Exploring spatial-temporal patterns of disease incidence and mortality can identify areas of significantly elevated or decreased risk, providing potential etiologic clues. Several methodological issues arise in spatial-temporal analysis of cancer, including population mobility, disease latency, and confounding, but applying modern statistical methods to case-control studies with residential histories can address these issues. As an example, we present a spatial-temporal analysis of non-Hodgkin lymphoma (NHL) risk using data from Los Angeles County, one of four centers in a population-based case-control study. Using residential histories, we fitted generalized additive models (GAMs) adjusted for known risk factors to model spatially the probability that an individual had NHL and identify areas of significantly elevated NHL risk. In previous analyses using models with single lag times, the lag time of 20 years yielded the most significant decrease in model deviance. To better assess cumulative effects of unmeasured environmental exposures over space and time, we considered models that allowed for multiple residences per subject through spatial smoothing functions of residential location at different times. We found that the model with the best goodness-of-fit included components for residential change and residential duration, although the model that included residential duration was not meaningfully better than the model that included only residential change. The estimated cumulative spatial risk surface from the model with residential change amplified the risk surface in some areas compared with the surface based on the model with a single component for the most significant time lag.
cancer; generalized additive model; spatial risk; latency; exposure
The purpose of this study is to evaluate cancer risk associated with raising animals as commodities, which is associated with a variety of exposures, such as infectious agents and endotoxins.
Information was available for 49,884 male farmers in the Agricultural Health Study, who reported livestock and poultry production at enrollment (1993–1997). Cancer incidence data were obtained through annual linkage to state registries. Using Poisson regression analyses, we evaluated whether the number and type of animals raised on the farm impacted cancer risk.
Overall, 31,848 (63.8%) male farmers reported raising any animals. Lung cancer risk decreased with increasing number of livestock on the farm (p-trend=0.04) and with raising poultry (Relative Risk (RR)= 0.6; 95% Confidence Interval (CI): 0.4–0.97). Raising poultry was associated with an increased risk of colon cancer (RR=1.4; 95% CI: 0.99–2.0) with further increased with larger flocks (p-trend=0.02). Risk of non-Hodgkin lymphoma was also elevated in those who raised poultry (RR=1.6; 95% CI: 1.0–2.4), but there was no evidence of increased risk with larger flocks (p-trend=0.5). Raising sheep was associated with a significantly increased risk of multiple myeloma (RR=4.9; 95% CI: 2.4–12.0). Performing veterinary services increased the risk of Hodgkin lymphoma (RR=12.2; 95% CI: 1.6–96.3).
We observed an inverse association between raising poultry and livestock and lung cancer risk and some evidence of increased risk of specific lymphohematopoietic malignancies with specific types of animals and performing veterinary services. Further research into associations between raising animals and cancer risk should focus on identification of etiologic agents.
livestock; poultry; cancer; cohort study; agriculture
Background: Residential pesticide exposure has been linked to adverse health outcomes in adults and children. High-quality exposure estimates are critical for confirming these associations. Past epidemiologic studies have used one measurement of pesticide concentrations in carpet dust to characterize an individual’s average long-term exposure. If concentrations vary over time, this approach could substantially misclassify exposure and attenuate risk estimates.
Objectives: We assessed the repeatability of pesticide concentrations in carpet dust samples and the potential attenuation bias in epidemiologic studies relying on one sample.
Methods: We collected repeated carpet dust samples (median = 3; range, 1–7) from 21 homes in Fresno County, California, during 2003–2005. Dust was analyzed for 13 pesticides using gas chromatography–mass spectrometry. We used mixed-effects models to estimate between- and within-home variance. For each pesticide, we computed intraclass correlation coefficients (ICCs) and the estimated attenuation of regression coefficients in a hypothetical case–control study collecting a single dust sample.
Results: The median ICC was 0.73 (range, 0.37–0.95), demonstrating higher between-home than within-home variability for most pesticides. The expected magnitude of attenuation bias associated with using a single dust sample was estimated to be ≤ 30% for 7 of the 13 compounds evaluated.
Conclusions: For several pesticides studied, use of one dust sample to represent an exposure period of approximately 2 years would not be expected to substantially attenuate odds ratios. Further study is needed to determine if our findings hold for longer exposure periods and for other pesticides.
dust; environmental exposure; pesticides; reliability
Nitrate and nitrite are precursors in the formation of N-nitroso compounds. We recently found a 40% increased risk of NHL with higher dietary nitrite intake and significant increases in risk for follicular and T-cell lymphoma. It is possible that these compounds also affect NHL prognosis by enhancing cancer progression in addition to development by further impairing immune system function. To test the hypothesis that nitrate and nitrite intake affects NHL survival, we evaluated the association in study participants that have been followed post-disease diagnosis in a population-based case-control study among women in Connecticut. We did not observe a significant increasing trend of mortality for NHL overall or by subtype for nitrate or nitrite intake for deaths from NHL or death from any cause, although a borderline significant protective trend was observed for follicular lymphoma with increasing nitrate intake. We did not identify a difference in overall survival for nitrate (P = 0.39) or for nitrite (P = 0.66) or for NHL specific survival for nitrate (P = 0.96) or nitrite (P = 0.17). Thus, our null findings do not confer support for the possibility that dietary nitrate and nitrite intake impacts NHL survival by promoting immune unresponsiveness.
Iron can cause oxidative stress and DNA damage, and heme iron can catalyze endogenous formation of N-nitroso compounds, which are potent carcinogens. Dietary iron promotes esophageal cancer incidence in animal studies and has been identified as a growth factor for Helicobacter pylori, an established risk factor for stomach cancer.
We conducted a population-based case-control study of adenocarcinoma of the esophagus (n=124) and stomach (n=154) and 449 controls in Nebraska. Heme iron and total iron intake were estimated from a food-frequency questionnaire and databases of heme and total iron. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) adjusted for known risk factors.
Esophageal cancer was positively associated with higher intakes of heme iron (ORQ4 vs. Q1 =3.04, 95% CI 1.20–7.72; p-trend=0.009) and total iron from meat sources (ORQ4 vs. Q1 =2.67, 95% CI 0.99–7.16; p-trend=0.050). Risk of stomach cancer was elevated among those with higher intakes of heme iron (ORQ4vs.Q1=1.99, 95% CI 1.00–3.95, p-trend=0.17) and total iron from meat (OR=2.26, 95% CI 1.14–4.46; p-trend=0.11). Iron intake from all dietary sources was not significantly associated with risk of either cancer.
Our results suggest that high intakes of heme and iron from meat may be important dietary risk factors for esophageal and stomach cancer and may partly explain associations with red meat.
Iron; heme iron; nutrition; esophageal cancer; stomach cancer
Background: Home and garden pesticide use has been linked to cancer and other health outcomes in numerous epidemiological studies. Exposure has generally been self-reported, so the assessment is potentially limited by recall bias and lack of information on specific chemicals.
Objectives: As part of an integrated assessment of residential pesticide exposure, we identified active ingredients and described patterns of storage and use.
Methods: During a home interview of 500 residentially stable households enrolled in the Northern California Childhood Leukemia Study during 2001–2006, trained interviewers inventoried residential pesticide products and queried participants about their storage and use. U.S. Environmental Protection Agency registration numbers, recorded from pesticide product labels, and pesticide chemical codes were matched to public databases to obtain information on active ingredients and chemical class. Poisson regression was used to identify independent predictors of pesticide storage. Analyses were restricted to 259 participating control households.
Results: Ninety-five percent (246 of 259) of the control households stored at least one pesticide product (median, 4). Indicators of higher sociodemographic status predicted more products in storage. We identified the most common characteristics: storage areas (garage, 40%; kitchen, 20%), pests treated (ants, 33%; weeds, 20%), pesticide types (insecticides, 46%; herbicides, 24%), chemical classes (pyrethroids, 77%; botanicals, 50%), active ingredients (pyrethrins, 43%) and synergists (piperonyl butoxide, 42%). Products could contain multiple active ingredients.
Conclusions: Our data on specific active ingredients and patterns of storage and use will inform future etiologic analyses of residential pesticide exposures from self-reported data, particularly among households with young children.
exposure assessment; pesticides; population-based study; residential pesticide use; U.S. EPA
Ovarian cancer is a leading cause of cancer death among women in the United States and it has the highest mortality rate of all gynecologic cancers. Internationally, there is a five-fold variation in incidence and mortality of ovarian cancer, which suggests a role for environmental factors, including diet. Nitrate and nitrite are found in various food items and they are precursors of N-nitroso compounds, which are known carcinogens in animal models. We evaluated dietary nitrate and nitrite intake and epithelial ovarian cancer in the National Institutes of Health (NIH)-AARP Diet and Health Study, including 151 316 women aged 50–71 years at the time of the baseline questionnaire in 1995–1996. The nitrate and nitrite intake was assessed using a 124-item validated food frequency questionnaire. Through 31 December 2006, 709 incident epithelial ovarian cancer cases with complete dietary information were identified. Using Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs), women in the highest intake quintile of dietary nitrate had a 31% increased risk (95% CI: 1.01–1.68) of epithelial ovarian cancer, compared with those in the lowest intake quintile. Although there was no association for total dietary nitrite, those in the highest intake category of animal sources of nitrite had a 34% increased risk (95% CI: 1.05–1.69) of ovarian cancer. There were no clear differences in risk by histologic subtype of ovarian cancer. Our findings suggest that a role of dietary nitrate and nitrite in ovarian cancer risk should be followed in other large cohort studies.
epithelial; nitrate and nitrite; ovarian cancer
Background Previous studies suggest an association between obesity and oesophageal (OA) and oesophagogastric junction adenocarcinomas (OGJA). However, these studies have been limited in their ability to assess whether the effects of obesity vary by gender or by the presence of gastro-oesophageal reflux (GERD) symptoms.
Methods Individual participant data from 12 epidemiological studies (8 North American, 3 European and 1 Australian) comprising 1997 OA cases, 1900 OGJA cases and 11 159 control subjects were pooled. Logistic regression was used to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between body mass index (BMI, kg/m2) and the risk of OA and OGJA. Random-effects meta-analysis was used to combine these ORs. We also investigated effect modification and synergistic interaction of BMI with GERD symptoms and gender.
Results The association of OA and OGJA increased directly with increasing BMI (P for trend <0.001). Compared with individuals with a BMI <25, BMI ≥40 was associated with both OA (OR 4.76, 95% CI 2.96–7.66) and OGJA (OR 3.07, 95% CI 1.89–4.99). These associations were similar when stratified by gender and GERD symptoms. There was evidence for synergistic interaction between BMI and GERD symptoms in relation to OA/OGJA risk.
Conclusions These data indicate that BMI is directly associated with OA and OGJA risk in both men and women and in those with and without GERD symptoms. Disentangling the relationship between BMI and GERD will be important for understanding preventive efforts for OA and OGJA.
Oesophageal neoplasms; aetiology; risk factors; gastro-oesophageal reflux; obesity; oesophagogastric junction
Although impaired lung function in general has been associated with an increased risk of lung cancer, past studies typically have not attempted to investigate separately the obstructive and restrictive components of respiratory impairment. To deal with this question further, data from a large (n = 176 997) cohort of male Swedish construction workers, for whom spirometry measurements before follow‐up were available, were analysed.
Cancer incidence for 1971–2001 was obtained through linkage with the national cancer registry. Using a modification of the Global Initiative for Chronic Obstructive Lung Disease criteria for chronic obstructive pulmonary disease (COPD), subjects were classified into five categories of lung function: normal, mild COPD, moderate COPD, severe COPD and restrictive lung disease (RLD). Rate ratios (RR) and 95% confidence intervals (CI) for lung cancer across lung function categories were calculated using Poisson regression, adjusted for age and smoking. Other end points (histological types of lung cancer, non‐lung tobacco‐related cancers, other cancers, total mortality) were also investigated.
834 incident cases of lung cancer were identified. Increased rates of lung cancer were observed for both COPD (mild: RR 1.5, 95% CI 1.2 to 1.9; moderate/severe: RR 2.2, 95% CI 1.8 to 2.7) and RLD (RR 2.0, 95% CI 1.6 to 2.5) relative to normal lung function. These associations did not meaningfully change on applying follow‐up lag times of 5, 10 and 15 years after spirometry. When analysed by histological type, associations with both COPD and RLD were stronger for squamous cell carcinoma and small cell carcinoma, and weaker for adenocarcinoma. Both COPD and RLD were associated with increased rates of total mortality.
Obstructive and restrictive impairments in lung function are associated with increased lung cancer risk.
We conducted a population-based case-control study of adenocarcinoma of the stomach and esophagus in Nebraska, U.S.A. Nitrate concentrations in public drinking water supplies were linked to residential water source histories. Among those using private wells at the time of the interview, we measured nitrate levels in water samples from wells. Dietary nitrate and nitrite were estimated from a food-frequency questionnaire. Among those who primarily used public water supplies (79 distal stomach, 84 esophagus, 321 controls), average nitrate levels were not associated with risk (highest versus lowest quartile: stomach OR=1.2, 95% CI [0.5–2.7]; esophagus OR=1.3, 95% CI [0.6–3.1]). We observed the highest ORs for distal stomach cancer among those with higher water nitrate ingestion and higher intake of processed meat compared with low intakes of both; however, the test for positive interaction was not significant (p=0.213). We did not observe this pattern for esophagus cancer. Increasing intake of nitrate and nitrite from animal sources was associated with elevated ORs for stomach cancer and with a significant positive trend in risk of esophagus cancer (P-trend=0.325 and 0.015, respectively). Larger studies with higher exposures to drinking water sources of nitrate are warranted to further evaluate N-nitroso compound precursors as risk factors for these cancers.
Nitrate; nitrite; stomach cancer; esophagus cancer; diet; drinking water
Background and aims
Alcohol intake is a strong and well-established risk factor for esophageal squamous cell carcinoma (ESCC), but the association with esophageal adenocarcinoma (EA) or adjacent tumors of the esophagogastric junction (EGJA), remains unclear. Therefore, we determined the association of alcohol intake with ESCC, EA, and EGJA in nine case-control studies and two cohort studies of the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium (BEACON).
Materials and methods
We collected information on alcohol intake, age, sex, education, body mass index, gastroesophageal reflux, and tobacco smoking from each study. Along with 10,854 controls, 1,821 EA, and 1,837 EGJA, seven studies also collected ESCC cases (n=1,016). Study-specific odds ratios (OR) and 95% confidence intervals (CI) were calculated from multivariate-adjusted logistic regression models for alcohol intake in categories compared to non-drinkers. Summary risk estimates were obtained by random effects models.
We observed no increase in risk of EA or EGJA for increasing levels of any of the alcohol intake measures examined. ORs for the highest frequency category (≥7 drinks per day) were 0.97 (95% CI = 0.68-1.36) for EA and 0.77 (95% CI = 0.54-1.10) for EGJA. Suggestive findings linked moderate intake (e.g. 0.5 to <1 drinks per day) to decreased risk of EA (OR = 0.63 95% CI = 0.41-0.99) and EGJA (OR = 0.78; 95% CI = 0.62-0.99). In contrast, alcohol intake was strongly associated with increased risk of ESCC (OR for ≥7 drinks per day= 9.62, 95%CI=4.26-21.71).
In contrast to ESCC, higher alcohol consumption was not associated with increased risk of either EA or EGJA. The apparent inverse association observed with moderate alcohol intake should be evaluated in future prospective studies.
Alcohol Drinking; Esophageal Neoplasms; Stomach Neoplasms; Epidemiology
We hypothesized that diabetes may play a role in thyroid cancer risk due to the parallel secular rise in diabetes prevalence and morbidity in the United States, the higher prevalence of thyroid disorders among diabetics compared with the general population, and the potential roles of metabolic syndrome, obesity, and diabetes as precipitating factors in cancer development.
We assessed the association between self-reported diabetes and the risk of differentiated thyroid cancer in the NIH-AARP Diet and Health Study, a prospective cohort of 200,556 women and 295,992 men, 50–71 years of age, in 1995–1996. Diabetes status and information on potential confounders was ascertained using a self-administered questionnaire. During an average of 10 years of follow-up, 585 thyroid cancer cases were identified. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer and thyroid cancer subtypes in men and women according to diabetes status.
Nine percent of the total baseline cohort reported a history of diabetes (7% of women, 10% of men). A nonsignificant 25% increase in thyroid cancer risk (HR = 1.25; 95% CI: 0.95–1.64) was associated with diabetes. Among women, the risk was significantly increased (HR = 1.46, 95% CI: 1.01–2.10). The risk was not elevated among men (HR = 1.04, 95% CI: 0.69–1.58). In this cohort, diabetic women with differentiated thyroid cancer were at somewhat higher risk of follicular thyroid cancer (HR = 1.92; 95% CI: 0.86–4.27) than papillary thyroid cancer (HR = 1.25; 95% CI: 0.80–1.97).
This study lends support to the hypothesis that diabetes increases the risk of differentiated thyroid cancer.
Nitrate and nitrite are precursors of N-nitroso compounds, which induce tumors of the pancreas in animals. The authors evaluated the relation of dietary nitrate and nitrite to pancreatic cancer risk in the NIH-AARP Diet and Health Study. Nitrate and nitrite intakes were assessed at baseline using a 124-item food frequency questionnaire. During approximately 10 years of follow-up between 1995 and 2006, 1,728 incident pancreatic cancer cases were identified. There was no association between total nitrate or nitrite intake and pancreatic cancer in men or women. However, men in the highest quintile of summed nitrate/nitrite intake from processed meat had a nonsignificantly elevated risk of pancreatic cancer (hazard ratio = 1.18, 95% confidence interval: 0.95, 1.47; P-trend = 0.11). The authors observed a stronger increase in risk among men for nitrate/nitrite intake from processed meat at ages 12–13 years (highest quintile vs. lowest: hazard ratio = 1.32, 95% confidence interval: 0.99, 1.76; P-trend = 0.11), though the relation did not achieve statistical significance. The authors found no associations between adult or adolescent nitrate or nitrite intake from processed meats and pancreatic cancer among women. These results provide modest evidence that processed meat sources of dietary nitrate and nitrite may be associated with pancreatic cancer among men and provide no support for the hypothesis in women.
diet; nitrates; nitrites; nitroso compounds; pancreatic neoplasms
Ingested nitrate can be endogenously reduced to nitrite, which may form N-nitroso compounds, known potent carcinogens. However, some studies have reported no or inverse associations between dietary nitrate intake and cancer risk. These associations may be confounded by a protective effect of folate, which plays a vital role in DNA repair. We evaluated the interaction of dietary and water nitrate intake with total folate intake on breast cancer risk in the Iowa Women’s Health Study. Dietary intake was assessed at study baseline. Nitrate intake from public water was assessed using a historical database on Iowa municipal water supplies. After baseline exclusions, 34,388 postmenopausal women and 2,875 incident breast cancers were included. Overall, neither dietary nor water nitrate was associated with breast cancer risk. Among those with folate intake ≥400 μg/d, breast cancer risk was significantly increased in public water users with the highest nitrate quintile (HR=1.40, 95%CI=1.05–1.87) and private well users (HR=1.38, 95%CI=1.05–1.82) compared to public water users with the lowest nitrate quintile; in contrast, there was no association among those with lower folate intake. Our findings do not support a previous report of increased risk of breast cancer among individuals with high dietary nitrate but low folate intake.
nitrate; folate; interaction; breast cancer; epidemiological
During the past several decades, an increasing incidence of thyroid cancer has been observed worldwide. Nitrate inhibits iodide uptake by the thyroid, potentially disrupting thyroid function. An increased risk of thyroid cancer associated with nitrate intake was recently reported in a cohort study of older women in Iowa. We evaluated dietary nitrate and nitrite intake and thyroid cancer risk overall and for subtypes in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, a large prospective cohort of 490,194 men and women, ages 50–71 years in 1995–1996. Dietary intakes were assessed using a 124-item food frequency questionnaire. During an average of 7 years of follow-up we identified 370 incident thyroid cancer cases (170 men, 200 women) with complete dietary information. Among men, increasing nitrate intake was positively associated with thyroid cancer risk (relative risk (RR) for the highest quintile versus lowest quintile RR=2.28, 95% CI: 1.29–4.04l; p-trend <0.001); however, we observed no trend with intake among women (p-trend=0.61). Nitrite intake was not associated with risk of thyroid cancer for either men or women. We evaluated risk for the two main types of thyroid cancer. We found positive associations for nitrate intake and both papillary (RR = 2.10; 95%CI: 1.09–4.05; p-trend=0.05) and follicular thyroid cancer (RR= 3.42; 95%CI: 1.03–11.4; p-trend=0.01) among men. Nitrite intake was associated with increased risk of follicular thyroid cancer (RR= 2.74; 95%CI: 0.86–8.77; p-trend=0.04) among men. Our results support a role of nitrate in thyroid cancer risk and suggest that further studies to investigate these exposures are warranted.
There is increasing interest in using chemicals measured in carpet dust as indicators of chemical exposures. However, investigators have rarely sampled dust repeatedly from the same households and therefore little is known about the variability of chemical levels that exist within and between households in dust samples.
We analyzed 9 polycyclic aromatic hydrocarbons, 6 polychlorinated biphenyls, and nicotine in 68 carpet-dust samples from 21 households in agricultural communities of Fresno County, California collected from 2003-2005. Chemical concentrations (ng per g dust) ranged from < 2-3,609 for 9 polycyclic aromatic hydrocarbons, from < 1-150 for 6 polychlorinated biphenyls, and from < 20-7,776 for nicotine. We used random-effects models to estimate variance components for concentrations of each of these carpet-dust chemicals and calculated the variance ratio, λ, defined as the ratio of the within-household variance component to the between-household variance component. Subsequently, we used the variance ratios calculated from our data, to illustrate the potential effect of measurement error on the attenuation of odds ratios in hypothetical case-control studies. We found that the median value of the estimated variance ratios was 0.33 (range: 0.13-0.72). Correspondingly, in case-control studies of associations between these carpet-dust chemicals and disease, given the collection of only one measurement per household and a hypothetical odds ratio of 1.5, we expect that the observed odds ratios would range from 1.27 to 1.43. Moreover, for each of the chemicals analyzed, the collection of three repeated dust samples would limit the expected magnitude of odds ratio attenuation to less than 20%.
Our findings suggest that attenuation bias should be relatively modest when using these semi-volatile carpet-dust chemicals as exposure surrogates in epidemiologic studies.
Red and processed meats could increase cancer risk via several potential mechanisms involving iron, heterocyclic amines, polycyclic aromatic hydrocarbons and N-nitroso compounds. Although there have been multiple studies of meat and colorectal cancer, other gastrointestinal malignancies are understudied.
We estimated hazards ratios (HR) and 95% confidence intervals (CI) for the association between meat, meat components, and meat cooking by-products and risk of esophageal or gastric cancer in a large cohort study. During approximately 10 years of follow-up, we accrued 215 esophageal squamous cell carcinomas, 630 esophageal adenocarcinomas, 454 gastric cardia adenocarcinomas and 501 gastric non-cardia adenocarcinomas.
Red meat intake was positively associated with esophageal squamous cell carcinoma (HR for the top versus bottom quintile = 1.79, 95% CI: 1.07–3.01, P for trend = 0.019). Individuals in the highest intake quintile of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) had an increased risk for gastric cardia cancer (HR = 1.44, 95% CI: 1.01–2.07, P for trend = 0.104). Furthermore, those in the highest quintile of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) or heme iron intake had a suggestive increased risk for esophageal adenocarcinoma (HR = 1.35, 95% CI: 0.97–1.89, P for trend = 0.022; HR = 1.45, 95% CI: 0.99–2.12, P for trend = 0.463; HR = 1.47, 95% CI: 0.99-2.20, P for trend = 0.063, respectively). Benzo[a]pyrene, nitrate and nitrite were not associated with esophageal or gastric cancer.
We found positive associations between red meat intake and esophageal squamous cell carcinoma, and between DiMeIQx intake and gastric cardia cancer.
meat; heterocyclic amines; iron; nitrate; nitrite; esophageal cancer; gastric cancer
The increasing incidence of thyroid cancer in the United States is well documented. In this study, we assessed the incidence patterns by histologic type according to demographic and tumor characteristics to further our understanding of these cancers.
We used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program for cases diagnosed during 1992–2006 to investigate patterns for the four major histologic types of thyroid cancer by gender, race/ethnicity, and age as well as registry, tumor stage, and size.
Among women, papillary thyroid cancer rates were highest among Asians (10.96 per 100,000 woman-years) and lowest among blacks (4.90 per 100,000 woman-years); follicular cancer rates did not vary substantially by race/ethnicity (p-values >0.05), medullary cancer rates were highest among Hispanics (0.21 per 100,000 woman-years) and whites (0.22 per 100,000 woman-years), and anaplastic rates were highest among Hispanics (0.17 per 100,000 woman-years). Among men, both papillary and follicular thyroid cancer rates were highest among whites (3.58 and 0.58 per 100,000 man-years, respectively), medullary cancer rates were highest among Hispanics (0.18 per 100,000 man-years), and anaplastic rates were highest among Asians (0.11 per 100,000 man-years). Racial/ethnic-specific rates did not vary notably across registries. In contrast to age-specific rates of papillary thyroid cancer that peaked in midlife (age 50), especially pronounced among women, rates for follicular, medullary, and anaplastic types continued to rise across virtually the entire age range, especially for anaplastic carcinomas. Female-to-male incidence rate ratios among whites decreased with age most steeply for the follicular type and least steeply for the medullary type; it was <1 until the very oldest ages for the anaplastic type.
We conclude that the similar age-specific patterns and lack of geographical variation across the SEER racial/ethnic groups indicate that detection effects cannot completely explain the observed thyroid cancer incidence patterns as variation in the amount or quality of healthcare provided has been shown to vary by SEER racial/ethnic groups, gender, and age. We find that the variations in age-specific patterns by gender and across histologic types are intriguing and recommend that future etiologic investigation focus on exogenous and endogenous exposures that are experienced similarly by racial/ethnic groups, more strongly among women, and distinctively by age.
Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat-related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons. We comprehensively investigated the association between meat and meat components and bladder cancer.
During 7 years of follow-up, 854 transitional cell bladder cancer cases were identified among 300,933 men and women who completed a validated food frequency questionnaire in the large prospective NIH-AARP Diet and Health Study. We estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat using quantitative databases of measured values. We calculated total dietary nitrate and nitrite based on literature values.
The hazard ratios (HR) and 95% confidence intervals (CI) for red meat (HR for fifth compared to first quintile=1.22, 95% CI=0.96–1.54, p-trend=0.07) and the HCA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (HR=1.19, 95% CI=0.95–1.48, p-trend=0.06) conferred a borderline statistically significant increased risk of bladder cancer. We observed positive associations in the top quintile for total dietary nitrite (HR=1.28, 95% CI=1.02–1.61, p-trend= 0.06) and nitrate plus nitrite intake from processed meat (HR=1.29 95% CI=1.00–1.67, p-trend= 0.11).
These findings provide modest support for a role for total dietary nitrite and nitrate plus nitrite from processed meat in bladder cancer. Our results also suggest a positive association between red meat and PhIP and bladder carcinogenesis.
Diet; bladder cancer; meat; nitrate; nitrite
Previous studies that showed an association between smoking and adenocarcinomas of the esophagus and esophagogastric junction were limited in their ability to assess differences by tumor site, sex, dose–response, and duration of cigarette smoking cessation.
We used primary data from 10 population-based case–control studies and two cohort studies from the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium. Analyses were restricted to white non-Hispanic men and women. Patients were classified as having esophageal adenocarcinoma (n = 1540), esophagogastric junctional adenocarcinoma (n = 1450), or a combination of both (all adenocarcinoma; n = 2990). Control subjects (n = 9453) were population based. Associations between pack-years of cigarette smoking and risks of adenocarcinomas were assessed, as well as their potential modification by sex and duration of smoking cessation. Study-specific odds ratios (ORs) estimated using multivariable logistic regression models, adjusted for age, sex, body mass index, education, and gastroesophageal reflux, were pooled using a meta-analytic methodology to generate summary odds ratios. All statistical tests were two-sided.
The summary odds ratios demonstrated strong associations between cigarette smoking and esophageal adenocarcinoma (OR = 1.96, 95% confidence interval [CI] = 1.64 to 2.34), esophagogastric junctional adenocarcinoma (OR = 2.18, 95% CI = 1.84 to 2.58), and all adenocarcinoma (OR = 2.08, 95% CI = 1.83 to 2.37). In addition, there was a strong dose–response association between pack-years of cigarette smoking and each outcome (P < .001). Compared with current smokers, longer smoking cessation was associated with a decreased risk of all adenocarcinoma after adjusting for pack-years (<10 years of smoking cessation: OR = 0.82, 95% CI = 0.60 to 1.13; and ≥10 years of smoking cessation: OR = 0.71, 95% CI = 0.56 to 0.89). Sex-specific summary odds ratios were similar.
Cigarette smoking is associated with increased risks of adenocarcinomas of the esophagus and esophagogastric junction in white men and women; compared with current smoking, smoking cessation was associated with reduced risks.
Background: Ingestion of inorganic arsenic in drinking water is recognized as a cause of bladder cancer when levels are relatively high (≥ 150 µg/L). The epidemiologic evidence is less clear at the low-to-moderate concentrations typically observed in the United States. Accurate retrospective exposure assessment over a long time period is a major challenge in conducting epidemiologic studies of environmental factors and diseases with long latency, such as cancer.
Objective: We estimated arsenic concentrations in the water supplies of 2,611 participants in a population-based case–control study in northern New England.
Methods: Estimates covered the lifetimes of most study participants and were based on a combination of arsenic measurements at the homes of the participants and statistical modeling of arsenic concentrations in the water supply of both past and current homes. We assigned a residential water supply arsenic concentration for 165,138 (95%) of the total 173,361 lifetime exposure years (EYs) and a workplace water supply arsenic level for 85,195 EYs (86% of reported occupational years).
Results: Three methods accounted for 93% of the residential estimates of arsenic concentration: direct measurement of water samples (27%; median, 0.3 µg/L; range, 0.1–11.5), statistical models of water utility measurement data (49%; median, 0.4 µg/L; range, 0.3–3.3), and statistical models of arsenic concentrations in wells using aquifers in New England (17%; median, 1.6 µg/L; range, 0.6–22.4).
Conclusions: We used a different validation procedure for each of the three methods, and found our estimated levels to be comparable with available measured concentrations. This methodology allowed us to calculate potential drinking water exposure over long periods.
arsenic; environmental epidemiology; exposure assessment; geographic information systems; water quality modeling; water supply
N-nitroso compounds (NOCs) are found in processed meat and are formed endogenously from intake of nitrite and nitrate. Endogenous NOC formation is antagonized by nitrosation inhibitors in fruit and vegetables (e.g., vitamin C) and promoted by heme in red meat. It has been hypothesized that a diet resulting in high exposure to NOCs increases adult glioma risk.
Using proportional hazards models, we tested this hypothesis among 545,770 participants in the prospective NIH-AARP Diet and Health Study, which assessed dietary intake at baseline (1995–96) with a comprehensive food frequency questionnaire (FFQ) and at ages 12–13 years with an abbreviated FFQ.
During follow-up through 2003, 585 participants were diagnosed with glioma. We found no significant trends in glioma risk for consumption of processed or red meat, nitrate, or vitamin C or E. We found significant positive trends for nitrite intake from plant sources (hazard ratio [HR] for quintile 5 vs. 1, 1.59; 95% confidence interval [CI], 1.20–2.10; p-trend = 0.028) and, unexpectedly, for fruit and vegetable intake (HR, 1.42; 95% CI, 1.08–1.86; p-trend = .0081). Examination of interactions between dietary intakes (e.g., nitrite and vitamin C) and a limited analysis of diet at ages 12–13 provided no support for the NOC hypothesis.
Our results cast doubt on the NOC hypothesis in relation to dietary intake and adult glioma risk.
Further work is needed on early life diet, adult intake of nitrite from plant sources, and adult intake of fruit and vegetables in relation to adult glioma risk.
glioma; brain cancer; nitrite; nitrate; N-nitroso compounds
Background: Residential proximity to agricultural pesticide applications has been used as a surrogate for exposure in epidemiologic studies, although little is known about the relationship with levels of pesticides in homes.
Objective: We identified determinants of concentrations of agricultural pesticides in dust.
Methods: We collected samples of carpet dust and mapped crops within 1,250 m of 89 residences in California. We measured concentrations of seven pesticides used extensively in agriculture (carbaryl, chlorpyrifos, chlorthal-dimethyl, diazinon, iprodione, phosmet, and simazine). We estimated use of agricultural pesticides near residences from a statewide database alone and by linking the database with crop maps. We calculated the density of pesticide use within 500 and 1,250 m of residences for 180, 365, and 730 days before collection of dust and evaluated relationships between agricultural pesticide use estimates and pesticide concentrations in carpet dust.
Results: For five of the seven pesticides evaluated, residences with use of agricultural pesticides within 1,250 m during the previous 365 days had significantly higher concentrations of pesticides than did residences with no nearby use. The highest correlation with concentrations of pesticides was generally for use reported within 1,250 m of the residence and 730 days before sample collection. Regression models that also accounted for occupational and home use of pesticides explained only a modest amount of the variability in pesticide concentrations (4–28%).
Conclusions: Agricultural pesticide use near residences was a significant determinant of concentrations of pesticides in carpet dust for five of seven pesticides evaluated.
agriculture; dust; exposure; GIS; pesticides
Exploring spatial-temporal patterns of disease incidence through cluster analysis identifies areas of significantly elevated or decreased risk, providing potential clues about disease risk factors. Little is known about the etiology of non-Hodgkin lymphoma (NHL), or the latency period that might be relevant for environmental exposures, and there are no published spatial-temporal cluster studies of NHL.
We conducted a population-based case-control study of NHL in four National Cancer Institute (NCI)-Surveillance, Epidemiology, and End Results (SEER) centers: Detroit, Iowa, Los Angeles, and Seattle during 1998-2000. Using 20-year residential histories, we used generalized additive models adjusted for known risk factors to model spatially the probability that an individual had NHL and to identify clusters of elevated or decreased NHL risk. We evaluated models at five different time periods to explore the presence of clusters in a time frame of etiologic relevance.
The best model fit was for residential locations 20 years prior to diagnosis in Detroit, Iowa, and Los Angeles. We found statistically significant areas of elevated risk of NHL in three of the four study areas (Detroit, Iowa, and Los Angeles) at a lag time of 20 years. The two areas of significantly elevated risk in the Los Angeles study area were detected only at a time lag of 20 years. Clusters in Detroit and Iowa were detected at several time points.
We found significant spatial clusters of NHL after allowing for disease latency and residential mobility. Our results show the importance of evaluating residential histories when studying spatial patterns of cancer.
The incidence of non-Hodgkin lymphoma has substantially increased during the past several decades, and although established risk factors such as immunodeficiency and viral infection may be responsible for a portion of the cases, the vast majority of the NHL cases remain unexplained. Dietary nitrate and nitrite intake are exposures of particular interest for non-Hodgkin lymphoma risk as they have been shown to cause lymphomas in animal studies and there is growing evidence of adverse impact in the epidemiological literature. We investigated NHL risk in general and by subtype in relation to dietary nitrate and nitrite intake in a population-based case-control study of 1,304 women in Connecticut. Nitrate and nitrite intake was assessed using a 120-item food frequency questionnaire. We found no association between risk of NHL and dietary nitrate and a slightly increased risk of NHL for higher dietary nitrite intake (OR = 1.37; 95% CI: 1.04–1.79). The risk was significantly increased for diffuse large B-cell lymphoma (OR = 1.61; 95% CI: 1.08–2.42), follicular lymphoma (OR = 1.61; 95% CI: 1.02–2.54), and T-cell lymphoma (OR = 2.38; 95% CI: 1.12–5.06). Animal products containing nitrite appear to be driving the risk for DLBC lymphoma and follicular lymphoma, whereas the risk for T-cell lymphoma is being driven by plant products. Our results confirm a previous finding for nitrite intake and highlight the importance of evaluating NHL risk by histologic type. We conclude that these results should be replicated in a larger study with data on water consumption as well as diet.
Non-Hodgkin lymphoma; nitrate and nitrite; diet