New American Cancer Society process for creating trustworthy cancer screening guidelines.

Guidelines for cancer screening written by different organizations often differ, even when they are based on the same evidence. Those dissimilarities can create confusion among health care professionals, the general public, and policy makers. The Institute of Medicine (IOM) recently released 2 reports to establish new standards for developing more trustworthy clinical practice guidelines and conducting systematic evidence reviews that serve as their basis. Because the American Cancer Society (ACS) is an important source of guidance about cancer screening for both health care practitioners and the general public, it has revised its methods to create a more transparent, consistent, and rigorous process for developing and communicating guidelines. The new ACS methods align with the IOM principles for trustworthy clinical guideline development by creating a single generalist group for writing the guidelines, commissioning independent systematic evidence reviews, and clearly articulating the benefits, limitations, and harms associated with a screening test. This new process should ensure that ACS cancer screening guidelines will continue to be a trustworthy source of information for both health care practitioners and the general public to guide clinical practice, personal choice, and public policy about cancer screening.

A case-control study of occupational exposure to trichloroethylene and non-Hodgkin lymphoma.

BACKGROUND: Previous epidemiologic findings suggest an association between exposure to trichloroethylene (TCE), a chlorinated solvent primarily used for vapor degreasing of metal parts, and non-Hodgkin lymphoma (NHL). OBJECTIVES: We investigated the association between occupational TCE exposure and NHL within a population-based case-control study using detailed exposure assessment methods. METHODS: Cases (n = 1,189; 76% participation rate) and controls (n = 982; 52% participation rate) provided information on their occupational histories and, for selected occupations, on possible workplace exposure to TCE using job-specific interview modules. An industrial hygienist assessed potential TCE exposure based on this information and a review of the TCE industrial hygiene literature. We computed odds ratios (ORs) and 95% confidence intervals (CIs) relating NHL and different metrics of estimated TCE exposure, categorized using tertiles among exposed controls, with unexposed subjects as the reference group. RESULTS: We observed associations with NHL for the highest tertiles of estimated average weekly exposure (23 exposed cases; OR = 2.5; 95% CI, 1.1­6.1) and cumulative exposure (24 exposed cases; OR = 2.3; 95% CI, 1.0-5.0) to TCE. Tests for trend with these metrics surpassed or approached statistical significance (p-value for trend = 0.02 and 0.08, respectively); however, we did not observe dose­response relationships across the exposure levels. Overall, neither duration nor intensity of exposure was associated with NHL, although we observed an association with the lowest tertile of exposure duration (OR = 2.1; 95% CI, 1.0-4.7). CONCLUSIONS: Our findings offer additional support for an association between high levels of exposure to TCE and increased risk of NHL. However, we cannot rule out the possibility of confounding from other chlorinated solvents used for vapor degreasing and note that our exposure assessment methods have not been validated.

Genetic variation in Th1/Th2 pathway genes and risk of non-Hodgkin lymphoma: a pooled analysis of three population-based case-control studies.

The balance between T-helper 1 (Th1) and T-helper 2 (Th2) activity is critical in lymphoid cell development and differentiation. Immune dysfunction underlies lymphomagenesis, so an alteration in the regulation of key Th1/Th2 cytokines may lead to the development of non-Hodgkin lymphoma (NHL). To study the impact of polymorphisms in Th1/Th2 cytokines on NHL risk, we analyzed 145 tag single nucleotide polymorphisms (SNPs) in 17 Th1/Th2 cytokine and related genes in three population-based case-control studies (1946 cases and 1808 controls). Logistic regression was used to compute odds ratios (OR) for NHL and four major NHL subtypes in relation to tag SNP genotypes and haplotypes. A gene-based analysis adjusting for the number of tag SNPs genotyped in each gene showed significant associations with risk of NHL combined and one or more NHL subtypes for Th1 (IL12A and IL12RB1) and Th2 (IL4, IL10RB, and IL18) genes. The strongest association was for rs485497 in IL12A, which plays a central role in bridging the cellular and humoral pathways of innate resistance and antigen-specific adaptive immune responses (allele risk OR= 1·17; P(trend)= 0·00099). This SNP was also associated specifically with risk of follicular lymphoma (allele risk OR= 1·26; P(trend)= 0·0012). These findings suggest that genetic variation in Th1/Th2 cytokine genes may contribute to lymphomagenesis.

A pooled analysis of three studies evaluating genetic variation in innate immunity genes and non-Hodgkin lymphoma risk.

Genetic variation in immune-related genes may play a role in the development of non-Hodgkin lymphoma (NHL). To test the hypothesis that innate immunity polymorphisms may be associated with NHL risk, we genotyped 144 tag single nucleotide polymorphisms (tagSNPs) capturing common genetic variation within 12 innate immunity gene regions in three independent population-based case-control studies (1946 cases and 1808 controls). Gene-based analyses found IL1RN to be associated with NHL risk (minP = 0·03); specifically, IL1RN rs2637988 was associated with an increased risk of NHL (per-allele odds ratio = 1·15, 95% confidence interval = 1·05-1·27; P(trend) = 0·003), which was consistent across study, subtype, and gender. FCGR2A was also associated with a decreased risk of the follicular lymphoma NHL subtype (minP = 0·03). Our findings suggest that genetic variation in IL1RN and FCGR2A may play a role in lymphomagenesis. Given that conflicting results have been reported regarding the association between IL1RN SNPs and NHL risk, a larger number of innate immunity genes with sufficient genomic coverage should be evaluated systematically across many studies.

Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32.

To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).

Work task disability in employed breast and prostate cancer patients.

INTRODUCTION: Nearly 60% of cancer survivors are of working age, making inquiries into work-related disabilities particularly relevant. This paper describes work-related physical and cognitive disability estimates 12 and 18 months after diagnosis and treatment in a sample of employed breast and prostate cancer patients. METHODS: We recruited employed, newly diagnosed patients (n=447 breast, n=267 prostate) from the Metropolitan Detroit Cancer Surveillance System for telephone interviews 12 and 18 months after diagnosis. We defined disability by work task activity limitation. Disability estimates and employment were compared using Pearson chi-square tests. Duration of hours worked was compared by disability status using t-tests. RESULTS: Approximately 60% of women reported physical disability at 12 months which decreased to 36% at 18 months. Cognitive disability was reported by 34% and 22% of women at 12 and 18 months, respectively. Fewer men reported physical disability, only 29% at 12 months, decreasing to 17% at 18 months. Cognitive disability was reported by 12% and 7% of men at 12 and 18 months, respectively. More individuals with disability left the workforce at each timeframe than those without disability. CONCLUSIONS: A significant proportion of breast and prostate cancer patients experienced work-related disabilities 1 year or more following treatment. Physical disability was more problematic than cognitive disability.

Incorporating Geographic Information Systems (GIS) into program evaluation: lessons from a rural medicine initiative.

PURPOSE: To address the shortage of physicians practicing in rural areas of Michigan, the Wayne State University School of Medicine developed an integrated rural core curriculum to interest students in rural practice careers. Here we focus on the evaluation strategy used to determine the extent to which students in the new rural medicine interest group who self-identified as selecting a rural clerkship or externship did secure a clinical training experience in a rural setting. METHODS: Three measures of rurality were compared to determine whether students were placed in rural training settings: (1) the percentage of the county living in rural areas; (2) a county-level dichotomous measure of rural/nonrural; and (3) a dichotomous measure based on urban area boundaries within the county. Practice address and geographic data were integrated into geographic information systems software, which we used to map out rural characteristics of Michigan counties through a process called thematic mapping; this shows characteristic variation by color-shading geographic features. In addition, reference maps were created showing the boundaries of urban areas and metropolitan/micropolitan areas. Once these processes were completed, we overlaid the practice location on the contextual-level geographic features to produce a visual representation of the relationship between student placement and rural areas throughout the state. RESULTS: The outcome of student placement in rural practices varied by the definition of rural. We concluded that, although students were not placed in the most rural areas of Michigan, they received clerkship or externship training near rural areas or in semirural areas. CONCLUSION: This process evaluation had a direct impact on program management by highlighting gaps in preceptor recruitment. A greater effort is being made to recruit physicians for more rural areas of the state rather than urban and semirural areas. Geographic information systems mapping also defined levels of ruralism for students to help them make informed selections of training sties. This is especially important for students who are not sure about a rural experience and might be discouraged by placement in a remote rural area.

Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium.

In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF -308G>A (rs1800629), lymphotoxin-alpha (LTA) 252A>G (rs909253), IL10 -3575T>A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for "new" participant TNF -308A carriers (NHL: per-allele odds ratio (OR(allelic)) = 1.10, P(trend) = 0.001; diffuse large B-cell lymphoma (DLBCL): OR(allelic) = 1.23, P(trend) = 0.004). In the combined population, odds ratios were increased for TNF -308A carriers (NHL: OR(allelic) = 1.13, P(trend) = 0.0001; DLBCL: OR(allelic) = 1.25, P(trend) = 3.7 x 10(-6); marginal zone lymphoma: OR(allelic) = 1.35, P(trend) = 0.004) and LTA 252G carriers (DLBCL: OR(allelic) = 1.12, P(trend) = 0.006; mycosis fungoides: OR(allelic) = 1.44, P(trend) = 0.015). The LTA 252A>G/TNF -308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 x 10(-8)). Results suggested associations between IL10 -3575T>A and DLBCL (P(trend) = 0.02) and IL10 -1082A>G and mantle cell lymphoma (P(trend) = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A>G/TNF -308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology.

Breast and prostate cancer patient's reliability of treatment reporting.

PURPOSE: To compare patient reported cancer treatments with data obtained by trained abstractors in the Metropolitan Detroit Cancer Surveillance System (MDCSS) to assess the reliability of patient interviews as a source for cancer treatments. METHODS: Patients (n=492 breast patients and n=291 prostate patients) were identified from the MDCSS and interviewed approximately 6 months after initial diagnosis for receipt of cancer treatment. Kappa statistics compared agreement between patient's report of their treatments and the MDCSS. RESULTS: Breast cancer patients had moderate levels of agreement regarding receipt of chemotherapy and radiation and excellent agreement for surgery. In contrast, prostate cancer patients and registry reports achieved excellent concordance for radiation therapy, very good agreement for surgery, and moderate levels of agreement for hormone therapy. Sensitivity of chemotherapy, surgery, and radiation reporting exceeded 90% for both patient cohorts. Overall, patients reported more treatment than was recorded i n M DCSS. CONCLUSION: Patients can be reliabledata sources for medical information pertaining to cancer therapies, although recall may vary by treatment type and time since treatment. Protocols involving patient interviews may wish to consider these encounters as timely, reliable data source options.

Genetic variation in caspase genes and risk of non-Hodgkin lymphoma: a pooled analysis of 3 population-based case-control studies.

Caspases play a critical role in regulation of apoptosis, cell differentiation, inflammation, and innate immunity, and several are mutated or have altered expression in non-Hodgkin lymphoma (NHL). To study the impact of genetic variation in caspases on NHL risk, we analyzed tag single nucleotide polymorphisms (SNPs) in 12 caspase and related genes in 3 population-based case-control studies (1946 cases and 1808 controls). Gene-based analysis, adjusting for the number of tagSNPs genotyped in each gene, showed significant associations for CASP8, CASP9, and CASP1. SNP-based analysis showed that CASP8 rs6736233 (odds ratio (OR) (CG) = 1.21; OR(CC) = 2.13; P trend = .011); CASP9 rs4661636 (OR(CT) = 0.89; OR(TT) = 0.77; P trend = .011); and CASP1 rs1785882 (OR(AT) = 1.12; OR(AA) = 1.30; P trend = .0054) were significantly associated with NHL risk and consistent across studies. It is noteworthy that genetic variants in CASP8 were associated with risk of all major NHL subtypes. Our findings suggest that genetic variation in caspases may play an important role in lymphomagenesis.

Etiologic heterogeneity among non-Hodgkin lymphoma subtypes.

Understanding patterns of etiologic commonality and heterogeneity for non-Hodgkin lymphomas may illuminate lymphomagenesis. We present the first systematic comparison of risks by lymphoma subtype for a broad range of putative risk factors in a population-based case-control study, including diffuse large B-cell (DLBCL; N = 416), follicular (N = 318), and marginal zone lymphomas (N = 106), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; N = 133). We required at least 2 of 3 analyses to support differences in risk: (1) polytomous logistic regression, (2) homogeneity tests, or (3) dichotomous logistic regression, analyzing all 7 possible pairwise comparisons among the subtypes, corresponding to various groupings by clinical behavior, genetic features, and differentiation. Late birth order and high body mass index (>/= 35) kg/m(2)) increased risk for DLBCL alone. Autoimmune conditions increased risk for marginal zone lymphoma alone. The tumor necrosis factor G-308A polymorphism (rs1800629) increased risks for both DLBCL and marginal zone lymphoma. Exposure to certain dietary heterocyclic amines from meat consumption increased risk for CLL/SLL alone. We observed no significant risk factors for follicular lymphoma alone. These data clearly support both etiologic commonality and heterogeneity for lymphoma subtypes, suggesting that immune dysfunction is of greater etiologic importance for DLBCL and marginal zone lymphoma than for CLL/SLL and follicular lymphoma.

Dietary flavonoid intake and non-Hodgkin lymphoma risk.

BACKGROUND: The role of dietary factors in non-Hodgkin lymphoma (NHL) risk is not yet well understood. Dietary flavonoids are polyphenolic compounds proposed to be anticarcinogenic. Flavonoids are well-characterized antioxidants and metal chelators, and certain flavonoids exhibit antiproliferative and antiestrogenic effects. OBJECTIVE: We aimed to evaluate the hypothesis that higher flavonoid intake is associated with lower NHL risk. DESIGN: During 1998-2000, we identified incident NHL cases aged 20-74 y from 4 US Surveillance, Epidemiology, and End Results cancer registries. Controls without history of NHL were selected by random-digit dialing or from Medicare files and frequency-matched to cases by age, center, race, and sex. Using 3 recently developed US Department of Agriculture nutrient-specific databases, flavonoid intake was estimated from participant responses to a 117-item food-frequency questionnaire (n = 466 cases and 390 controls). NHL risk in relation to flavonoid intake in quartiles was evaluated after adjustment for age, sex, registry, education, NHL family history, and energy intake. RESULTS: Higher total flavonoid intake was significantly associated with lower risk of NHL (P for trend < 0.01): a 47% lower risk in the highest quartile of intake than in the lowest (95% CI: 31%, 73%). Higher intakes of flavonols, epicatechins, anthocyanidins, and proanthocyanidins were each significantly associated with decreased NHL risk. Similar patterns of risk were observed for the major NHL subtypes--diffuse large B-cell lymphoma (n = 167) and follicular lymphoma (n = 146). CONCLUSION: A higher intake of flavonoids, dietary components with several putative anticarcinogenic activities, may be associated with lower NHL risk.

Vegetables- and antioxidant-related nutrients, genetic susceptibility, and non-Hodgkin lymphoma risk.

Genetic susceptibility to DNA oxidation, carcinogen metabolism, and altered DNA repair may increase non-Hodgkin lymphoma (NHL) risk, whereas vegetables- and antioxidant-related nutrients may decrease risk. We evaluated the interaction of a priori-defined dietary factors with 28 polymorphisms in these metabolic pathways. Incident cases (n = 1,141) were identified during 1998-2000 from four cancer registries and frequency-matched to population-based controls (n = 949). We estimated diet-gene joint effects using two-phase semi-parametric maximum-likelihood methods, which utilized genotype data from all subjects as well as 371 cases and 311 controls with available diet information. Adjusted odds ratios (95% confidence intervals) were lower among common allele carriers with higher dietary intakes. For the GSTM3 3-base insertion and higher total vegetable intake, the risk was 0.56 (0.35-0.92, p interaction = 0.03); for GSTP1 A114V and higher cruciferous vegetable intake, the risk was 0.52 (0.34-0.81, p interaction = 0.02); for OGG1 S326C and higher daily zinc intake, the risk was 0.71 (0.47-1.08, p interaction = 0.04) and for XRCC3 T241M and higher green leafy vegetable intake, the risk was 0.63 (0.41-0.97, p interaction = 0.03). Calculation of the false positive report probability determined a high likelihood of falsely positive associations. Although most associations have not been examined previously with NHL, our results suggest the examined polymorphisms are not modifiers of the association between vegetable and zinc intakes and NHL risk.

Employment and cancer: findings from a longitudinal study of breast and prostate cancer survivors.

We discuss how cancer affected the employment of almost 800 employed patients who participated in a longitudinal study. The greatest reduction in patients' labor supply (defined as employment and weekly hours worked) was observed 6 months following diagnosis. At 12 and 18 months following diagnosis, many patients returned to work. Based on these and other findings related to patients' employment situations, we suggest 4 areas for future research: 1) collection of employment information in cancer studies; 2) research into racial and ethnic minority patients and employment outcomes; 3) interventions to reduce the effects of cancer and its treatment on employment; and 4) investigations into the influence of employment-contingent health insurance on cancer treatment and recovery.

Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER case-control study.

We previously reported a lower risk of non-Hodgkin lymphoma (NHL) associated with high consumption of vitamin B6 and methionine, dietary determinants of one-carbon metabolism. Evidence has linked genetic variants involved in one-carbon metabolism to NHL. We investigated 30 polymorphisms in 18 genes for their main effect on NHL among 1141 incident cases and 949 population-based controls and examined gene-nutrient interactions in a subgroup of 386 cases and 319 controls who provided detailed food-frequency information. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for age, sex, and race. We observed a decreased risk of NHL over-all with BHMTEx8+453A>T and increased risk with CBS Ex13+41C>T, FPGS Ex15-263T>C, and SHMT1 Ex12+138C>T and Ex12+236C>T. Furthermore, significant gene-nutrient interactions limited the protective association comparing high versus low vitamin B6 to FPGS Ex15-263T>C CC (OR = 0.22; 95% CL = 0.10-0.52), MTHFS IVS2-1411T>G TT/TG (OR = 0.54; 95% CI = 0.36-0.81), and MTR Ex26-20A>G AA (OR = 0.55; 95% CI = 0.35-0.86) genotypes, and the protective association of methionine to FTHFD Ex10-40G>TGG (OR = 0.63; 95% CI = 0.44-0.91), MTHFR Ex8-62A>C CC (OR = 0.13; 95% CI = 0.04-0.39), and MTRR Ex5+136T>CTT (OR = 0.67; 95% CI = 0.47-0.97) genotypes. Warranting replication, our finding of gene-nutrient interactions in one-carbon metabolism supports their etiologic involvement in lymphomagenesis.

Risk of other cancers in individuals with a family history of pancreas cancer.

BACKGROUND: Inherited predisposition to pancreas cancer accounts for approximately 10% of cases. Familial aggregation may be influenced by shared environmental factors and shared genes. We evaluate whether a family history of pancreas cancer is a risk factor for ten specified cancers in first-degree relatives: bladder, breast, colon, head and neck, lung, lymphoma, melanoma, ovary, pancreas, and prostate. METHODS: Risk factor data and cancer family history were obtained for 1,816 first-degree relatives of pancreas cancer case probands (n = 247) and 3,157 first-degree relatives of control probands (n = 420). Unconditional logistic regression models using generalized estimating equations were used to estimate odds ratios (ORs), and 95% confidence intervals of having a first-degree relative a specified cancer. RESULTS: A family history of pancreas cancer was associated with a doubled risk of lymphoma (OR = 2.83, 95% CI = 1.02-7.86) and ovarian cancer (OR = 2.25, 95% CI = 0.77-6.60) among relatives after adjustment. Relatives with a family history of early-onset pancreas cancer in a proband had a sevenfold increased risk of lymphoma (OR = 7.31, 95% CI = 1.45 to 36.7). Relatives who ever smoked and had a family history of pancreas cancer had a fivefold increased risk of ovarian cancer (OR = 4.89, 95% CI = 1.16-20.6). CONCLUSION: Family history assessment of cancer risk should include all cancers. Assessment of other known and suspected risk factors in relatives will improve risk evaluation. As screening and surveillance methods are developed, identifying those at highest risk is crucial for a successful screening program.

Genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2) and risk of non-Hodgkin lymphoma.

Animal studies suggest that lymphomagenesis can be induced by exposure to carcinogenic aromatic and heterocyclic amines found in diet, cigarette smoke and the environment, but human epidemiologic investigations of these exogenous exposures have yielded conflicting results. As part of our evaluation of the role of aromatic and heterocyclic amines, which are metabolized by N-acetyltransferase (NAT) enzymes, in the etiology of non-Hodgkin lymphoma (NHL), we examined NHL risk in relation to genetic variation in NAT1 and NAT2 and exposure to cigarette smoke and dietary heterocyclic amines and mutagens. We genotyped 10 common single nucleotide polymorphisms (SNPs) in NAT1 and NAT2 among 1136 cases and 922 controls from a population-based case-control study in four geographical areas of the USA. Relative risk of NHL for NAT1 and NAT2 genotypes, NAT2 acetylation phenotype, and exposure to cigarette smoke and dietary heterocyclic amines and mutagens was estimated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from unconditional logistic regression models. We observed increased risk of NHL among individuals with the NAT1*10/*10 genotype compared with individuals with other NAT1 genotypes (OR = 1.60, 95% CI = 1.04-2.46, P = 0.03). We also observed increased NHL risk in a dose-dependent model among NAT2 intermediate- and rapid-acetylators compared with slow-acetylators, although only the trend was statistically significant (intermediate: OR = 1.18, 95% CI = 0.97-1.44, P = 0.1; rapid: OR = 1.43, 95% CI = 0.97-2.14, P = 0.07; P for linear trend = 0.03). Compared with non-smokers, NHL risk estimates for current cigarette smoking were increased only among NAT2 intermediate/rapid-acetylators (OR = 2.44, 95% CI = 1.15-5.20, P = 0.02). Our data provide evidence that NAT1 and NAT2 genotypes are associated with NHL risk and support a contributory role for carcinogenic aromatic and/or heterocyclic amines in the multi-factorial etiology of NHL.

Vegetables, fruit, and antioxidant-related nutrients and risk of non-Hodgkin lymphoma: a National Cancer Institute-Surveillance, Epidemiology, and End Results population-based case-control study.

BACKGROUND: Factors related to DNA damage and altered immunologic responses, such as reactive oxygen species production, are associated with the risk of non-Hodgkin lymphoma (NHL). OBJECTIVE: The aim was to evaluate NHL risk with intakes of vegetables, fruit, and nutrients involved in antioxidant activities. DESIGN: Incident case subjects aged 20-74 y were identified between 1998 and 2000 from a National Cancer Institute-sponsored study by using four Surveillance, Epidemiology, and End Results registries. Control subjects, who were selected by random dialing (< 65 y) and from Medicare files (> or = 65 y), were matched to cases by age, center, race, and sex. Of 1321 case and 1057 control subjects who enrolled, dietary data were collected on a subset (466 cases and 391 controls). Carotenoid intakes were estimated by using updated values from the US Department of Agriculture nutrient databases. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% CIs. RESULTS: NHL risk was inversely associated with higher number of weekly servings of all vegetables (multivariable OR for highest compared with lowest quartile: 0.58; 95% CI: 0.35, 0.95; P for trend = 0.04), green leafy vegetables (OR: 0.59; 95% CI: 0.36, 0.96; P for trend = 0.01), and cruciferous vegetables (OR: 0.62; 95% CI: 0.39, 1.00; P for trend = 0.05) and with higher daily intakes of lutein and zeaxanthin (OR: 0.54; 95% CI: 0.32, 0.91; P for trend = 0.06) and zinc (OR: 0.58; 95% CI: 0.36, 0.91; P for trend = 0.02). An effect modification by exercise and NHL subtype was observed with some food groups and nutrients. CONCLUSION: Higher intakes of vegetables, lutein and zeaxanthin, and zinc are associated with a lower NHL risk.