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Purpose: The purpose of this study was to investigate associations between pesticide exposures and risk of Hodgkin lymphoma (HL) using data from the North American Pooled Project (NAPP)., Methods: Three population-based studies conducted in Kansas, Nebraska, and six Canadian provinces (HL = 507, Controls = 3886) were pooled to estimate odds ratios and 95% confidence intervals for single (never/ever) and multiple (0, 1, 2-4, ≥ 5) pesticides used, duration (years) and, for select pesticides, frequency (days/year) using adjusted logistic regression models. An age-stratified analysis (≤ 40/ > 40 years) was conducted when numbers were sufficient., Results: In an analysis of 26 individual pesticides, ever use of terbufos was significantly associated with HL (OR: 2.53, 95% CI 1.04-6.17). In age-stratified analyses, associations were stronger among those ≤ 40 years of age. No significant associations were noted among those > 40 years old; however, HL cases ≤ 40 were three times more likely to report ever using dimethoate (OR: 3.76 95% CI 1.02-33.84) and almost twice as likely to have ever used malathion (OR: 1.86 95% CI 1.00-3.47). Those ≤ 40 years of age reporting use of 5 + organophosphate insecticides had triple the odds of HL (OR: 3.00 95% CI 1.28-7.03). Longer duration of use of 2,4-D, ≥ 6 vs. 0 years, was associated with elevated odds of HL (OR: 2.59 95% CI 1.34-4.97)., Conclusion: In the NAPP, insecticide use may increase the risk of HL, but results are based on small numbers.

Objective: We re-evaluated reported associations between tobacco use and other factors and non-Hodgkin lymphoma (NHL) t(14; 18)-subtypes based on fluorescence in situ hybridization (FISH) assays believed to be more sensitive than polymerase chain reaction (PCR), previously used for detecting t(14; 18)., Methods: Commercial FISH assays and bcl-2 immunostaining were performed on paraffin sections to determine t(14; 18) and bcl-2 case-subtypes. Polytomous logistic regression models estimated associations between NHL case-subtypes (versus 1,245 population-based controls) and tobacco use as well as other factors., Results: Adjusting for age, state, and proxy status, t(14; 18)-negative NHL was associated with any tobacco use (vs. no tobacco use, OR = 1.9, 95% CI = 1.0-3.5), including current smoking (vs. no cigarette use, OR = 1.9, 95% CI = 1.1-3.2). Tobacco exposures were not clearly associated with t(14; 18)-positive NHL or bcl-2 case-subtypes. Hair-dye use and family history of a hemolymphatic cancer were associated with t(14; 18)-negative NHL, but the number of exposed cases was small., Conclusions: The association between t(14; 18)-negative NHL and cigarette smoking was unexpected given previous evidence of associations between smoking and follicular lymphoma (which is largely t(14; 18)-positive). Future studies characterizing additional molecular characteristics of t(14; 18)-negative NHL may help determine whether the association with smoking may have been causal versus an artifact of chance or bias.

Hormonal factors, possibly related to reproductive characteristics, may play a role in the risk of bladder cancer among women. To study this, we investigated the effects of reproductive factors on female bladder cancer risk. Information on reproductive and other risk factors was gathered in personal interviews from 152 female cases and 166 matched controls from 18 hospitals in five regions of Spain during 1998–2001. Logistic regression was used to estimate the association between bladder cancer and reproductive factors, including ever-parous status, age at first live birth, age at last live birth, age at menarche, age at menopause, menopausal status, and duration of menstruation. After adjustment for age, smoking, and high-risk occupation, ever-parous women were at decreased risk relative to nulliparous women (odds ratio = 0.43, 95% confidence interval = 0.21–0.87). There was no consistent pattern in risk with the age- or duration-related reproductive factors (e.g., age at first live birth, age at last live birth, age at menarche, age at menopause, menopausal status, and duration of menstruation) that we evaluated. Women have a lower risk of bladder cancer than men, and hormonal factors related to childbearing may play a role.

Drinking water and dietary sources of nitrate and nitrite can react in vivo with amines and amides to form N-nitroso compounds (NOC), potent animal carcinogens. Nitrate is a widespread contaminant of drinking water supplies especially in agricultural areas. We conducted a population-based case-control study of renal cell carcinoma in 1986-1989 in Iowa, a state with elevated levels in many public water supplies. We collected a lifetime water source history, but due to limited monitoring data, most analyses focused on the subpopulation, who used Iowa public supplies with nitrate measurements (actual or imputed data) for > or = 70% of their person-years since 1960 (201 cases, 1,244 controls). We computed the average nitrate level and years using a public supply with nitrate levels >5 and >10 mg/l. Dietary nitrate and nitrite were estimated from a 55-item food frequency questionnaire. There was no association of renal cell carcinoma with the average nitrate level and years using public supplies >5 and >10 mg/l nitrate-nitrogen (10+ years >5 mg/l odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.66, 1.60). However, higher nitrate exposure was associated with an increased risk among subgroups with above the median red meat intake (10+ years >5 mg/l OR = 1.91, 95% CI 1.04-3.51) or below the median vitamin C intake (10+ years >5 mg/l OR = 1.90, 95% CI 1.01, 3.56), dietary factors that increase the endogenous formation of NOC. Exclusion of long-term Des Moines residents, a large proportion of the high exposure categories, attenuated the association. These findings deserve additional study in populations with high water nitrate intake and information on dietary intakes.

Objective: A recent study suggested that risk of bladder cancer may be higher in women than in men who smoked comparable amounts of cigarettes. We pooled primary data from 14 case-control studies of bladder cancer from Europe and North America and evaluated differences in risk of smoking by gender., Methods: The pooled analysis included 8316 cases (21% women) and 17,406 controls (28% women) aged 30-79 years. Odds ratios (ORs) and 95% confidence intervals (95% CI) for smoking were adjusted for age and study. Exposure-response was evaluated in a stratified analysis by gender and by generalized additive models., Results: The odds ratios for current smokers compared to nonsmokers were 3.9 (95% CI 3.5-4.3) for males and 3.6 (3.1-4.1) for females. In 11 out of 14 studies, ORs were slightly higher in men. ORs for current smoking were similar for men (OR = 3.4) and women (OR = 3.7) in North America, while in Europe men (OR = 5.3) had higher ORs than women (OR = 3.9). ORs increased with duration and intensity in both genders and the exposure-response patterns were remarkably similar between genders., Conclusion: These results do not support the hypothesis that women have a higher relative risk of smoking-related bladder cancer than men.

Objective: Non-Hodgkin's 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.

Objective: Data from three population-based case-control studies conducted in Kansas, Nebraska, Iowa, and Minnesota were pooled to evaluate the relationship between the use of organophosphate pesticides and non-Hodgkin's lymphoma (NHL) among white male farmers., Methods: The data set included 748 cases of non-Hodgkin's lymphoma and 2236 population-based controls. Telephone or in-person interviews were utilized to obtain information on the use of pesticides. Odds ratios (OR) adjusted for age, state of residence, and respondent status, as well as other pesticide use where appropriate, were estimated by logistic regression., Results: Use of organophosphate pesticides was associated with a statistically significant 50% increased risk of NHL, but direct interviews showed a significantly lower risk (OR = 1.2) than proxy interviews (OR = 3.0). Among direct interviews the risk of small lymphocytic lymphoma increased with diazinon use (OR = 2.8), after adjustment for other pesticide exposures., Conclusions: Although we found associations between the risk of NHL and several groupings and specific organophosphate pesticides, larger risks from proxy respondents complicate interpretation. Associations, however, between reported use of diazinon and NHL, particularly diffuse and small lymphocytic lymphoma, among subjects providing direct interviews are not easily discounted.

Objectives: To update the cancer mortality patterns among Iowa (United States) farmers for the years 1987-93 and compare these results with those previously reported for 1971-86 as well as relate the PMR patterns to risk-factor survey data., Methods: We extracted usual occupation and cause of death from 88,090 Iowa death certificates for White males aged 20 and older for the years 1987-93. Proportional mortality ratios (PMR), adjusted for age, and 95 percent confidence intervals (CI) were calculated using deaths among nonfarmers to generate expected numbers. We compared lifestyle profiles for farmers and nonfarmers using male controls (n = 1,596) from a population-based case-control study conducted in Iowa from 1986-89., Results: Iowa farmers had deficit PMRs for all-cause cancer mortality (PMR = 0.92, CI = 0.90-0.94) and for lung (PMR = 0.70, CI = 0.66-0.73), liver (PMR = 0.65, CI = 0.50-0.86), and other cancer sites strongly related to smoking and alcohol use. Farmers at all ages had excess deaths for cancers of the prostate (PMR = 1.26, CI = 1.19-1.33), rectum (PMR = 1.29, CI = 1.07-1.56), brain (PMR = 1.10, CI = 0.92-1.32), multiple myeloma (PMR = 1.17, CI = 0.98-1.40), non-Hodgkin's lymphoma (PMR = 1.09, CI = 0.96-1.23), and Hodgkin's disease (PMR = 1.62, CI = 1.04-2.54). Younger farmers (aged 20 to 64 years) had excess deaths for colon cancer (PMR = 1.52, CI =1.26-1.85) and skin melanoma (PMR = 1.60, CI = 1.07-2.38), while older farmers (aged 65+ years) had excess deaths for cancers of the pancreas (PMR = 1.18, CI = 1.04-1.34), lip (PMR = 1.58, CI = 0.59-4.21), and leukemia (PMR = 1.26, CI = 1.09-1.46). Since the 1970s, the PMR for stomach cancer has declined to expected values, while the PMRs for prostate, large intestine, pancreas, and Hodgkin's disease have increased; PMRs for other sites are consistent with earlier data. A survey from 1986-89 showed that farmers, compared with nonfarmers, smoked less, used less alcohol, had less formal education, and consumed more total calories, and calories from protein, fat, and meat while consuming fewer calories from fruits and vegetables., Conclusions: Iowa farmers continue to be at elevated risk of mortality due to certain cancers, and, of particular interest, the risk for prostate and colon cancer appears to be increasing since 1970.

A population-based case-control study was conducted in Washington County, Maryland (United States) to explore the association between incident bladder cancer and exposure to drinking water from chlorinated surface sources. Cancer cases were White residents, enumerated in a 1975 county census and reported to the Washington County Cancer Registry (n = 294) between 1975 and 1992. White controls, frequency matched by age (+/- 5 years) and gender, were selected randomly from the census (n = 2,326). Households receiving municipal water, which generally derived from chlorinated surface waters, were treated as having 'high exposure' and all others, as 'low exposure.' Duration of exposure to type of drinking water was based on length of residence in the census household prior to 1975. Odds ratios (OR) were calculated using logistic regression methods, adjusting for age, gender, tobacco use, and urbanicity. Bladder cancer risk was associated weakly in the general population with duration of exposure to municipal water. The association was limited to those who had smoked cigarettes. In ever-smokers compared with never-smokers with low exposure, the adjusted ORs for bladder cancer risk with increasing exposure were 1.3, 1.4, 1.4, 1.7, 2.2, 2.8, respectively, for 0, 1-10, 11-20, 21-30, 31-40, > 40 years' exposure duration. The ORs in smokers were not diminished after adjusting for smoking history and intensity.

Epidemiologic evidence on the relation between contaminants in drinking water and cancer is reviewed. The reviewed studies cover exposure to: disinfection byproducts; nitrate; arsenic and other metals; volatiles and contaminants from hazardous waste sites; asbestiform fibers; radionuclides; and fluoride. Most investigations are ecologic, with some confirmation of elevated risk from individual-based studies. In the case of waterborne arsenic, and possibly chlorination byproducts, there is a consistent but small body of epidemiologic evidence of an association with one or more types of cancer. Nitrate in groundwater has increased greatly over the years, and the demonstration of endogenous nitrosation among highly exposed subjects raises concern of elevated cancer risk. However, the epidemiologic data are not yet sufficient to draw a conclusion. There is a diversity of studies among populations exposed to water contaminated with pesticides, volatile organics, or mixtures from hazardous waste sites. Studies of asbestiform fibers and radionuclides in water are not conclusive, but there are suggested elevations of several cancer sites in highly exposed populations. There is no suggestion that fluoride in drinking water is linked with elevated risk of cancer. As topics for epidemiologic evaluation, drinking water contaminants pose methodologic problems common to studies designed to detect relatively small elevations in risk, with the added challenge of assessing exposures for many years in the past. Nevertheless, epidemiologic assessment is valuable and clearly warranted, given the potential public health impact of small risk elevations among very large exposed populations, and the limitations of toxicologic experiments in assessing carcinogenic risk of complex mixtures or of compounds for which appropriate animal models are not available.

The role of tobacco in the etiology of non-Hodgkin's lymphoma (NHL) was evaluated in a combined analysis of data from three population-based case-control studies conducted in four midwestern states of the United States: Nebraska, Iowa, Minnesota, and Kansas. Interviews were obtained from 1,177 cases (993 men, 184 women) and 3,625 controls (2,918 men, 707 women) or, if deceased, from their next-of-kin. Overall, there was no association between NHL and tobacco use (odds ratio [OR] = 1.0, 95 percent confidence interval [CI] = 0.8-1.1) or cigarette smoking (OR = 1.0, CI = 0.8-1.1). A slight negative association evident in analyses by intensity and duration of smoking was not present when interviews from proxy respondents were eliminated. There was a suggestion of a positive association between smoking and NHL among women (OR = 1.3, CI = 0.9-1.9), although there was no clear exposure-response relationship. This large case-control analysis provides no evidence that smoking is linked to the development of NHL among men. The possible role of smoking in the etiology of NHL among women needs further evaluation.

Little is known about dietary factors and non-Hodgkin's 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 nonsignificantly 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 differences in the associations of nutrient intakes 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.

The influence of parity on the risk of cancers of the female breast and reproductive organs is well established. However, non-reproductive sites have received less attention. Mail questionnaire data gathered from incident female cases (169 brain; 332 colon; 260 rectal; 145 kidney; and 169 pancreas cancers), and 821 population-based controls in Iowa (United States) were used to measure the effect of parity and age at first birth on risk of these malignancies. Relative to nulliparous women, ever-parous women were at significantly decreased risk of brain cancer (odds ratio [OR] = 0.44, 95 percent confidence interval [CI] = 0.3-0.7) and of colon cancer (OR = 0.67, CI = 0.5-0.97), after adjustment for age and other risk factors. The OR for the other sites did not differ significantly from 1.0. The lower risk of brain cancer among parous women was similar in younger and older age groups, in patients diagnosed with glioblastoma and astrocytoma, and among ever- and never-smokers. The findings for colon cancer are consistent with observations from other studies. In the context of limited laboratory and clinical evidence implicating hormones in brain neoplasia, these findings may suggest a role for hormonal factors in brain cancer etiology. Hormonal factors deserve more detailed future consideration as risk factors in brain cancer.

The excess of bladder cancer in males (M:F ratio of 4:1 in the United States) is not explained fully by gender differences in smoking habits or occupational exposures. Laboratory studies suggest that some androgenic hormones stimulate (or do not inhibit) oncogenesis in bladder tissue, and that estrogenic hormones have the opposite effect. These observations suggest that bladder cancer risk in females may be modified by sex hormones which undergo profound changes during and following pregnancy. Mail-questionnaire data from 317 incident female cases, and 833 population-based controls in Iowa were used to measure the effect of parity and maternal age at first birth on bladder cancer risk. Parous women were at decreased risk relative to nulliparous women (odds ratio [OR] = 0.67, 95 percent confidence interval [CI] = 0.44-1.00), after adjustment for age, tobacco use, and previous bladder infection. The overall risk reduction was restricted to women who had never smoked (OR = 0.51, CI = 0.30-0.88), with no apparent effect of parity among ever-smokers (OR = 0.93, CI = 0.49-1.77). Risk appeared to decrease with increasing age at first birth, but did not vary with increasing parity after the first birth. Our findings are consistent with the hypothesis that oncogenesis in transitional cell tissue of the human bladder is influenced by sex hormones, and that hormonal changes related to pregnancy thereby can decrease risk.