Search

Background: Occupational exposure to acrylamide was associated with excess mortality from pancreatic cancer, though in the absence of dose-risk relationship. Few epidemiological studies have examined the association between acrylamide from diet and pancreatic cancer risk. Patients and methods: We considered this issue in a combined set of 1975 cases of pancreatic cancer and 4239 controls enrolled in six studies of the Pancreatic Cancer Case-Control Consortium (PanC4). We calculated pooled odds ratios (ORs) and their 95% confidence intervals (CI) by estimating study-specific ORs through multivariate unconditional logistic regression models and pooling the obtained estimates using random-effects models. Results: Compared with the lowest level of estimated dietary acrylamide intake, the pooled ORs were 0.97 (95% CI, 0.79-1.19) for the second, 0.91 (95% CI, 0.71-1.16) for the third, and 0.92 (95% CI, 0.66-1.28) for the fourth (highest) quartile of intake. For an increase of 10 mg/day of acrylamide intake, the pooled OR was 0.96 (95% CI, 0.87-1.06), with heterogeneity between estimates (I2 = 67%). Results were similar across various subgroups, and were confirmed when using a one-stage modelling approach. Conclusions: This PanC4 pooled-analysis found no association between dietary acrylamide and pancreatic cancer. © The Author 2016.

Lucenteforte, E La Vecchia, C Silverman, D Petersen, G M Bracci, P M Ji, B T Bosetti, C Li, D Gallinger, S Miller, A B Bueno-de-Mesquita, H B Talamini, R Polesel, J Ghadirian, P Baghurst, P A Zatonski, W Fontham, E Bamlet, W R Holly, E A Gao, Y T Negri, E Hassan, M Cotterchio, M Su, J Maisonneuve, P Boffetta, P Duell, E J eng CA098889/CA/NCI NIH HHS/ CA108370/CA/NCI NIH HHS/ CA109767/CA/NCI NIH HHS/ CA59706/CA/NCI NIH HHS/ CA89726/CA/NCI NIH HHS/ N01-CP-05225/CP/NCI NIH HHS/ N01-CP-05227/CP/NCI NIH HHS/ N01-CP-31022/CP/NCI NIH HHS/ N01-CP-51089/CP/NCI NIH HHS/ N01-CP-51090/CP/NCI NIH HHS/ N01-CP-51092/CP/NCI NIH HHS/ N01-PC-35136/PC/NCI NIH HHS/ Meta-Analysis Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't England 2011/05/04 06:00 Ann Oncol. 2012 Feb;23(2):374-82. doi: 10.1093/annonc/mdr120. Epub 2011 May 2.; International audience; BACKGROUND: Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved. METHODS: To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled analysis of 10 case-control studies (5585 cases and 11,827 controls) participating in the International Pancreatic Cancer Case-Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models. RESULTS: Compared with abstainers and occasional drinkers (< 1 drink per day), we observed no association for light-to-moderate alcohol consumption (/= 9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area. CONCLUSION: This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.

Experimental evidence suggests that parental exposure to polycyclic aromatic hydrocarbons (PAH), which occurs primarily through tobacco smoke, occupational exposure, and air pollution, could increase the risk of cancer during childhood. Population-based case-control studies carried out in seven countries as part of the SEARCH Program compared data for 1,218 cases of childhood brain tumors and 2,223 controls (1976-1994). Parental occupational exposure to PAH during the 5-year period before birth was estimated with a job exposure matrix. Risk estimates were adjusted for child's age, sex, and study center. Paternal preconceptional occupational exposure to PAH was associated with increased risks of all childhood brain tumors (odds ratio (OR) = 1.3, 95% confidence interval: 1.1, 1.6) and astroglial tumors (OR = 1.4, 95% confidence interval: 1.1, 1.7). However, there was no trend of increasing risk with predicted level of exposure. Paternal smoking alone (OR = 1.4) was also associated with the risk of astroglial tumors in comparison with nonsmoking, non-occupationally-exposed fathers. Risks for paternal occupational exposure were higher, with (OR = 1.6) or without (OR = 1.7) smoking. Maternal occupational exposure to PAH before conception or during pregnancy was rare, and this exposure was not associated with any type of childhood brain tumor. This large study supports the hypothesis that paternal preconceptional exposure to PAH increases the risk of brain tumors in humans.

BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for =15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for

Objective: To evaluate the role of parental occupations in the etiology of childhood brain tumors (CBT).

To evaluate the risk of childhood brain tumor occurrence in relation to epilepsy and anticonvulsant use.As part of a multicenter case-control study of pediatric brain tumors, maternal report on epilepsy occurrence before diagnosis of her child's brain tumor was collected for 540 cases and compared with 801 control children. Mothers also reported on any long-term (or = 2 weeks) use of medications by her child before the date of tumor diagnosis (or a comparable reference date for controls) and these medications were classified according to whether they contained barbiturates.As expected, because seizures are often an early brain tumor symptom, a strong association was observed between epilepsy and brain tumor occurrence (odds ratio, OR = 6.2; 95% confidence limit, CL = 2.9, 14). The association remained elevated even after aor = 10-year interval between diagnoses of epilepsy and brain tumor (OR = 4.7; CL = 0.8, 48). Elevated odds ratios were observed both for epileptic children who were treated with anticonvulsants containing barbiturates (OR = 5.8; CL = 2.2, 18) and for those not treated with barbiturates (OR = 7.9; CL = 1.7, 74), relative to nonepileptic children.Whereas most of the brain tumor risk associated with epilepsy may be due to occult tumors, the finding of an elevated risk many years after diagnosis of epilepsy is of interest.

Bosetti, C Lucenteforte, E Bracci, P M Negri, E Neale, R E Risch, H A Olson, S H Gallinger, S Miller, A B Bueno-de-Mesquita, H B Talamini, R Polesel, J Ghadirian, P Baghurst, P A Zatonski, W Fontham, E Holly, E A Gao, Y T Yu, H Kurtz, R C Cotterchio, M Maisonneuve, P Zeegers, M P Duell, E J Boffetta, P La Vecchia, C eng 5R01-CA098870/CA/NCI NIH HHS/ CA098889/CA/NCI NIH HHS/ CA108370/CA/NCI NIH HHS/ CA109767/CA/NCI NIH HHS/ CA59706/CA/NCI NIH HHS/ CA89726/CA/NCI NIH HHS/ N01-PC-35136/PC/NCI NIH HHS/ R01 CA97075/CA/NCI NIH HHS/ U01 CA074783/CA/NCI NIH HHS/ U01-CA74783/CA/NCI NIH HHS/ U24 CA074783/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2013/08/24 06:00 Ann Oncol. 2013 Nov;24(11):2903-10. doi: 10.1093/annonc/mdt336. Epub 2013 Aug 22.; International audience; BACKGROUND: Peptic ulcer and its treatments have been associated to pancreatic cancer risk, although the evidence is inconsistent. METHODS: We pooled 10 case-control studies within the Pancreatic Cancer Case-control Consortium (PanC4), including 4717 pancreatic cancer cases and 9374 controls, and estimated summary odds ratios (OR) using multivariable logistic regression models. RESULTS: The OR for pancreatic cancer was 1.10 [95% confidence interval (CI) 0.98-1.23] for history of ulcer (OR = 1.08 for gastric and 0.97 for duodenal ulcer). The association was stronger for a diagnosis within 2 years before cancer diagnosis (OR = 2.43 for peptic, 1.75 for gastric, and 1.98 for duodenal ulcer). The OR was 1.53 (95% CI 1.15-2.03) for history of gastrectomy; however, the excess risk was limited to a gastrectomy within 2 years before cancer diagnosis (OR = 6.18, 95% CI 1.82-20.96), while no significant increased risk was observed for longer time since gastrectomy. No associations were observed for pharmacological treatments for ulcer, such as antacids, H2-receptor antagonists, or proton-pump inhibitors. CONCLUSIONS: This uniquely large collaborative study does not support the hypothesis that peptic ulcer and its treatment materially affect pancreatic cancer risk. The increased risk for short-term history of ulcer and gastrectomy suggests that any such association is due to increased cancer surveillance.

We conducted a case-control study in the western United States to determine the relation between occupations or chemical exposures and increased risk of uveal melanoma. Among men (221 patients, 447 controls), we found increased risks for occupational groups who had intense exposure to ultraviolet light [odds ratio (OR) = 3.0; 95% confidence interval (CI) = 1.2-7.8], welding exposure (OR = 2.2; 95% CI = 1.3-3.5), and asbestos exposure (OR = 2.4; 95% CI = 1.5-3.9 for most likely exposed). The highest odds ratio was for the small number of men (nine cases, three controls) who were chemists, chemical engineers, and chemical technicians (OR = 5.9; 95% CI = 1.6-22.7). Odds ratios also were elevated for exposures to antifreeze, formaldehyde, pesticides, and carbon tetrachloride, but these findings, based on recall of specific chemical exposures, are more subject to recall bias than the findings based on occupational groups.

Background Non-Hodgkin lymphoma (NHL) subtypes, diffuse large B-cell (DLBCL) and follicular lymphoma (FL) have different sex ratios and are diagnosed at ages over 60 years; DLBCL is more common in men and diagnosed at older ages than FL, which occurs more among women. This analysis of postmenopausal women examines the relationship between postmenopausal hormone therapy and NHL. Design Self-reported use of postmenopausal hormone therapy from 2094 postmenopausal women with NHL and 2731 without were pooled across nine case–control studies (1983–2005) from North America, Europe and Japan. Study-specific odds ratios (OR) and 95% confidence intervals (CI) estimated using logistic regression were pooled using random-effects meta-analyses. Results Postmenopausal women who used hormone therapy were at decreased risk of NHL (pooled OR = 0.79, 95% CI 0.69–0.90). Risks were reduced when the age of starting was 50 years or older. There was no clear trend with number of years of use. Current users were at decreased risk while those stopping over 2 years before diagnosis were not. Having a hysterectomy or not did not affect the risk. Favourable effects were present for DLBCL (pooled OR = 0.66, 95% CI 0.54–0.80) and FL (pooled OR = 0.82, 95% CI 0.66–1.01). Conclusion Postmenopausal hormone therapy, particularly used close to menopause, is associated with a decreased risk of NHL.

Background: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. Patients and methods: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10 947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). Results: The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of =2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (=65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). Conclusions: Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Bosetti, C Lucenteforte, E Silverman, D T Petersen, G Bracci, P M Ji, B T Negri, E Li, D Risch, H A Olson, S H Gallinger, S Miller, A B Bueno-de-Mesquita, H B Talamini, R Polesel, J Ghadirian, P Baghurst, P A Zatonski, W Fontham, E Bamlet, W R Holly, E A Bertuccio, P Gao, Y T Hassan, M Yu, H Kurtz, R C Cotterchio, M Su, J Maisonneuve, P Duell, E J Boffetta, P La Vecchia, C eng 5R01-CA098870/CA/NCI NIH HHS/ CA098889/CA/NCI NIH HHS/ CA108370/CA/NCI NIH HHS/ CA109767/CA/NCI NIH HHS/ CA59706/CA/NCI NIH HHS/ CA89726/CA/NCI NIH HHS/ N01-CP-05225/CP/NCI NIH HHS/ N01-CP-05227/CP/NCI NIH HHS/ N01-CP-31022/CP/NCI NIH HHS/ N01-CP-51089/CP/NCI NIH HHS/ N01-CP-51090/CP/NCI NIH HHS/ N01-CP-51092/CP/NCI NIH HHS/ N01-PC-35136/PC/NCI NIH HHS/ P50 CA102701/CA/NCI NIH HHS/ R01 CA97075/CA/NCI NIH HHS/ Canadian Institutes of Health Research/Canada Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2011/11/23 06:00 Ann Oncol. 2012 Jul;23(7):1880-8. doi: 10.1093/annonc/mdr541. Epub 2011 Nov 21.; International audience; BACKGROUND: To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables. METHODS: We analyzed data from 12 case-control studies within the International Pancreatic Cancer Case-Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models. RESULTS: Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0-1.3) for former smokers and 2.2 (95% CI 1.7-2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR=3.4 for >/=35 cigarettes per day, P for trend

Background: Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco. Materials and methods: We conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case-control studies (6056 cases and 11 338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates. Results: Compared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2-2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4-1.6). The OR was 1.1 (95% CI 0.69-1.6) for pipeonly smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for = 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75-1.3). Conclusion: This collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Data from 1218 cases of childhood brain tumors (CBT) diagnosed between 1976 and 1994 and 2223 matched controls from the general population were included in an analysis of maternal beauty product exposure and beauty-related employment in 9 centers in 7 countries. A 50% increased odds ratio (OR) [95% confidence interval (CI) = 1.0–2.1] for CBT was observed among children of mothers who were exposed via personal use of and/or possible ambient contact with beauty products during the 5 years preceding the index child’s birth compared with children of mothers never exposed to beauty products during this time period. Overall maternal personal use of hair-coloring agents in the month before or during the pregnancy of the index child’s birth was not associated with CBT (OR = 1.0, CI = 0.83–1.3) or with astroglial (OR = 1.1, CI = 0.85–1.4), PNET (OR = 1.0, CI = 0.71–1.5) and other glial subtypes (OR = 1.0, CI = 0.62–1.0). Similarly, no statistically increased ORs or discernable pattern of risk estimates were observed for period of use or for number of applications per year for maternal personal use of hair-coloring agents overall or by histologic type. Among children born on or after 1980, increased ORs for CBT were associated with maternal non-work-related exposure to any beauty products (OR = 2.6, CI = 1.2–5.9), hair-dyes (OR = 11, CI = 1.2–90), and hair sprays (OR = 3.4, CI = 1.0–11). No overall increased OR for CBT was observed among children of mothers employed in beauty-related jobs during the 5 years preceding the index child’s birth compared with those who reported no beauty-related employment. In general, other specific beauty product-related exposures were not associated with increased ORs for CBT. Data from our study provide little evidence of an increased risk for CBT with mothers’ exposures to beauty products.

Pancreatic cancer is a highly fatal cancer with few identified risk factors. Increased risk of pancreatic cancer in tobacco smokers and among diabetic patients is well established, and some reports have suggested associations with coffee consumption and occupational exposure to organochlorines. At present, there is little information regarding the possible association of these risk factors with the known genetic alterations found in pancreatic cancers, such as activation of the K-ras oncogene and inactivation of the p53 tumor suppressor gene. Knowledge of such relationships may help to understand the molecular pathways of pancreatic tumorigenesis. We investigated the association between these molecular defects and risk factors for pancreatic cancer in 61 newly diagnosed patients identified through an ongoing study of pancreatic cancer in the San Francisco Bay Area. Interview information was obtained regarding environmental exposures, medical history, and demographic factors. Serum levels of dichlorodiphenyltrichloroethylene (DDE) and polychlorinated biphenyls were available on a subset of 24 patients. Tumor blocks were located from local hospitals and used for K-ras mutational analysis at codon 12 and for p53 protein immunohistochemistry. The molecular analyses were facilitated through the use of laser capture microdissection, which provides a reliable method to obtain almost pure populations of tumor cells. Mutations in K-ras codon 12 were found in 46 (75%) of 61 pancreatic cancers. A prior diagnosis of diabetes was significantly associated with K-ras negative tumors (P = 0.002, Fisher's exact test). The absence of this mutation was also associated with increased serum levels of DDE, although this association was not statistically significant (P = 0.16, Wilcoxon's test). There was no difference in polychlorinated biphenyl levels between the K-ras wild-type and mutant groups. Immunohistochemical staining for p53 protein did not differ by patient characteristics or clinical history, but significant associations were found with poor glandular differentiation (P = 0.002, chi2 trend test), severe nuclear atypia (P = 0.0007, chi2 trend test), and high tumor grade (P = 0.004, chi2 trend test). Our results are suggestive of the presence of K-ras codon 12 mutation-independent tumorigenesis pathways in patients with prior diabetes and possibly in patients with higher serum levels of DDE. Our results also support a role for the p53 tumor suppressor protein in the maintenance of genomic integrity.

Occupational exposure to p,p'-dichlorodiphenyltrichloroethane (DDT) has been associated with increased pancreatic cancer risk. We measured organochlorine levels in serum obtained at the study enrollment from 108 pancreatic cancer cases and 82 control subjects aged 32-85 years in the San Francisco Bay Area between 1996 and 1998. Cases were identified using rapid case-ascertainment methods; controls were frequency-matched to cases on age and sex via random digit dial and random sampling of Health Care Financing Administration lists. Serum organochlorine levels were adjusted for lipid content to account for variation in the lipid concentration in serum between subjects. Median concentrations of p,p'-dichlorodiphenyldichloroethylene (DDE, 1290 versus 1030 ng/g lipid; P = 0.05), polychlorinated biphenyls (PCBs; 330 versus 220 ng/g lipid; P0.001), and transnonachlor (54 versus 28 ng/g lipid; P = 0.03) were significantly greater among cases than controls. A significant dose-response relationship was observed for total PCBs (P for trend0.001). Subjects in the highest tertile of PCBs (or =360 ng/g lipid) had an odds ratio (OR) of 4.2 [95% confidence interval (CI) = 1.8-9.4] compared to the lowest tertile. The OR of 2.1 for the highest level of p,p'-DDE (95% CI = 0.9-4.7) diminished (OR = 1.1; 95% CI = 0.4-2.8) when PCBs were included in the model. Because pancreatic cancer is characterized by cachexia, the impact of this on the serum organochlorine levels in cases is difficult to predict. One plausible effect of cachexia is bioconcentration of organochlorines in the diminished lipid pool, which would lead to a bias away from the null. To explore this, a sensitivity analysis was performed assuming a 10-40% bioconcentration of organochlorines in case samples. The OR associated with PCBs remained elevated under conditions of up to 25% bioconcentration.

Epstein-Barr virus (EBV) associated lymphoproliferative disorders (LPD) similar to those that occur in immunosuppressed solid organ recipients have been reported in patients with rheumatoid arthritis (RA). These LPD cause significant morbidity and/or mortality in a state of sustained immunosuppression, but may spontaneously regress if immunocompetence is restored. We determined the population based frequency of EBV associated LPD relative to all non-Hodgkin's lymphomas (NHL) that occur in the general population of patients with RA.Forty-two case patients with NHL and RA and 49 control patients with NHL and no RA were identified in a population based, case control study of NHL that occurred in a 6 county Northern California area during the years 1988-94. The lymphoma tissue specimens were reviewed and the diagnosis of NHL was confirmed. In addition, the specimens were analyzed for NHL grade, histologic subtype, histopathologic features associated with immunosuppression, immunophenotype, and the presence of EBV genome in the tumor cells.No significant differences were identified between NHL in the RA case group and the control group (no RA) with respect to any variables investigated. One patient (2%) in the case group and one (2%) in the control group developed LPD containing EBV.Our findings reveal that EBV associated lymphomas represent only a small fraction of all NHL in the general RA patient population. EBV associated LPD should be recognized when they occur because they require a special approach to patient management. However, these data indicate that the majority of NHL that occurs in patients with RA is probably coincidental with RA and not the result of significant immunosuppression.

Nineteen counties from San Francisco and Los Angeles, California and Seattle, Washington were the United States sites for a large population-based case-control study of childhood brain tumors (CBTs), sponsored by the National Cancer Institute. CBT patients who were20 years of age and were diagnosed between 1984 and 1991 were reported to each region's cancer registry. The 801 control subjects were obtained by random digit dial and were frequency-matched to the 540 CBT patients in San Francisco and Seattle (one patient to two controls) and in Los Angeles (one patient to one control). Data collected by in-person interview with subjects' mothers were analyzed to investigate an association between risk for CBTs and life on a farm, exposure to farm animals (dairy cattle, beef cattle, pigs, sheep/goats, poultry, and horses), and some cat and non-farm horse exposures. Elevated risks for CBTs were observed in association with mothers' exposure to pigs [odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.2-12] and horses (OR = 2.2, 95% CI = 1.0-4.8) on a farm during the index pregnancy. Children diagnosed with primitive neuroectodermal tumors showed elevated risks for CBTs with personal and maternal prenatal exposure to pigs (child, OR = 4.0, 95% CI = 1.2-13; mother, OR = 11.9, 95% CI = 2.8-51) and poultry (child, OR = 3.0, 95% CI = 1.1-8.0; mother, OR = 4.0, 95% CI = 1.2-14). No other animal exposures of children or mothers were found to be consistently related to CBTs. Children diagnosed with primitive neuroectodermal tumors who were on a farm for1 year and were first on a farm when they were6 months of age also had increased risk for CBTs (OR = 3.9, 95% CI = 1.2-13). A somewhat increased risk for CBTs was found for children of mothers who ever had worked on livestock farms compared with mothers who never had worked on a farm (OR = 7.4, 95% CI = 0.86-64, based on five case mothers and one control mother who worked on livestock farms during the 5 years preceding the birth of the index child). The associations are consistent with those of two previous studies in Norway (P. Kristensen et al., Int. J. Cancer, 65: 39-50, 1996) and the United States and Canada (G. R. Bunin et al., Cancer Epidemiol. Biomark. Prev., 3: 197-204, 1994) that investigated the role of farm-related exposures in the etiology of CBTs.

To investigate the relationship of number and type of nevi to the development of melanoma.Case-control study.Outpatient clinics in referral hospitals.Cases were 716 consecutive patients with newly diagnosed melanoma identified at 2 melanoma centers between January 1, 1991, and December 31, 1992. Stratified random sampling of patients from outpatient clinics was used to identify 1014 participating controls of the same age, sex, race, and geographic distribution as the melanoma cases. All study subjects underwent an interview, a complete skin examination, photography of the most atypical nevi, and, if the patient was willing, a biopsy of the most atypical nevus.Number and type of nevi on the entire body were systematically reported. All diagnoses of clinically dysplastic nevi were confirmed by expert examiners.Risk for melanoma was strongly related to number of small nevi, large nondysplastic nevi, and clinically dysplastic nevi. In the absence of dysplastic nevi, increased numbers of small nevi were associated with an approximately 2-fold risk, and increased numbers of both small and large nondysplastic nevi were associated with a 4-fold risk. One clinically dysplastic nevus was associated with a 2-fold risk (95% confidence interval, 1.4-3.6), while 10 or more conferred a 12-fold increased risk (95% confidence interval, 4.4-31). Congenital nevi were not associated with increased risk of melanoma.Although nondysplastic nevi confer a small risk, clinically dysplastic nevi confer substantial risk for melanoma. On the basis of nevus number and type, clinicians can identify a population at high risk of this epidemic cancer for screening and intervention.

Cutaneous malignant melanoma occurs less frequently among non-White populations than among Whites. As a result, little is known about the incidence and epidemiology of melanoma among other race/ethnicity groups. Data from the California Cancer Registry (United States) among 879 Hispanic, 126 Asian, and 85 Black men and women diagnosed with melanoma in 1988-93 were analyzed and compared with data for 17,765 non-Hispanic White cases. Average, annual, age-adjusted incidence rates per 100,000 population were 17.2 for men (M) and 11.3 for women (W) for non-Hispanic Whites; 2.8 (M), 3.0 (W) for Hispanics; 0.9 (M), 0.8 (W) for Asians; and 1.0 (M), 0.7 (W) for non-Hispanic Blacks. Among men, melanoma occurred on the lower extremity for 20 percent of Hispanics, 36 percent of Asians, and 50 percent of Blacks compared with nine percent of non-Hispanic Whites, with similar but less pronounced differences in site distribution by race/ethnicity for women. Among men, melanoma was diagnosed after it had metastasized to a remote site for 15 percent of Hispanics, 13 percent of Asians, and 12 percent of Blacks, compared with six percent of non-Hispanic Whites. Among women, seven percent of Hispanics, 21 percent of Asians, and 19 percent of Blacks were diagnosed with late-stage melanoma compared with four percent of non-Hispanic Whites. Although histologic type was not specified for nearly half of the cases, Hispanic, Asian, and Black patients were more likely than non-Hispanic White patients to have been diagnosed with acral lentiginous melanoma. Melanoma among Hispanics, Asians, and Blacks differs in incidence, site distribution, stage at diagnosis, and histologic type from melanoma among non-Hispanic Whites, and identification of risk factors for melanoma in these race/ ethnicity groups would elucidate further the role of sun and other factors in the etiology of melanoma.

This study provides outcome data on the quality of life in 84 patients 40 years of age or older who had spinal reconstructive surgery. A 30-min questionnaire covering the patients' pre- and postoperative functional status, expectations for surgery, medication use, quality of life, and overall satisfaction was administered via telephone by a trained interviewer. Clinical data were obtained from chart and radiographic review. The majority of the patients had back or leg pain as their indication for surgery. Diagnoses included kyphosis, scoliosis, spinal stenosis, spondylolisthesis, and failed surgery. Overall satisfaction with functional status and surgical outcome was 81%, and there was significant improvement in most functional measures. This study suggests that improved qualify of life for the majority of appropriately selected spinal reconstruction patients is achievable in this mature population.

We evaluated the risk of brain tumor occurrence in relation to previous head injury in a population-based case-control study of 540 children with a primary brain tumor and 801 control children. The risk of a brain tumor among children with a previous head injury that resulted in medical attention was slightly elevated when compared with children with no reported head injury [odds ratio (OR) = 1.4; 95% confidence limits (CL) = 1.0, 1.9]. This effect was stronger when we restricted the head-injured group to the few children with loss of consciousness (OR = 1.6; 95% CL = 0.6, 3.9) or an overnight admission to a hospital (OR = 1.7; 95% CL 0.7, 4.6), relative to those with no head injury. We observed no appreciable association between brain tumor occurrence and birth injury involving the head or a forceps delivery. Among the few children with either a birth injury or forceps delivery and a subsequent head injury, we observed approximately twofold elevations in risk. The OR was 2.6 (95% CL = 1.1, 6.9) for those with a birth injury and subsequent head injury, relative to those with neither a birth injury nor head injury. Our results provide only weak evidence in support of head injury as an etiologic agent for brain tumor occurrence in children, although most of our exposed group had only mild head injury.

Brain tumors are the leading cause of death from childhood cancer, yet the causes of most of these tumors remain obscure. Few chemicals are effective in causing brain tumors experimentally after systemic administration of low doses; a notable exception is one group of N-nitroso compounds, the nitrosamides (in particular the nitrosoureas). Feeding pregnant animals nitrosamide precursors (e.g., sodium nitrite and an alkylamide such as ethylurea) causes a high incidence of nervous system tumors in offspring. This population-based epidemiological study was designed to test the hypothesis that maternal consumption during pregnancy of meats cured with sodium nitrite increases the risk of brain tumors among offspring. The intake of vitamins C and E blocks endogenous formation of nitroso compounds and was expected to be protective. Mothers of 540 children under age 20 with a primary brain tumor diagnosed during 1984-1991 and 801 control children in the same 19 counties on the U.S. West Coast were interviewed. Risk increased with increasing frequency of eating processed meats [odds ratio (OR) = 2.1 for eating at least twice a day compared to not eating; 95% confidence interval (CI) = 1.3-3.2; P = 0.003). Risk also increased with increasing average daily grams of cured meats or mg of nitrite from cured meats (P for each0.005) but not with nitrate from vegetables. Daily use of prenatal vitamins throughout the pregnancy decreased risk (OR = 0.54; CI = 0.39-0.75). Risk among mothers who consumed above the median level of nitrite from cured meat was greater if vitamins were not taken (OR = 2.4; CI = 1.4-3.6) than if they were (OR = 1.3). These effects were evident for each of three major histological types and across social classes, age groups, and geographic areas. This largest study to date of maternal diet and childhood brain tumors suggests that exposure during gestation to endogenously formed nitroso compounds may be associated with tumor occurrence. Laboratory exploration is needed to: (a) define dietary sources of exposure to alkylamides; (b) investigate the reactivity of nitrite in high concentration such as around bits of cured meats in the stomach after ingestion compared to nitrite in dilute solution; and (c) confirm that simultaneous ingestion of alkylamides and cured meats leads to the endogenous formation of nitrosamides.

Brain tumors are the second most common cancer in children after leukemia, yet the etiology of childhood brain tumors remains unknown. Tobacco smoke contains several dozen compounds that are known to be carcinogens. Among these are N-nitroso compound precursors, principally tobacco-specific nitrosamines. Although smoking has not been identified as a significant risk factor for the development of brain tumors in adults, fetuses and infants have incompletely formed blood-brain barriers that may allow the passage of carcinogenic tobacco metabolites into the central nervous system and initiate the formation of neural tumors. In this review, we present data from case-control and cohort studies published between 1971 and 1995 that examined the relationship between parental smoking during pregnancy and childhood brain tumors (CBTs). The majority of these studies found little association between CBTs and maternal smoking before or during pregnancy or between CBTs and maternal exposure to passive smoke during pregnancy.

An analysis of the relationship between the anatomic site of cutaneous melanoma, sun exposure, and phenotype was conducted in 355 women with histologically confirmed superficial-spreading melanoma and in 935 control subjects. The most frequent site for superficial-spreading melanoma was the leg. However, when major sun-related and phenotype risk factors were examined by site, risk ratios were lowest for melanomas that occurred on the leg. A history of frequent sunburns during elementary or high school, increased number of self-assessed large nevi, and blond hair were more strongly associated with melanoma sites other than the leg. Tumors on the trunk were more likely than tumors at other sites to be associated with histological evidence of a preexisting nevus. Results of this work indicate that associations between melanoma phenotypic factors may differ by anatomic site.

Using individual subject data from 10 case-control studies, comprising over 3000 cases and almost 4000 controls, we have estimated the relative risk of melanoma associated with aspects of complexion, namely, hair, eye and skin colour and freckling in adulthood, and have examined the relationships between these factors and naevus count in terms of melanoma risk. Compared with individuals with black or dark brown hair, the relative risks for developing melanoma in those with light brown, blonde and red hair were 1.49 (95% CI 1.31, 1.70), 1.84 (95% CI 1.54, 2.21) and 2.38 (95% CI 1.90, 2.97), respectively. Individuals with blue eyes had a risk 1.55 (95% CI 1.35, 1.78) times that for those with brown eyes, or 1.15 (95% CI 0.94, 1.40) after adjusting for hair colour and freckling in adulthood. The relative risks associated with hair and eye colour were independent of those for naevus count and skin colour. Light skin colour and high freckle density were also highly significant risk factors, independent of each other and of naevus count and hair and eye colour. The risks associated with these factors, while individually modest, are largely independent, and thus pigmentation characteristics and freckling tendency should be useful in identifying high risk groups to be targeted for prevention.

In a combined analysis of 2952 melanoma patients and 3618 controls from 8 case-control studies in white populations the risk of cutaneous melanoma was 2.24-fold higher (95% CI, 1.76-2.86) in subjects who reported at least one affected first-degree relative than in subjects who did not. There was no evidence for heterogeneity in the relative risk between the studies, which were from a wide range of latitudes and hence degrees of sun exposure. The effect of family history on melanoma risk was independent of age, naevus count, hair and eye colour, and freckling. There was no evidence for a relationship between family history and primary site of melanoma but there was some suggestion that the familial patients were more likely to have superficial spreading melanoma or lentigo maligna melanoma than acral lentiginous melanoma or nodular melanoma.

The recognition of dysplastic nevi from photographs can aid in population surveys of nevi and in epidemiological studies of melanoma risk. The reproducibility of techniques for recognizing nevi as dysplastic or for scoring them according to the degree of dysplasia has not been measured. Using photographs of 300 nevi taken in the course of a case-control study of melanoma, we assessed the agreement among six clinicians in independently categorizing nevi as dysplastic and in grading the degree of dysplasia. On average, reviewers agreed with each other 77% of the time in classifying a nevus as dysplastic or normal. Pairwise agreement within one point on a six-point scale occurred 87% of the time on average. These results suggest that criteria for recognizing nevi as clinically dysplastic from photographs can be applied reproducibility.

Factors related to menopause and use of exogenous hormones other than p.o. contraceptives were examined in 452 women ages 25-59 who were diagnosed with cutaneous malignant melanoma. Control subjects for this population-based study in the San Francisco Bay Area were 930 women of the same age. An increased risk was observed for superficial spreading melanoma (SSM) in women who reached natural menopause after age 55 [odds ratio (OR), 3.6; 95% confidence interval (CI), 1.1-11.1], and for women who had had a bilateral oophorectomy within 9 years of their diagnosis with SSM (OR, 2.2; CI, 1.1-4.5). A somewhat elevated risk of melanoma after natural menopause or hysterectomy was no longer statistically significant after adjustment for exogenous hormone use. Prolonged use of p.o. exogenous hormones after hysterectomy for women who had retained at least one ovary was associated with an increased risk of SSM (OR, 5.4; CI, 1.5-19.3), and use of these products for fewer than 5 years after bilateral oophorectomy also was associated with an elevated risk of SSM (OR, 2.9; CI, 1.0-7.8). Conjugated estrogen use was associated with somewhat elevated risks for SSM after hysterectomy with one ovary retained (OR, 2.7; CI, 0.97-7.3) and after hysterectomy with bilateral oophorectomy (OR, 2.1; CI, 0.86-5.0). There was a suggestion of a trend for increased risk of SSM with increased dosage of conjugated estrogens after hysterectomy (P for trend = 0.07). Use of vaginal creams that contained estrogen also was associated with an increased risk of SSM (OR, 1.8; CI, 1.0-3.3).

The Salmonella mutagenicity test was used to analyze cervical mucus specimens from 364 smokers and 333 nonsmokers to determine whether the association between smoking and mutagenic cervical mucus that we reported previously among women diagnosed with dysplasia would apply to a larger group of healthy women (E. A. Holly et al., J. Natl. Cancer Inst., 76: 983-986, 1986). Women smokers and nonsmokers between the ages of 18 and 49 who attended eleven clinics and physicians' offices in the San Francisco Bay area for a routine Pap smear were examined to determine whether smokers were more likely to have mutagenic substances in their cervical mucus. About 4% of smokers and 8% of nonsmokers had positive mutagenicity test results (P = 0.02). Cervical mucus with a large number of microorganisms was more likely to have a positive mutagenicity test result than that with fewer microorganisms (test for trend, P = 0.01). Mutagenicity results varied by race and clinic location but were not associated with smoking behavior, sexual behavior, gynecological diagnosis, or diet. Further work is needed to develop methods to detect mutagens in specific body fluids.

Previous studies have demonstrated a high prevalence of anal cytologic abnormalities as well as anal human papillomavirus (HPV) infection among homosexual men with group IV HIV disease. However, the natural history of these changes in this population has not yet been studied. To this end, 37 homosexual men with group IV HIV disease attending an outpatient HIV clinic were followed at approximately 9-month intervals for an average of 17 months, using anal cytology, anoscopy, anal biopsy, and anal HPV DNA hybridization. During the study, the proportion of the 37 subjects with anal cytologic abnormalities increased from 27 to 65%. The proportion of subjects with any grade of anal intraepithelial neoplasia rose from 8 to 32%, with high-grade anal intraepithelial neoplasia increasing from 0 to 16%. The proportion of subjects with anal HPV infection increased from 60 to 89%, and infection with multiple HPV types was noted in at least 48%. We conclude that a large proportion of homosexual men with group IV HIV disease develop anal cytologic abnormalities, including anal intraepithelial neoplasia, over a short period of time. Together with a rapidly increasing incidence of anal cancer among single, never-married men in the San Francisco Bay area, these results suggest that these men may be at significant risk of development of anal cancer.

To better understand why smokers are more likely to develop cervical cancer than nonsmokers, we investigated laboratory and demographic differences between the two groups. Women between the ages of 18 and 49 who attended eleven community clinics in the San Francisco Bay Area were studied to investigate differences between smokers and nonsmokers. The 332 smokers and 365 nonsmokers were queried about smoking habits, sexual and reproductive history, and recent diet. Cervical mucus specimens were cultured for yeast, lactobacillus, and other microorganisms. Results showed that white Hispanic women were less likely to smoke than white non-Hispanic women. Smokers, when compared to nonsmokers, consumed larger quantities of coffee, soft drinks, liquor, and beer in the 24 h prior to the interview. Women who smoked were more likely than those who did not smoke to have had first sexual intercourse before age 16, had a greater number of lifetime sexual partners, and were more likely than nonsmokers to have been pregnant. After controlling for number of sexual partners, smokers reported a history of chlamydia, gonorrhea, and/or pelvic inflammatory disease more often than did nonsmokers, and cervical mucus of smokers was more likely than that from nonsmokers to contain greater than 8500 microorganisms/ml.

A stepwise logistic regression analysis was employed to evaluate the usefulness of the following criteria to distinguish adenocarcinoma in pleural effusion from benign pleural effusion: increased size of nucleus, increased nuclear to cytoplasmic ratio, irregular nuclear borders, sharply defined cytoplasmic boundaries, large nucleoli, aggregates with variable size nuclei, aggregates with nuclear overlap, irregular noncentral vacuoles, aggregates with nuclear molding, multinucleation, three-dimensional aggregates, aggregates with large cytoplasmic vacuoles, atypical mitoses, nuclear vacuoles, homogeneous cytoplasm, aggregates with associated lymphocytes and neutrophils, and uniform size aggregates. A total of 223 patients with benign pleural effusion cases and 221 patients with adenocarcinoma in their pleural effusion were scored as to the presence or absence of the above criteria. The resulting data were subjected to a stepwise logistic regression analysis that chose increased nuclear/cytoplasmic ratio, irregular nuclear borders, large nucleoli, sharply defined cytoplasmic boundaries, and three-dimensional aggregates as the best criteria to differentiate adenocarcinoma in pleural effusion from benign pleural effusion. When used together, these five features had a sensitivity of 94% and a specificity of 93% for predicting adenocarcinoma.

Forty anal paraffin-embedded tissue specimens from 24 subjects were studied for the presence of human papillomavirus (HPV) types 6, 11, 16, 18, 31, and 33, herpes simplex virus (HSV), Epstein-Barr virus, and cytomegalovirus DNA by using the polymerase chain reaction. These tissues ranged from histologically normal to invasive squamous cell carcinoma. HPV DNA was detected in the invasive anal cancer tissues of 11 of 13 subjects. HPV types were segregated by histopathological severity, with HPV 16 associated exclusively with high grade anal intraepithelial neoplasia and invasive cancer. HPV types 6 and 11 were associated with condyloma and low grade anal intraepithelial neoplasia. HPV DNA in situ hybridization studies confirmed the presence of HPV DNA in the invasive cancer tissues of 6 of 12 subjects. HPV DNA in these tissues was highly focal and primarily associated with invasive cell nests that demonstrated the greatest degree of squamous differentiation. HSV DNA was detected only in association with advanced disease, being found in the cancer tissues of 5 of 13 subjects, and in 3 of 4 subjects with high grade anal intraepithelial neoplasia, but was not detected by in situ hybridization. Epstein-Barr virus and cytomegalovirus DNA were not detected in the 40 tissue specimens. We conclude that HPV infection may play an important role in the pathogenesis of anal cancer. The association between HSV infection and high grade anal disease suggests that HSV infection may also play a role in disease progression.

We conducted a case-control interview study among 1277 subjects (407 patients, 870 controls selected by using random digit dial) in 11 western United States to determine whether uveal melanoma and cutaneous melanoma shared common risk factors. After adjustment for other factors, the risk of uveal melanoma was increased for those with green, gray, or hazel eyes [relative risk (RR) = 2.5, P less than 0.001] or blue eyes (RR = 2.2, P less than 0.001) when compared to brown. A tendency to sunburn after 0.5 h midday summer sun exposure increased risk for uveal melanoma (burn with tanning RR = 1.5, P = 0.02; burn with little tanning RR = 1.8, P less than 0.001; burn with no tanning RR = 1.7, P = 0.002); as did exposure to UV or black lights (RR = 3.7, P = 0.003); and welding burn, sunburn of the eye, or snow blindness (RR = 7.2, P less than 0.001). An association with uveal melanoma was also noted with an increasing number of large nevi (P = 0.04 for trend), although the individual risk estimates were not remarkable. These data suggest that host factors and exposure to UV light are risk factors for uveal melanoma.

Fine needle aspiration (FNA) biopsy is an increasingly popular method for the evaluation of salivary gland tumors. Of the common salivary gland tumors, mucoepidermoid carcinoma is probably the most difficult to diagnose accurately by this means. A series of 96 FNA biopsy specimens of salivary gland masses, including 34 mucoepidermoid carcinomas, 51 other benign and malignant neoplasms, 7 nonneoplastic lesions and 4 normal salivary glands, were analyzed in order to identify the most useful criteria for diagnosing mucoepidermoid carcinoma. Thirteen cytologic criteria were evaluated in the FNA specimens, and a stepwise logistic regression analysis was performed. The three cytologic features selected as most predictive of mucoepidermoid carcinoma were intermediate cells, squamous cells and overlapping epithelial groups. Using these three features together, the sensitivity and specificity of accurately diagnosing mucoepidermoid carcinoma were 97% and 100%, respectively.