Exposure to pesticides and risk of Hodgkin lymphoma in an international consortium of agricultural cohorts (AGRICOH).

PURPOSE: Some pesticides may increase the risk of certain lymphoid malignancies, but few studies have examined Hodgkin lymphoma (HL). In this exploratory study, we examined associations between agricultural use of 22 individual active ingredients and 13 chemical groups and HL incidence. METHODS: We used data from three agricultural cohorts participating in the AGRICOH consortium: the French Agriculture and Cancer Cohort (2005-2009), Cancer in the Norwegian Agricultural Population (1993-2011), and the US Agricultural Health Study (1993-2011). Lifetime pesticide use was estimated from crop-exposure matrices or self-report. Cohort-specific covariate-adjusted overall and age-specific (< 40 or ≥ 40 years) hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression and combined using random effects meta-analysis. RESULTS: Among 316 270 farmers (75% male) accumulating 3 574 815 person-years at risk, 91 incident cases of HL occurred. We did not observe statistically significant associations for any of the active ingredients or chemical groups studied. The highest risks of HL overall were observed for the pyrethroids deltamethrin (meta-HR = 1.86, 95% CI 0.76-4.52) and esfenvalerate (1.86, 0.78-4.43), and inverse associations of similar magnitude were observed for parathion and glyphosate. Risk of HL at ≥ 40 years of age was highest for ever-use of dicamba (2.04, 0.93-4.50) and lowest for glyphosate (0.46, 0.20-1.07). CONCLUSION: We report the largest prospective investigation of these associations. Nonetheless, low statistical power, a mixture of histological subtypes and a lack of information on tumour EBV status complicate the interpretability of the results. Most HL cases occurred at older ages, thus we could not explore associations with adolescent or young adult HL. Furthermore, estimates may be attenuated due to non-differential exposure misclassification. Future work should aim to extend follow-up and refine both exposure and outcome classification.

Animal farming and the risk of lymphohaematopoietic cancers: a meta-analysis of three cohort studies within the AGRICOH consortium.

OBJECTIVE: Animal farming entails a variety of potential exposures, including infectious agents, endotoxins and pesticides, which may play a role in the aetiology of lymphohaematopoietic cancers (LHCs). The aim of this study was to assess whether farming specific animal species is associated with the risk of overall LHC or its subtypes. METHODS: Data from three prospective cohort studies in the USA, France and Norway which are part of the Agricultural Cohort consortium and which collected information about animal farming and cancer were used. Analyses included 316 270 farmers and farm workers. Adjusted Cox models were used to investigate the associations of 13 histological subtypes of LHC (n=3282) with self-reported livestock (cattle, pigs and sheep/goats) and poultry (ever/never and numbers raised) farming. Cohort-specific HRs were combined using random-effects meta-analysis. RESULTS: Ever animal farming in general or farming specific animal species was not meta-associated with overall LHC. The risk of myeloid malignancies decreased with increasing number of livestock (p trend=0.01). Increased risk of myeloproliferative neoplasms was seen with increasing number of sheep/goats (p trend <0.01), while a decreased risk was seen with increasing number of livestock (p trend=0.02). Between cohorts, we observed heterogeneity in the association of type of animal farmed and various LHC subtypes. CONCLUSIONS: This large-scale study of three prospective agricultural cohorts showed no association between animal farming and LHC risk, but few associations between specific animal species and LHC subtypes were observed. The observed differences in associations by countries warrant further investigations.

Survival From Childhood Hematological Malignancies in Denmark: Is Survival Related to Family Characteristics?

BACKGROUND: Due to diverse findings as to the role of family factors for childhood cancer survival even within Europe, we explored a nationwide, register-based cohort of Danish children with hematological malignancies. METHODS: All children born between 1973 and 2006 and diagnosed with a hematological malignancy before the age of 20 years (N = 1,819) were followed until 10 years from diagnosis. Kaplan-Meier curves and Cox proportional hazards models estimating hazard ratios (HR) and 95% confidence intervals (CI) were used to assess the impact of family characteristics on overall survival in children with hematological malignancies. RESULTS: Having siblings and increasing birth order were associated with reduced survival from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Associations with AML were strongest and statistically significant. HRs of 1.62 (CI 0.85; 3.09) and 5.76 (CI 2.01; 16.51) were observed for the fourth or later born children with ALL (N = 41) and AML (N = 9), respectively. Children with older parents showed a tendency toward inferior ALL survival, while for AML young maternal age was related to poorer survival. Based on small numbers, a trend toward poorer survival from non-Hodgkin lymphoma was observed for children having siblings and for children of younger parents. CONCLUSIONS: Further research is warranted to gain further knowledge on the impact of family factors on childhood cancer survival in other populations and to elaborate potential underlying mechanisms and pathways of those survival inequalities.

Assessment of occupational exposure to pesticides in a pooled analysis of agricultural cohorts within the AGRICOH consortium.

BACKGROUND: This paper describes methods developed to assess occupational exposure to pesticide active ingredients and chemical groups, harmonised across cohort studies included in the first AGRICOH pooling project, focused on the risk of lymph-haematological malignancies. METHODS: Three prospective agricultural cohort studies were included: US Agricultural Health Study (AHS), French Agriculture and Cancer Study (AGRICAN) and Cancer in the Norwegian Agricultural Population (CNAP). Self-reported pesticide use was collected in AHS. Crop-exposure matrices (CEMs) were developed for AGRICAN and CNAP. We explored the potential impact of these differences in exposure assessment by comparing a CEM approach estimating exposure in AHS with self-reported pesticide use. RESULTS: In AHS, 99% of participants were considered exposed to pesticides, 68% in AGRICAN and 63% in CNAP. For all cohorts combined (n=316 270), prevalence of exposure ranged from 19% to 59% for 14 chemical groups examined, and from 13% to 46% for 33 active ingredients. Exposures were highly correlated within AGRICAN and CNAP where CEMs were applied; they were less correlated in AHS. Poor agreement was found between self-reported pesticide use and assigned exposure in AHS using a CEM approach resembling the assessment for AGRICAN (κ -0.00 to 0.33) and CNAP (κ -0.01 to 0.14). CONCLUSIONS: We developed country-specific CEMs to assign occupational exposure to pesticides in cohorts lacking self-reported data on the use of specific pesticides. The different exposure assessment methods applied may overestimate or underestimate actual exposure prevalence, and additional work is needed to better estimate how far the exposure estimates deviate from reality.

Birth order and risk of childhood cancer in the Danish birth cohort of 1973-2010.

PURPOSE: Many studies have investigated the possible association between birth order and risk of childhood cancer, although the evidence to date has been inconsistent. Birth order has been used as a marker for various in utero or childhood exposures and is relatively straightforward to assess. METHODS: Data were obtained on all children born in Denmark between 1973 and 2010, involving almost 2.5 million births and about 5,700 newly diagnosed childhood cancers before the age of 20 years. Data were analyzed using Poisson regression models. RESULTS: We failed to observe associations between birth order and risk of any childhood cancer subtype, including acute lymphoblastic leukemia; all rate ratios were close to one. Further analyses stratified by birth cohort (those born between 1973 and 1990, and those born between 1991 and 2010) also failed to show any associations. Considering stillbirths and/or controlling for birth weight and parental age in the analyses had no effect on the results. Analyses by years of birth (those born between 1973 and 1990, and those born between 1991 and 2010) did not show any changes in the overall pattern of no association. CONCLUSIONS: In this large cohort of all children born in Denmark over an almost 40-year period, we did not observe an association between birth order and the risk of childhood cancer.

Cancer mortality in chrysotile miners and millers, Russian Federation: main results (Asbest Chrysotile Cohort-Study).

BACKGROUND: We investigated mortality in workers of the world's largest chrysotile mine and enrichment factories located in the town of Asbest, Russian Federation. METHODS: This historical cohort study included all workers employed for at least 1 year between 1975 and 2010 and follow-up until the end of 2015. Cumulative exposure to dust was estimated based on workers' complete occupational history linked to dust measurements systematically collected from the 1950s. Exposure to chrysotile fibers was estimated using dust-to-fiber conversion factors. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated as mortality rate ratios in Poisson regression models. RESULTS: A total of 30 445 (32% women) workers accumulated 721 312 person-years at risk and 11 110 (36%) died. Of the workers, 54% had more than 30 years since their first exposure. We found an exposure-response between cumulative dust and lung cancer mortality in men. No clear association with dust exposure but a modest increase in the highest category of fiber exposure was seen for lung cancer in women. Mesothelioma mortality was increased (RR = 7.64, 95% CI = 1.18 to 49.5, to at least 80 fibers per cm3 years and RR = 4.56, 95% CI = 0.94 to 22.1, to at least 150 mg/m3 years [dust]), based on 13 deaths. For colorectal and stomach cancer, there were inconsistent associations. No associations were seen for laryngeal or ovarian cancer. CONCLUSION: In this large-scale epidemiological study in the world's largest active asbestos mine, we confirmed an increased risk of mesothelioma with high fiber exposure and an increasing mortality for lung cancer in men with increasing dust exposure. Less clear-cut increased lung cancer mortality was seen in the women. Continued mortality follow-up is warranted.

Does a more refined assessment of exposure to bitumen fume and confounders alter risk estimates from a nested case-control study of lung cancer among European asphalt workers?

OBJECTIVE: To investigate whether a refined assessment of exposure to bitumen fume among workers in the European asphalt industry within a nested case-control study resulted in a different interpretation pertaining to risk of lung cancer mortality compared with the cohort study. METHODS: Pearson correlation coefficients between refined and original estimates were calculated. Logistic regression and generalised additive models (penalised splines) were fitted to estimate ORs for exposure to bitumen fume using the refined and original exposure estimates, respectively, while adjusting for potential confounding. RESULTS: 1555 subjects included in the nested case-control study had both refined and original estimates for exposure to bitumen fume. Exposure assessment in the nested case-control study (compared with the cohort phase) increased the number of subjects never-exposed to bitumen fume from 18% to 32%. From the 1282 subjects originally considered exposed in the cohort phase, 309 (24%) became unexposed after the nested case-control exposure assessment. From the 273 subjects originally considered non-exposed in the cohort phase, 87 (32%) became exposed in the nested case-control study. The majority (75%) of subjects however did not change exposure status and changes were similar among cases and controls. Correlation coefficients between refined and original exposure estimates were moderate overall (range 0.42-0.46), but varied considerably among countries. The ORs and exposure-response curves for exposure to bitumen fume were not meaningfully different between analyses that used refined and original exposure estimates. Adjustment for tobacco smoking and exposure to coal tar did not change these patterns. CONCLUSIONS: Our results showed that more detailed data collection and exposure assessment in the nested case-control study compared with the cohort study did change exposure status of many subjects, but did not alter results of the exposure-response analysis. Adjustment for tobacco smoking did not have a noticeable effect on risk estimates either.

Risk of hematological malignancies from CT radiation exposure in children, adolescents and young adults.

Over one million European children undergo computed tomography (CT) scans annually. Although moderate- to high-dose ionizing radiation exposure is an established risk factor for hematological malignancies, risks at CT examination dose levels remain uncertain. Here we followed up a multinational cohort (EPI-CT) of 948,174 individuals who underwent CT examinations before age 22 years in nine European countries. Radiation doses to the active bone marrow were estimated on the basis of body part scanned, patient characteristics, time period and inferred CT technical parameters. We found an association between cumulative dose and risk of all hematological malignancies, with an excess relative risk of 1.96 (95% confidence interval 1.10 to 3.12) per 100 mGy (790 cases). Similar estimates were obtained for lymphoid and myeloid malignancies. Results suggest that for every 10,000 children examined today (mean dose 8 mGy), 1-2 persons are expected to develop a hematological malignancy attributable to radiation exposure in the subsequent 12 years. Our results strengthen the body of evidence of increased cancer risk at low radiation doses and highlight the need for continued justification of pediatric CT examinations and optimization of doses.

TP53 R249S mutation, genetic variations in HBX and risk of hepatocellular carcinoma in The Gambia.

In regions with high prevalence of chronic hepatitis B virus (HBV) infection and dietary aflatoxin B(1) (AFB(1)) exposure, hepatocellular carcinomas (HCCs) often contain TP53 mutation at codon 249 (R249S). Furthermore, a C-terminal truncated HBx protein expressed from hepatocyte integrated HBV is associated with HCC development. This study evaluates the association between R249S and HBX status in relation to HCC in West African population. HBX (complete or 3'-truncated) and HBS genes were assessed by PCR in cell-free DNA (CFDNA) from plasma of subjects recruited in a hospital-based case-control study (325 controls, 78 cirrhotic patients and 198 HCC cases) conducted in The Gambia. These samples had been previously analyzed for R249S and HBV serological status. Complete HBX sequence was frequently detected in CFDNA of HCC-R249S positive (77%, 43/56) compared with HCC-R249S-negative cases (44%, 22/50). Conversely, the proportion of 3'-truncated HBX gene was significantly higher in HCC-R249S negative than positive cases (34%, 17/50, compared with 12%, 7/56) (χ(2) = 12.12; P = 0.002; distribution of R249S negative and positive according to HBX status). Occult HBV infection (detected by PCR) was present in 24% of HCC previously considered as negative by HBV serology. Moreover, HBV mutation analysis revealed that double mutation at nucleotides 1762(T)/1764(A) was associated with diagnosis of cirrhosis or HCC {cirrhosis: odds ratio (OR): 9.50 [95% confidence interval (CI) 1.50-60.11]; HCC: OR: 11.29 [95% CI 2.07-61.47]}. These findings suggest that in HCC from The Gambia, complete HBX sequences are often associated with the presence of TP53 R249S mutation.

Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium.

To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 case-control studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR = 0.76, 95% CI = 0.59-0.96) and with ever use of calcium supplement (OR = 0.64, 95% CI = 0.42-0.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR = 0.72, 95% CI = 0.54-0.97) and more than 365 tablets of cumulative calcium intake (OR = 0.36, 95% CI = 0.16-0.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of HNC.

Second primary malignancies among women with uterine sarcoma.

OBJECTIVE: Uterine sarcomas (US) are rare malignancies with unclear aetiology. Studies on uterine sarcomas in the setting of second primary malignant tumours can provide clues to aetiology and identify side effects of different treatments. METHODS: A cohort of 8606 cases of US was extracted from the data from 13 cancer registries and followed for second primary cancers within the period 1943-2000. Standardized incidence ratios (SIRs) were calculated, and Poisson regression analyses were performed. RESULTS: There were 499 cancer cases observed after a first diagnosis of US (SIR 1.26, 95%CI 1.16-1.38). SIRs were elevated for cancers of the mouth and pharynx (2.16, 95%CI 1.15-3.69), colorectum (1.60, 95%CI 1.28-1.98), lung (1.73, 95%CI 1.27-2.29), breast (1.25, 95%CI 1.05-1.49), urinary bladder (1.74, 95%CI 1.02-2.79), kidney (2.00, 95%CI 1. 24-3.06), thyroid gland (2.74, 95%CI 1.42-4.79), and soft tissue sarcoma (5.23, 95%CI 2.51-9.62). The risk of breast cancer increased along with increasing age of US diagnosis (p trend 0.040). The risk of kidney cancer increased along with decreasing age of US diagnosis (p trend 0.004) and short time since the US diagnosis (p trend 0.018). CONCLUSIONS: Our study demonstrated increased risk of certain cancers following a diagnosis of US. The elevated risk for breast cancer may indicate shared hormonal aetiology, while the increased risk of colorectal and bladder cancers after US may be caused by radiation therapy of US. The clustering of smoking-related cancers after US is worth exploring in the future.

Occupational exposure to arsenic, cadmium, chromium, lead and nickel, and renal cell carcinoma: a case-control study from Central and Eastern Europe.

OBJECTIVES: To investigate the risk of renal cell carcinoma (RCC) in Central and Eastern Europe in relation to exposure to known and suspected carcinogenic metals. METHODS: During 1999-2003, the authors conducted a hospital-based study in Czech Republic, Poland, Romania and Russia, including 1097 cases of RCC and 1476 controls. Occupational exposure to arsenic, cadmium, chromium(III), chromium(VI), lead and nickel was assessed by teams of local industrial hygiene experts, based on detailed occupational questionnaires. RESULTS: The ORs for RCC were 1.55 (95% CI 1.09 to 2.21) for exposure to lead and 1.40 (95% CI 0.69 to 2.85) for exposure to cadmium. No clear monotonic exposure-response relation was apparent for either duration of exposure or cumulative exposure to either metal, although the OR for the highest category of cumulative exposure to lead was 2.25 (95% CI 1.21 to 4.19). Exposure to other metals did not entail an increased risk of RCC. CONCLUSIONS: For cadmium, the lack of statistical significance of most results, potential confounding and the absence of clear dose-response relations suggest that an association with RCC is unlikely to be causal. In the case of lead, however, the elevated risk in the category of highest cumulative exposure is noteworthy and justifies further investigation.

Cancer incidence in agricultural workers: Findings from an international consortium of agricultural cohort studies (AGRICOH).

BACKGROUND: Agricultural work can expose workers to potentially hazardous agents including known and suspected carcinogens. This study aimed to evaluate cancer incidence in male and female agricultural workers in an international consortium, AGRICOH, relative to their respective general populations. METHODS: The analysis included eight cohorts that were linked to their respective cancer registries: France (AGRICAN: n = 128,101), the US (AHS: n = 51,165, MESA: n = 2,177), Norway (CNAP: n = 43,834), Australia (2 cohorts combined, Australian Pesticide Exposed Workers: n = 12,215 and Victorian Grain Farmers: n = 919), Republic of Korea (KMCC: n = 8,432), and Denmark (SUS: n = 1,899). For various cancer sites and all cancers combined, standardized incidence ratios (SIR) and 95% confidence intervals (CIs) were calculated for each cohort using national or regional rates as reference rates and were combined by random-effects meta-analysis. RESULTS: During nearly 2,800,000 person-years, a total of 23,188 cancers were observed. Elevated risks were observed for melanoma of the skin (number of cohorts = 3, meta-SIR = 1.18, CI: 1.01-1.38) and multiple myeloma (n = 4, meta-SIR = 1.27, CI: 1.04-1.54) in women and prostate cancer (n = 6, meta-SIR = 1.06, CI: 1.01-1.12), compared to the general population. In contrast, a deficit was observed for the incidence of several cancers, including cancers of the bladder, breast (female), colorectum, esophagus, larynx, lung, and pancreas and all cancers combined (n = 7, meta-SIR for all cancers combined = 0.83, 95% CI: 0.77-0.90). The direction of risk was largely consistent across cohorts although we observed large between-cohort variations in SIR for cancers of the liver and lung in men and women, and stomach, colorectum, and skin in men. CONCLUSION: The results suggest that agricultural workers have a lower risk of various cancers and an elevated risk of prostate cancer, multiple myeloma (female), and melanoma of skin (female) compared to the general population. Those differences and the between-cohort variations may be due to underlying differences in risk factors and warrant further investigation of agricultural exposures.

Dose Estimation for the European Epidemiological Study on Pediatric Computed Tomography (EPI-CT).

Within the European Epidemiological Study to Quantify Risks for Paediatric Computerized Tomography (EPI-CT study), a cohort was assembled comprising nearly one million children, adolescents and young adults who received over 1.4 million computed tomography (CT) examinations before 22 years of age in nine European countries from the late 1970s to 2014. Here we describe the methods used for, and the results of, organ dose estimations from CT scanning for the EPI-CT cohort members. Data on CT machine settings were obtained from national surveys, questionnaire data, and the Digital Imaging and Communications in Medicine (DICOM) headers of 437,249 individual CT scans. Exposure characteristics were reconstructed for patients within specific age groups who received scans of the same body region, based on categories of machines with common technology used over the time period in each of the 276 participating hospitals. A carefully designed method for assessing uncertainty combined with the National Cancer Institute Dosimetry System for CT (NCICT, a CT organ dose calculator), was employed to estimate absorbed dose to individual organs for each CT scan received. The two-dimensional Monte Carlo sampling method, which maintains a separation of shared and unshared error, allowed us to characterize uncertainty both on individual doses as well as for the entire cohort dose distribution. Provided here are summaries of estimated doses from CT imaging per scan and per examination, as well as the overall distribution of estimated doses in the cohort. Doses are provided for five selected tissues (active bone marrow, brain, eye lens, thyroid and female breasts), by body region (i.e., head, chest, abdomen/pelvis), patient age, and time period (1977-1990, 1991-2000, 2001-2014). Relatively high doses were received by the brain from head CTs in the early 1990s, with individual mean doses (mean of 200 simulated values) of up to 66 mGy per scan. Optimization strategies implemented since the late 1990s have resulted in an overall decrease in doses over time, especially at young ages. In chest CTs, active bone marrow doses dropped from over 15 mGy prior to 1991 to approximately 5 mGy per scan after 2001. Our findings illustrate patterns of age-specific doses and their temporal changes, and provide suitable dose estimates for radiation-induced risk estimation in epidemiological studies.

Dietary patterns and risk of advanced prostate cancer: a principal component analysis in Uruguay.

OBJECTIVE: In order to explore the role of broader eating patterns in the etiology of prostate cancer, we conducted a principal components analysis among Uruguayan men. METHODS: The study included 345 newly diagnosed cases of advanced prostate cancer and 690 hospitalized controls. The factor analysis was performed using the control population. RESULTS: Factor analysis allowed the extraction of five patterns, labeled as prudent, traditional, substituter, drinker, and Western. Whereas the traditional and Western patterns were directly associated with risk of prostate cancer (OR for high quartile versus the low quartile of the Western diet was 2.35, 95% CI 1.44-3.85, p-value for trend < 0.0001), the prudent, drinker, and substituter patterns were not associated with risk of the disease. After adjustment of each pattern for the foods with high loadings, these three patterns did not modify substantially their original ORs. CONCLUSION: The Western and traditional patterns could partially explain the high incidence of advanced prostate cancer in Uruguay, a main producer of beef in the World.

Exposure assessment for a nested case-control study of lung cancer among European asphalt workers.

OBJECTIVE: Development of a method for retrospective assessment of exposure to bitumen fume, bitumen condensate, organic vapour, polycyclic aromatic hydrocarbons, and co-exposures to known or suspected lung carcinogens for a nested case-control study of lung cancer mortality among European asphalt workers. METHODS: Company questionnaires and structured questionnaires used in interviews and industry-specific job-exposure matrices (JEMs) were elaborated and applied. Three sources of information were eventually used for exposure assessment and assignment: (i) data obtained in cohort phase, (ii) data from living subjects, next-of-kin, and fellow-workers questionnaires, and (iii) JEMs for bitumen exposure by inhalation and via skin and co-exposures to known or suspected lung carcinogens within and outside cohort companies. Inhalation and dermal exposure estimates for bitumen were adjusted for time trends, time spent in a job, and other determinants of exposure (e.g. oil gravel paving). Clothing patterns, personal protective devices, and personal hygiene were taken into consideration while estimating dermal exposure. RESULTS: Occupational exposures could be assessed for 433 cases and 1253 controls for relevant time periods. Only 43% of work histories were spent inside original asphalt and construction companies. A total of 95.8% of job periods in cohort companies could be coded at a more detailed level. Imputation of work time and 'hygienic behaviour' multipliers was needed for <10% of work history years. Overall, downward trends in exposure were present and differences existed between countries and companies. As expected, correlations were strongest (r > 0.7) among bitumen-related agents, while correlations between coal tar, bitumen-related agents, and established lung carcinogens were weaker (r < 0.4). CONCLUSIONS: A systematic and detailed approach was developed to estimate inhalation and dermal exposure for a nested case-control study among asphalt workers.

Dietary patterns and risk of cancer: a factor analysis in Uruguay.

A multisite case-control study on factor analysis and several cancer sites (mouth and pharynx, esophagus, stomach, colon, rectum, larynx, lung, breast, prostate, bladder, kidney) was conducted in Uruguay. The study included 3,528 cases and 2,532 controls. Factor analysis (principal components) was modeled among controls. This patterning method retained 4 factors per sex, labeled as prudent, drinker, traditional and Western. Odds ratios for these cancer sites, stratified by sex, were estimated using polytomous regression. Whereas the prudent pattern was mainly negatively associated with cancers of the upper aerodigestive tract, the Western pattern showed a strong increase in breast, lung and colon cancers. The study allowed for the reproducibility of the prudent, drinker and Western patterns, whereas the traditional pattern appears to be country specific.

Family history of cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

Alcohol and tobacco consumption are well-recognized risk factors for head and neck cancer (HNC). Evidence suggests that genetic predisposition may also play a role. Only a few epidemiologic studies, however, have considered the relation between HNC risk and family history of HNC and other cancers. We pooled individual-level data across 12 case-control studies including 8,967 HNC cases and 13,627 controls. We obtained pooled odds ratios (OR) using fixed and random effect models and adjusting for potential confounding factors. All statistical tests were two-sided. A family history of HNC in first-degree relatives increased the risk of HNC (OR=1.7, 95% confidence interval, CI, 1.2-2.3). The risk was higher when the affected relative was a sibling (OR=2.2, 95% CI 1.6-3.1) rather than a parent (OR=1.5, 95% CI 1.1-1.8) and for more distal HNC anatomic sites (hypopharynx and larynx). The risk was also higher, or limited to, in subjects exposed to tobacco. The OR rose to 7.2 (95% CI 5.5-9.5) among subjects with family history, who were alcohol and tobacco users. A weak but significant association (OR=1.1, 95% CI 1.0-1.2) emerged for family history of other tobacco-related neoplasms, particularly with laryngeal cancer (OR=1.3, 95% CI 1.1-1.5). No association was observed for family history of nontobacco-related neoplasms and the risk of HNC (OR=1.0, 95% CI 0.9-1.1). Familial factors play a role in the etiology of HNC. In both subjects with and without family history of HNC, avoidance of tobacco and alcohol exposure may be the best way to avoid HNC.

Type of alcoholic beverage and risk of head and neck cancer--a pooled analysis within the INHANCE Consortium.

The authors pooled data from 15 case-control studies of head and neck cancer (9,107 cases, 14,219 controls) to investigate the independent associations with consumption of beer, wine, and liquor. In particular, they calculated associations with different measures of beverage consumption separately for subjects who drank beer only (858 cases, 986 controls), for liquor-only drinkers (499 cases, 527 controls), and for wine-only drinkers (1,021 cases, 2,460 controls), with alcohol never drinkers (1,124 cases, 3,487 controls) used as a common reference group. The authors observed similar associations with ethanol-standardized consumption frequency for beer-only drinkers (odds ratios (ORs) = 1.6, 1.9, 2.2, and 5.4 for < or =5, 6-15, 16-30, and >30 drinks per week, respectively; P(trend) < 0.0001) and liquor-only drinkers (ORs = 1.6, 1.5, 2.3, and 3.6; P < 0.0001). Among wine-only drinkers, the odds ratios for moderate levels of consumption frequency approached the null, whereas those for higher consumption levels were comparable to those of drinkers of other beverage types (ORs = 1.1, 1.2, 1.9, and 6.3; P < 0.0001). Study findings suggest that the relative risks of head and neck cancer for beer and liquor are comparable. The authors observed weaker associations with moderate wine consumption, although they cannot rule out confounding from diet and other lifestyle factors as an explanation for this finding. Given the presence of heterogeneity in study-specific results, their findings should be interpreted with caution.