; farming; lymphoma; epidemiology.
Lymphoid neoplasms (LN), including non-Hodgkin’s lymphoma (NHL), Hodgkin’s lymphoma (HL), lymphoproliferative syndrome (LPS) and multiple myeloma (MM), are among the most frequent cancers (approximately 17,000 new cases per year in France), after those related to smoking. LN were investigated using the data from the ENGELA study. ENGELA is a multicenter hospital-based case-control study that was carried out in France over the period September 2000 – December2004. In all, 822 cases (397 NHL, 149 LH, 168 SLP and 108 MM) and 752 controls were included and described 5481 and 5188 first degree relatives, respectively. A positive association with a familial history of hematopoietic cancer was observed for LN (OR = 1.7 [1.0–2.8]) overall and for LPS (OR = 3.2 [1.4–6.8]). The associations with HL (OR = 10.4 [2.0–53.8]) and NHL (OR = 2.4 [1.0–5.9]) were stronger for men. The associations were also stronger when the disease had been diagnosed before the relatives were aged 45 years. The results mainly support the involvement of genetic factors and suggest that at least some of those factors may be sex-linked. However, the slight overrepresentation of affected spouses among the cases might also support the responsibility of environmental factors.
Adult; Aged; Case-Control Studies; Family; Female; Humans; Incidence; Leukemia; epidemiology; etiology; genetics; Lymphoma; epidemiology; etiology; genetics; Lymphoproliferative Disorders; genetics; Male; Middle Aged; Multiple Myeloma; genetics; epidemiology; lymphoid neoplasm; family; aetiology