Kenneth P. Cantor

A case-control study of non-Hodgkin's lymphoma and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in eastern Nebraska.

To evaluate the role of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in the development of non-Hodgkins lymphoma (NHL), we conducted a population-based, case-control study in 66 counties in eastern Nebraska. Telephone interviews were conducted with 201 white men diagnosed with NHL between July 1, 1983, and June 30, 1986, and with 725 controls. There was a 50% excess of NHL among men who mixed or applied 2,4-D (odds ratio [OR] = 1.5; 95% confidence interval = 0.9, 2.5). The risk of NHL increased with the average frequency of use to over threefold for those exposed 20 or more days per year (p for trend = 0.051). Adjusting for use of organophosphate insecticides lowered the risk estimate for frequent users (OR = 1.8), but adjustment for fungicide use increased the risk estimate (OR = 4.5). Simultaneous adjustment for organophosphates and fungicides yielded an OR of 3.1 for farmers who mixed or applied 2,4-D more than 20 days per year. Risk also increased with degree of exposure, as indicated by application method and time spent in contaminated clothing, but not with the number of years of 2,4-D use or failure to use protective equipment. Although other pesticides, especially organophosphate insecticides, may be related to NHL, the risk associated with 2,4-D does not appear to be explained completely by these other exposures

Dietary factors and non-Hodgkin's lymphoma in Nebraska (United States)

Little is known about dietary factors and non-Hodgkins lymphoma (NHL) risk, although high intakes of animal protein and milk have been associated with NHL in two previous studies. As part of a population-based case-control study of agricultural and other risk factors for NHL in eastern Nebraska (USA), we examined the self- and proxy-reported frequency of consumption of 30 food items by 385 White men and women with NHL and 1,432 controls. Animal protein intake was not associated significantly with the risk of NHL, however, there was a nonsignificatly elevated risk of NHL among men with high milk consumption. Vitamin C, carotene, citrus fruit, and dark green vegetable intakes were inversely significantly related to the risk of NHL for men, but not for women. Among men, the odds ratios for the highest quartiles of both vitamin C and carotene intake were 0.6 (95% confidence intervals=0.3–1.0). There were no meaningful fifferences in the associations of nutrientintakes and NHL, risk between B- and T-cell lymphomas and histologic types. Risks for low intakes of vitamin C and carotene were greater among men and women with a family history of cancer, particularly a history of lymphatic or hematopoietic cancer among first-degree relatives.

Etiologic Heterogeneity Among Non-Hodgkin Lymphoma Subtypes: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

BACKGROUNDnNon-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes.nnnMETHODSnWe pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case-control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P NODE).nnnRESULTSnRisks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P NODE < 1.0×10(-4)), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P NODE < 1.0×10(-4)). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a teacher generally were restricted to marginal zone lymphoma, Burkitt/Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma, and/or lymphoplasmacytic lymphoma/Waldenström macroglobulinemia.nnnCONCLUSIONSnUsing a novel approach to investigate etiologic heterogeneity among NHL subtypes, we identified risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes, suggesting both subtype-specific and shared underlying mechanisms. Further research is needed to test putative mechanisms, investigate other risk factors (eg, other infections, environmental exposures, and diet), and evaluate potential joint effects with genetic susceptibility.

Polychlorinated biphenyl levels in peripheral blood and non-Hodgkin's lymphoma : A report from three cohorts

The incidence of non-Hodgkins lymphoma (NHL) unrelated to HIV infection has steadily increased over the past several decades and remains substantially unexplained. Limited evidence suggests that increased concentrations of polychlorinated biphenyls (PCB) measured in blood or fat tissue are associated with increased risk of NHL. Although PCB congeners vary in their biological activity, the relation between individual congeners and NHL risk has not been examined previously using prospectively collected biospecimens. We examined congener-specific associations in three prospective cohorts. Prediagnostic serum or plasma concentrations of selected PCB congeners were measured among NHL cases and controls from these cohorts: Janus (190 cases and 190 controls) in Norway and CLUE I (74 cases and 147 controls) and the Nurses Health Study (30 cases and 78 controls) in the United States. All blood samples were collected in the 1970s or 1980s. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the relations between risk of NHL and lipid-corrected plasma or serum concentrations. Several congeners (i.e., 118, 138, and 153) that were present at higher levels and were moderately to highly correlated with each other showed exposure-response trends with risk of NHL in all three cohorts. These associations were observed primarily among subjects diagnosed closer to the date of blood collection in the two cohorts with sufficient cases to permit stratification by time. Among cases diagnosed within the median years of follow-up (16 years in Janus and 12 years in CLUE I), ORs and 95% CIs for increasing fourths of concentration of congener 118 relative to the lowest fourth were as follows: 2.4 (0.9-6.5), 4.9 (1.6-15.3), and 5.3 (1.5-18.8; P(trend) < 0.005) in Janus and 8.1 (1.0-68.9), 6.6 (0.7-59.0), and 13.0 (1.6-106.8; P(trend) < 0.05) in CLUE I. Similar patterns were seen for congeners 138 and 153 and for total PCBs. Limited evidence of exposure-response trends was also observed for several other congeners. The primary 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane metabolite, p,p-DDE, was not significantly associated with NHL in most analyses but slightly to moderately confounded the PCB associations. The results from these three cohorts suggest that concentrations of certain PCBs in blood are associated with increased risk of NHL.

A cohort study of farming and risk of prostate cancer in Iowa.

Although farming has been linked to prostate cancer mortality, few investigations have addressed its association with prostate cancer incidence. We followed a population-based cohort of 1,177 cancer-free men for up to 9 years and identified 81 incident prostate cancers. Men whose usual occupation was farmer were at an increased risk of prostate cancer after adjustment for age, smoking, alcohol, and dietary factors (RR = 1.7; 95% CI = 1.0-2.7). Exclusion of well-differentiated, localized tumors slightly strengthened the association (RR = 2.0; 95% CI = 1.1-3.6). Risk was confined to older (age 70+ years) farmers (RR = 2.2; 95% CI = 1.1-4.3); we found no evidence of an effect among younger farmers (RR = 1.0; 95% CI = 0.4-2.1).

A case-control study of tobacco use and other non-occupational risk factors for t(14;18) subtypes of non-Hodgkin's lymphoma (United States)

Objective: Non-Hodgkins lymphoma (NHL) encompasses diverse subtypes, and analyzing NHL as a single outcome may mask associations. In a new approach we evaluated associations with subtypes defined by the t(14;18) translocation, reasoning that cases within these subtypes would have more common risk factors than all NHL Combined. Methods: Archival biopsies from cases in a population-based NHL study were assayed for t(14;18) using polymerase chain reaction amplification. Exposures in 68 t(14;18)-positive and 114-negative cases were compared with 1245 controls. The expectation–maximization algorithm was used to fit polytomous regression models based on all available information, including data from 440 unclassified cases. Results: Family history of hemolymphatic cancer was associated with t(14;18)-negative NHL (odds ratio (OR) 2.4, 95% confidence interval (CI) 1.4–3.9), but not t(14;18)-positive NHL. Cigarette smoking was weakly associated with t(14;18)-positive NHL (OR 1.7, CI 0.9–3.3), but ORs decreased as smoking increased. Chewing tobacco was associated with t(14;18)-positive NHL, particularly when used before age 18 (OR 2.5, CI 1.0–6.0, 13 exposed cases). Odds ratios for both case-subtypes were doubled among hair-dye users. Conclusions: Cigarette smoking was not clearly associated with t(14;18)-positive NHL. Family history may be a marker for factors that act specifically through t(14;18)-negative pathogenic mechanisms.

Body mass index, physical activity, and risk of renal cell carcinoma

Objective:To investigate the association between obesity and risk of renal cell carcinoma and to examine whether the association is modified by physical activity.Subjects:A population-based case–control study of 406 patients with renal cell carcinoma and 2434 controls conducted in Iowa.Methods:Information was collected on weight at the ages 20–29, 40–49, and 60–69 years, height, nonoccupational physical activity, diet, and other lifestyle factors. Renal cell carcinoma risk was estimated by odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, total energy intake, and other confounding factors.Results:Height and total energy intake were not associated with risk in either sex. In men, neither physical activity nor level of obesity in any period of life was significantly associated with risk. In women, lower physical activity was associated with higher risk (OR=2.5; 95% CI=1.2–5.2 comparing exercise <1 time/month to >1 time/day). Compared with women in the lowest quartile for BMI, the risks of renal cell carcinoma for women in the highest 10% of BMI in their 20s, 40s, and 60s were 1.4 (CI=0.6–3.1), 1.9 (CI=0.9–4.2), and 2.3 (CI=0.9–6.0), respectively. When analyses were limited to self-respondent data, the corresponding ORs were 2.9 (CI=1.2–7.4), 3.2 (CI=1.3–7.5), and 2.1 (CI=0.7–6.4), respectively. There was little evidence that physical activity modifies the association of BMI with renal cell carcinoma.Conclusion:Nonoccupational physical activity was inversely associated and obesity was positively associated with risk of renal cell carcinoma among women. The risk appeared to be greater for women in the highest 10% of BMI in their 40s. Our finding of little evidence of an interaction between physical activity and BMI requires confirmation.

The driver's license list as a population-based sampling frame in Iowa

Drivers license lists are infrequently used for population-based sampling, presumably because of suspicions of poor population coverage. The 1990 Iowa drivers license list was compared with the 1990 census to evaluate coverage by 5-year age group, sex, resident county, and urbanicity. Coverage exceeded 90% among 15- to 74-year-old men and 15- to 64-year-old women, with uniform coverage by county and county urbanicity group in these age ranges. In Iowa, these lists are convenient and cost-effective and appear to be representative for 25- to 64-year-olds. The representativeness of driver lists in regard to other factors and in other geographic regions deserves further evaluation.

NON-HODGKIN'S LYMPHOMA AMONG ASTHMATICS EXPOSED TO PESTICIDES

We conducted a pooled analysis of population‐based case‐control studies in Iowa, Minnesota and Nebraska to investigate whether asthma modifies risk of non‐Hodgkins lymphoma (NHL) associated with pesticide exposures. Cases (n = 872) diagnosed with NHL from 1980 to 1986 and frequency‐matched controls (n = 2,381) randomly selected from the same geographic areas as the cases were included. Information on use of pesticides and history of asthma was based on interviews. Unconditional logistic regression was used to calculate ORs, adjusted for age, state and vital status. Of all subjects, 177 (45 cases, 132 controls) reported having been told by their doctor that they had asthma. Subjects with an asthma history had a nonsignificantly lower risk of NHL than nonasthmatics (OR = 0.6, 95% CI 0.3–1.4), and there was no main effect of pesticide exposure (OR = 1.0, 95% CI 0.8–1.2). However, asthmatics tended to have larger ORs associated with exposure to pesticides than nonasthmatics. The OR among asthmatics was 1.8 (95% CI 1.1–3.2) for ever‐use of crop insecticides, 2.7 (95% CI 1.0–7.2) for chlordane, 2.4 (95% CI 1.0–5.7) for lindane and 3.7 (95% CI 1.3–10.9) for fonofos. Among nonasthmatics, ORs were 1.1 (0.9–1.3), 1.5 (1.1–2.2), 1.3 (0.97–1.8) and 1.6 (1.0–2.4), respectively. Although there is limited power for assessing interaction, our results suggest that the risk of NHL among asthmatics with pesticide exposure may be higher than among nonasthmatics with pesticide exposure.

Nitrate and nitrite ingestion and risk of ovarian cancer among postmenopausal women in Iowa

Nitrate and nitrite are precursors in the endogenous formation of N‐nitroso compounds (NOC), potential human carcinogens. We evaluated the association of nitrate and nitrite ingestion with postmenopausal ovarian cancer risk in the Iowa Womens Health Study. Among 28,555 postmenopausal women, we identified 315 incident epithelial ovarian cancers from 1986 to 2010. Dietary nitrate and nitrite intakes were assessed at baseline using food frequency questionnaire data. Drinking water source at home was obtained in a 1989 follow‐up survey. Nitrate‐nitrogen (NO3‐N) and total trihalomethane (TTHM) levels for Iowa public water utilities were linked to residences and average levels were computed based on each womans duration at the residence. We computed multivariable‐adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards regression. We tested interactions of nitrate with TTHMs and dietary factors known to influence NOC formation. Ovarian cancer risk was 2.03 times higher (CIu2009=u20091.22–3.38, ptrendu2009=u20090.003) in the highest quartile (≥2.98 mg/L) compared with the lowest quartile (≤0.47 mg/L; reference) of NO3‐N in public water, regardless of TTHM levels. Risk among private well users was also elevated (HRu2009=u20091.53, CIu2009=u20090.93–2.54) compared with the same reference group. Associations were stronger when vitamin C intake was