Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

The association between selected risk factors for pancreatic cancer and the expression of p53 and K-ras codon 12 mutations.

Background: Pancreatic cancer is a major contributor to cancer mortality. Studies suggest that a few risk factors, including cigarette smoking, body mass index, having a relative with pancreatic cancer, and diabetes may be related to pancreatic cancer risk.

Aim Of The Study: We conducted a case-control study in southeastern Michigan to examine the relation between the above mentioned risk factors and mutations of the K-ras oncogene and p53 tumor suppressor gene.

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.

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.

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.

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.

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.

Exploring physician and staff perceptions of the learning environment in ambulatory residency clinics.

Background And Objectives: Investigations of teaching quality in ambulatory clinics have generally focused on faculty and medical student perspectives. We investigated the association of learning and organizational environment variables with faculty, resident, and nursing staff perceptions of quality of teaching and with a measure of resident learning in ambulatory residency clinics.

Methods: Annually over 5 years (1998-2002), we distributed learning and organizational environment surveys to faculty, residents, and staff in three ambulatory clinics of the Wayne State University Department of Family Medicine.

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

We previously reported that, although asthma did not increase the risk of non-Hodgkin's lymphoma (NHL), the risk from pesticide exposures was higher among asthmatics than that among nonasthmatics. To further evaluate this finding, we analyzed data from a population-based case-control study of NHL conducted in Iowa, Detroit, Los Angeles and Seattle. Cases (n = 668) diagnosed with NHL from 1998 to 2000 and controls (n = 543) randomly selected from the same geographical areas as that of the cases were included in this analysis.

Absenteeism from work: the experience of employed breast and prostate cancer patients in the months following diagnosis.

Background: A better understanding of how cancer treatments affect patient's employment may help patients and physicians make more informed choices between treatment alternatives. This study examined the number of days employed patients undergoing treatment for either breast or prostate cancer were absent from their jobs.

Method: Using the Detroit Surveillance, Epidemiology, End-Results registry, all potentially eligible women diagnosed with breast cancer and men diagnosed with prostate cancer were selected.