Showing papers in "Cancer Epidemiology, Biomarkers & Prevention in 1993"

Vitamin D and prostate cancer: a prediagnostic study with stored sera.

Abstract: This study evaluates the risk of prostate cancer in relation to serum levels of the major vitamin D metabolites, 25-hydroxyvitamin D (25-D3) and 1,25-dihydroxyvitamin D (1,25-D). Between 1964 and 1971, more than 250,000 serum samples were collected from members of the Kaiser Permanente Medical Care Plan in Oakland and San Francisco and stored for future use. Levels of 25-D and 1,25-D were measured in samples from 90 black and 91 white men diagnosed with prostate cancer before December 31, 1987 and controls individually matched on age, race, and day of serum storage. Mean serum 1,25-D was 1.81 pg/ml lower in cases than in matched controls (P = 0.002). Risk of prostate cancer decreased with higher levels of 1,25-D especially in men with low levels of 25-D. However, mean 25-D was not significantly different in cases and controls. The association of lower 1,25-D with prostate cancer was found in men above the median age of 57 years at serum storage but not younger men and was similar in black and white men. In men > or = 57 years of age, 1,25-D was an important predictor of risk for palpable and anaplastic tumors but not for tumors incidentally discovered during surgery to treat the symptoms of benign prostatic hyperplasia or well differentiated tumors.

Predictors of long-term smoking cessation in head and neck cancer patients.

Abstract: Cigarette smoking is a major risk factor for head and neck cancer, and individuals who continue to smoke past diagnosis and treatment are at elevated risk for further disease. In a randomized controlled trial, a state of the art provider-delivered smoking cessation intervention was compared to a usual care advice control condition. The intervention consisted of surgeon- or dentist-delivered advice to stop smoking, a contracted quit date, tailored written materials, and booster advice sessions. Subjects were 186 patients with newly diagnosed first primary squamous cell carcinomas of the upper aerodigestive tract who had smoked cigarettes within the past year. At randomization, 88.2% of subjects were current smokers. At 12-month follow-up, 70.2% of subjects completing the trial (n = 114) were continuous abstainers; among baseline smokers alone the continuous abstinence (CA) rate was 64.6%. The cotinine validation rate at 12 months was 89.6%. Modeling techniques were utilized in order to derive expected CA rates, which included noncompleter subjects (n = 72). The CA rate expected at 1 year for the entire patient population was 64.2%, and for smokers alone the expected CA rate was 59.4%. Logistic regression analysis carried out on baseline smokers identified predictors of 12-month CA status. These included medical treatment, stage of change, age, nicotine dependence, and race. The intervention effect was not significant, although the sign of the effect was positive. Based on these findings, we recommend systematic brief advice to stop smoking for head and neck cancer patients, with a stepped care approach for patients less able to quit.

Toenail trace element levels as biomarkers: reproducibility over a 6-year period.

Abstract: We assessed the reproducibility over a 6-year period of 16 trace elements measured in toenails by comparing levels in paired specimens collected in 1982-1983 and 1988 from 127 women in the United States. The Spearman correlation coefficients for the reproducibility of toenail levels of selenium and arsenic (both known to reflect intake of these elements) were 0.48 and 0.54. Correlations for other elements ranged from 0.26 (copper) to 0.58 (zinc). In utilizing biomarkers to assess exposure in epidemiological studies of cancer and other chronic disease, random within-person variability in exposure leads to attenuation of measures of association between exposure and disease. We demonstrate the effect of such variability on odds ratios from a hypothetical case-control study. For a true odds ratio of 3.0 (for a comparison of the highest quintile versus the remaining 4 quintiles of exposure) the odds ratios which would be observed in the presence of the degree of within-person variability demonstrated in this study were 2.15 for toenail arsenic and 1.67 for toenail copper levels. Toenail concentrations of certain trace elements are useful biomarkers of exposure in which a single sample is assumed to represent long-term exposure. However, substantial attenuation in measures of association may occur.

Intake of specific carotenoids and lung cancer risk.

Abstract: Using newly available food composition data for carotenoids, the authors reanalyzed a population-based case-control study of diet and lung cancer conducted in Hawaii in 1983-1985 (L. Le Marchand et al., J. Natl. Cancer Inst., 81: 1158-1164, 1989). The analysis included interviews with 230 men and 102 women with lung cancer and 597 men and 268 women as controls, frequency-matched to the patients by age and sex. A previously validated quantitative diet history assessed the usual intake of foods rich in carotenoids. After adjusting for smoking and other covariates, no association was found with lung cancer risk for dietary lycopene or beta-cryptoxanthin intake, whereas dose-dependent inverse associations of comparable magnitude were found for dietary beta-carotene, alpha-carotene, and lutein. When subjects were cross-classified by their joint intakes of the latter three carotenoids, those who had a high intake (> median) for all three had the lowest risk for lung cancer. In a similar two-way interaction analysis, the previously reported inverse association of lung cancer with vegetable consumption in these data was found to be stronger than that with intake of these three carotenoids. Consistent with our previous findings, this analysis provides further evidence for a protective effect of certain carotenoids against lung cancer and for the greater protection afforded by consuming a variety of vegetables compared to only foods rich in a particular carotenoid.

Cholangiocarcinoma: epidemiology, mechanisms of carcinogenesis and prevention.

Abstract: Cholangiocarcinoma is a relatively rare cancer; worldwide it accounts for an estimated 15% of liver cancers. In most areas, the etiology is rather obscure, and identified risk factors such as hepatolithiasis, inflammatory bowel disease, and exposure to Thorotrast can account for only a small proportion of cases. In certain areas of southeast and eastern Asia, however, incidence rates are very high, and here there is a strong association with infection with the liver flukes Clonorchis sinensis and Opisthorchis viverrini. The mechanisms of carcinogenesis in O. viverrini infection have been the subject of considerable research; it seems that the presence of parasites induces DNA damage and mutations as a consequence of the formation of carcinogens/free radicals and of cellular proliferation of the intrahepatic bile duct epithelium. Preventive strategies in areas endemic for liver flukes appear straightforward, but breaking the cycle of infection has proved difficult in practice.

Epidemiology of colorectal adenomatous polyps.

Abstract: 7% of Americans are expected to develop this disease within their lifetime (2). Efforts to identify causes and effective preventive measures for this disease have led to the hypothesis that adenomatous polyps (adenomas), benign tumors that arise in the large bowel, are precursor lesions for the vast majority of colorectal cancers (3).

Relation of endometrial cancer risk to past and contemporary body size and body fat distribution.

Abstract: In a multicenter case-control study that included 403 cases and 297 controls, we examined the relation of past and contemporary body size, including body fat distribution, to the risk of endometrial cancer. The relative contributions of past and contemporary body size were assessed by examining weight and height histories provided by the subjects. Anthropometric indicators thought to reflect early environmental influences (e.g., height and sitting height), current weight, and fat distribution patterns were measured directly. Height was not a risk factor for endometrial cancer, but inexplicably, sitting height was inversely associated with risk. Weight during early adulthood appeared to be directly related to disease risk, but the association was explained by contemporary weight and thus weight gain during adulthood. While contemporary weight was associated with risk of endometrial cancer, the effect was restricted to those in the top quartile. Women whose measured weight at interview exceeded 78 kg had 2.3 times the risk of those weighing less than 58 kg (95% confidence interval, 1.4 to 3.7). Upper-body obesity (waist-to-thigh circumference ratio) was a risk factor independent of body weight. After adjustment for weight, the relative risks of endometrial cancer across increasing quartiles of upper-body obesity were 1.0, 1.5, 1.8, and 2.6 (P for trend < 0.001). These data indicate that both obesity and the distribution of adipose tissue accumulated during adult life increase endometrial cancer risk substantially.

Serological precursors of cancer: serum hormones and risk of subsequent prostate cancer.

Abstract: A population-based nested case-control study was conducted to determine the relation of prediagnostic serum levels of testosterone, dihydrotestosterone, prolactin, follicle-stimulating hormone, luteinizing hormone, estrone, and estradiol to the risk of subsequent prostate cancer. Serum specimens of study subjects were available from a blood collection campaign in Washington County, Maryland, in 1974. Serum hormone levels of 98 histologically confirmed prostate cancer cases diagnosed in the subsequent 13 years were compared to those of 98 controls who were individually matched to cases on the basis of age (within weeks), sex, and race. There were no significant differences in levels of these hormones between cases and controls, although elevated levels of luteinizing hormone and of testosterone:dihydrotestosterone ratios were associated with mild increased risks of prostate cancer.

Attributable risk for oral cancer in northern Italy

Abstract: Using data from a case-control study conducted between 1984 and 1992 in the provinces of Milan and Pordenone, northern Italy, on 439 cases of oral and pharyngeal cancers and 2106 hospital controls, we computed the population attributable risk for oropharyngeal cancer in relation to tobacco, alcohol, and a measure of low beta-carotene intake. Two different models were used for estimating relative risks, one assuming that the three factors act multiplicatively on the relative risk and the second estimating separately each combination of alcohol and tobacco and assuming a multiplicative model only for beta-carotene. The estimated attributable risks were similar for the two models considered. For both models and both sexes, the single factor with the highest attributable risk was smoking, which accounted for 81-87% of oral cancers in males and for 42-47% in females. Alcohol explained about 60% of male cases, but only 15% of female ones, and low beta-carotene accounted for 24% of total cases (25% of males, 17% of females). Together the three factors were responsible for 91-94% of oropharyngeal cancers in males, 51-57% in females, and 85-88% in both sexes combined. The present knowledge of major identified risk factors could, in principle, reduce the burden of the disease in Italy from 2400 to about 200 deaths per year for males and from 500 to 230 for females, thus explaining the difference in incidence and mortality between the two sexes.

Cytogenetic effects of formaldehyde exposure in students of mortuary science.

Abstract: The effect of low-level exposure to formaldehyde on oral, nasal, and lymphoycte biological markers was studied prospectively in a group of 29 mortician students who were about to take a course in embalming. During the 85-day study period, the subjects performed an average of 6.9 embalmings and had average cumulative formaldehyde exposures of 14.8 ppm-h, with an average air concentration of 1.4 ppm during embalming. Since the average time spent embalming was 125 min, formaldehyde exposures calculated as an 8-h time-weighted average were 0.33 ppm on days when embalmings were done, which was less than the Occupational Safety and Health Administration permissible exposure limit of 0.75 ppm. Epithelial cells from the buccal area of the mouth showed a 12-fold increase in micronucleus frequency during the study period, from 0.046 +/- 0.17/1000 cells preexposure to 0.60 +/- 1.27/1000 cells at the end of the course (P < 0.05). Nasal epithelial micronuclei increased 22%, from 0.41 +/- 0.52/1000 cells to 0.50 +/- 0.67/1000 cells (P = 0.26). In blood cells, the frequency of micronucleated lymphocytes increased 28%, from 4.95 +/- 1.72/1000 cells to 6.36 +/- 2.03/1000 cells (P < 0.05), while sister chromatid exchanges decreased 7.5% (P < 0.05). A dose-response relationship was observed between cumulative exposure to formaldehyde and increases in buccal micronuclei in the 22 male subjects but not in the 7 female subjects. We conclude that low-level exposure to formaldehyde is associated with cytogenetic changes in epithelial cells of the mouth and in blood lymphocytes. These cytogenetic effects may be useful as markers of biologically effective dose.

Human papillomavirus and cervical intraepithelial neoplasia grade III/carcinoma in situ: a case-control study in Spain and Colombia.

Abstract: A case-control study of 525 cases of cervical intraepithelial neoplasia grade III (CIN III) and 512 controls was conducted in Spain and Colombia between 1985 and 1988 to assess the role of human papillomavirus (HPV) in the etiology of CIN III. HPV DNA in cytological scrapes from the cervix was assessed by Virapap and by polymerase chain reaction (PCR) based on the L1 consensus primers. A subsample of 268 specimens was also tested for HPV DNA using Southern hybridization. In Spain, the PCR-based prevalences of HPV DNA were 70.7% among cases and 4.7% among controls. Odds ratio (OR) and 95% confidence interval (numbers in parentheses) for HPV DNA were 56.9 (24.8-130.6). In Columbia HPV DNA was detected by PCR in 63.2% of the cases and in 10.5% of the controls. The OR was 15.5 (8.2-29.4). The estimated fractions of CIN III attributable to HPV were 72.4% in Spain and 60.3% in Colombia. HPV 16 was the predominant viral type and showed the strongest association with CIN III; in Spain the OR was 295.5 (44.8-1946.4) and in Colombia the OR was 27.1 (10.6-69.5). HPV DNA of unknown type was frequent in HPV-positive cases (18.3% in Spain and 38.0% in Colombia) and controls (66.7% in Spain and 47.4% in Colombia). The comparison of results from Virapap and PCR indicated that PCR is the method of choice for epidemiological studies. These data strongly support the hypothesis of the viral origin of CIN III, the common etiology of CIN III and invasive cervical cancer, and the causal nature of the association between HPV and CIN III.

Lung cancer, race, and a CYP1A1 genetic polymorphism.

Abstract: The assessment of human cancer risk using molecular epidemiological techniques involves determining the relative contributions of inherited and acquired genetic predispositions, in the context of environmental exposures. Recently described genetic polymorphisms for CYP1A1, a gene involved in the metabolic activation of polycyclic aromatic hydrocarbons, have been associated with lung cancer risk in a Japanese population. We report herein findings from a United States case-control study of lung cancer (56 cases; 48 controls). The polymerase chain reaction followed by an Msp1 restriction enzyme digestion was used to analyze constitutive DNA but no association between the restriction fragment length polymorphism and lung cancer risk was found (odds ratio, 0.7; 95% confidence interval, = 0.3-1.6). Analysis of genotype by cumulative smoking status did not reveal an elevated risk among lesser or greater smokers. The presence of the CYP1A1 Msp1 site-present allele, which was previously found to be associated with Japanese lung cancer risk, was statistically increased in African compared to Caucasian Americans (odds ratio, 2.9; 95% confidence interval, 1.2-2.7). When stratified by race, however, no association between case status and the polymorphism was observed, but the small number of study subjects within each racial group limited the statistical power. Larger studies are required to evaluate the risk of the CYP1A1 Msp1 polymorphism in African Americans.

Risk factors for cervical intraepithelial neoplasia grade III/carcinoma in situ in Spain and Colombia.

Abstract: A case-control study of 525 histologically confirmed cases of cervical intraepithelial neoplasia grade III and 512 controls was done in Spain and Colombia to assess the role of various risk factors taking into account the effect of human papillomavirus (HPV). The presence of HPV DNA, assessed by a polymerase chain reaction-based method, was the strongest risk factor identified. In Spain the adjusted odds ratio (OR) and 95% confidence interval (CI) (numbers in parentheses) were 56.9 (24.8-130.6) and, in Colombia, were 15.5 (8.2-29.4). In addition to HPV, the multivariate analysis revealed independent effects of early age at first intercourse (in Spain ORa, 4.3; 95% CI, 2.0-9.3 for ages or = 6 versus 1) while number of partners of the woman and specially of her husband showed a strong effect in Spain only (ORa, 6.9; 95% CI, 3.1-15.3 for partners of the husband > or = 21 versus 1-5). Smoking and use of oral contraceptives did not show significant or consistent associations. Among HPV-DNA positive women early age at first intercourse and high parity increased the risk of cervical intraepithelial neoplasia III but the effect was statistically significant only for the former.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum micronutrients and the subsequent risk of cervical cancer in a population-based nested case-control study.

Abstract: A nested case-control study was conducted in Washington County, MD, to determine whether low serum micronutrients are related to the subsequent risk of cervical cancer. Among the 15,161 women who donated blood for future cancer research during a serum collection campaign in 1974, 18 developed invasive cervical cancer and 32 developed carcinoma in situ during the period January 1975 through May 1990. For each of these 50 cases, two matched controls were selected from the same cohort. The frozen sera of the cases and their matched controls were analyzed for a number of nutrients. The mean serum levels of total carotenoids, alpha-carotene, beta-carotene, cryptoxanthin, and lycopene were lower among cases than they were among controls. When examined by tertiles, the risk of cervical cancer was significantly higher among women in the lower tertiles of total carotenoids (odds ratio 2.7; 95% confidence limit, 1.1-6.4), alpha-carotene (odds ratio, 3.1; 95% confidence limit, 1.3-7.6), and beta-carotene (odds ratio, 3.1; 95% confidence limit, 1.2-8.1) as compared to women in the upper tertiles and the trends were statistically significant. Cryptoxanthin was significantly associated with a lower risk of cervical cancer when examined as a continuous variable. Retinol, lutein, alpha- and gamma-tocopherol, and selenium were not related to cervical cancer risk. Smoking was also strongly associated with cervical cancer. These findings are suggestive of a protective role for total carotenoids, alpha-carotene and beta-carotene in cervical carcinogenesis and possibly for cryptoxanthin and lycopene as well.

Mutagen sensitivity in upper aerodigestive tract cancer: a case-control analysis.

Abstract: Variability in DNA repair capability may be a determinant of interindividual difference in susceptibility to carcinogenic exposures. A cytogenetic assay which quantifies chromosomal breakage induced by in vitro exposure to a clastogen provides an indirect measure of repair. We report the results of a case-control study of upper aerodigestive tract cancers assessing differences in mutagen sensitivity based on this assay. There were 108 cases with previously untreated squamous cell cancers and 108 age and sex frequency-matched controls selected from blood donors to The University of Texas M. D. Anderson Cancer Center. Sixty-nine% of the cases, compared with 44% of the controls, were classified as mutagen sensitive (breaks per cell > or = 0.8). On multivariate analysis, mutagen sensitivity [odds ratio (OR), 2.5], heavy cigarette smoking (OR, 4.8), and heavy alcohol consumption (OR, 3.1) were associated with significantly increased risk. Stratified analyses showed that the combined effects of cigarette smoking (OR, 8.1) and mutagen sensitivity (OR, 3.2) were suggestive of a multiplicative effect (OR, 23.0). The combined estimate for alcohol use (OR, 3.0) and mutagen sensitivity (OR, 3.0) was 5.8. These data confirm those of a previously published preliminary study of upper aerodigestive cancers and underscore the importance of considering interindividual susceptibility in cancer risk characterization, even for those cancers with well quantified exposures.

Cigarette smoking and alcohol consumption by parents of children with acute myeloid leukemia: an analysis within morphological subgroups--a report from the Childrens Cancer Group.

Abstract: Data from a case-control study of childhood acute myeloid leukemia (AML) including 187 matched case-control pairs were examined for evidence of associations between parental cigarette smoking and alcohol consumption and the subsequent development of childhood AML. The cases were stratified by French-American-British morphology in order to evaluate potential differences in risk based on this classification system. There was little evidence of any association between cigarette smoking by parents during the index pregnancy and childhood AML. There was some evidence of an increased risk of AML among children who were diagnosed at or before 2 years of age and whose mothers reported consuming alcohol during their pregnancies (odds ratio, 3.00; 95% confidence interval, 1.23 to 8.35). This finding appeared to be especially pronounced for AML with a monocytic component (M4/M5) (odds ratio, 9.00; 95% confidence interval, 1.25 to 394.5), but a cautious interpretation of these data are advised because of the small number of subjects included in this subgroup analysis. Since this is one of the first case-control studies to evaluate specific French-American-British subtypes of AML, these results may be viewed as generating hypotheses. It is suggested that future studies of childhood AML include: (a) a sufficient number of cases to permit an evaluation of the morphological classification of the cases; and (b) additional questions on the alcohol consumption of the mother during the time of her pregnancy with the index child.

Dietary intake as a risk factor for cancer of the exocrine pancreas.

Abstract: Data from 149 cases with pancreatic cancer and 363 control subjects in Utah were obtained from proxy respondents to assess the associations between dietary intake and the development of pancreatic cancer. After adjusting for cigarette smoking status and alcohol and coffee consumption, we observed that foods containing large amounts of fat from all sources increased risk of pancreatic cancer in men [odds ratio (OR), 3.41; 95% CI, 1.59-7.29]. Further division of fat by source of food showed that high intake of bacon and sausages (OR for upper tertile, 2.77; 95% CI, 1.34-5.72) as well as large intakes of fatty foods other than meat or dairy products (OR for upper tertile, 2.80; 95% CI, 1.33-5.89) increased risk of pancreatic cancer in men; high levels of intake of red meat, chicken, fish, and dairy foods did not increase risk of pancreatic cancer in either men or women. In women, fat from nonmeat and nondairy sources also increased risk of pancreatic cancer (OR for upper tertile, 3.44; 95% CI, 1.35-8.78). Although no protective effect was observed among men who consumed large amounts of fruits, vegetables, or high fiber foods, we did observe a protective effect in women for these foods (OR for upper tertile of fruit consumption, 0.37; 95% CI, 0.18-0.81; OR for upper tertile of vegetable consumption, 0.32; 95% CI, 0.13-0.74; and OR for upper tertile of fiber consumption, 0.28; 95% CI, 0.12-0.67). Findings from this study support the hypothesis that diets high in fat contribute to the development of pancreatic cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma selenium concentration predicts the prevalence of colorectal adenomatous polyps

Abstract: The objective of this cross-sectional study was to determine whether plasma selenium concentration predicts the prevalence of adenomatous polyps of the colon and rectum. The source population for the study was 101 patients undergoing sequential colonoscopies at the Veterans Affairs Medical Center, Tucson, AZ. The study population was then limited to the 48 patients (all male) undergoing their initial colonoscopy who did not have a diagnosis of colorectal cancer. For each of these patients, a prediagnostic fasting plasma selenium concentration was determined. The data from this study suggest that fasting plasma selenium concentrations may be an important risk factor for colorectal adenomas. Patients with fasting plasma selenium concentrations below the median (< 128 mcg/liter) were significantly more likely to have one or more adenomatous polyps (prevalence odds ratio 4.2) and more adenomatous polyps (3.5 times) per patient. There was also a suggestion of a more proximal distribution of adenomatous polyps in the patients with a lower level of selenium. These associations were not confounded by age or smoking. The results of this study are consistent with the experimental animal studies, geographic mortality studies, and prospective cohort studies of selenium and colorectal cancer.

The association between cancers of the small and large bowel.

Abstract: Malignant tumors of the small bowel are rare and little is known about their etiology, although adenocarcinomas share certain epidemiological features with colorectal cancer. This study investigated what cancers, if any, occurred as second neoplasms following adenocarcinomas, malignant carcinoid tumors, lymphomas, and sarcomas of the small bowel. For all 2581 cases of small bowel malignancy registered in one of the Surveillance, Epidemiology, and End-Results program areas, 1973-1988, the relative risk of a second malignancy was determined. The risk of colorectal cancer was increased following adenocarcinoma of the small bowel, and the risk of adenocarcinoma of the small bowel was increased following colorectal cancer in both males and females. This study also found an association between small bowel sarcomas and malignant melanoma in males, consistent with earlier studies, and an association between prostate cancer and malignant carcinoid tumors of the small bowel, a new observation. We conclude that adenocarcinomas of the small bowel may share risk factors with colorectal cancer.

Aflatoxin, liver enzymes, and hepatitis B virus infection in Gambian children.

Abstract: The relative contribution of, and possible mechanism of interaction between, aflatoxin and hepatitis B virus (HBV) in the development of primary hepatocellular carcinoma can be better investigated now that markers of individual exposure to both factors are available. In this study, blood samples were collected over a 1-month period from 117 children aged 3 to 4 years, resident in Kuntair or Kerr Cherno in the Upper Niumi District of The Gambia. Samples were analyzed for aflatoxin-albumin (AF-alb) adducts, markers of HBV infection, liver enzymes [serum alanine aminotransferase (ALT)] as markers of liver damage, and glutathione S-transferase M1 genotype. All but two children showed detectable serum AF-alb with levels ranging from 2.2 to 250.4 pg aflatoxin B1-lysine equivalent/mg albumin. There was a significant positive correlation between AF-alb and ALT (r = 0.4; P < 0.001). HBV carriers showed moderately higher levels of AF-alb than noncarriers but the difference was not statistically significant and the association between AF-alb and ALT was unchanged when the HBV carriers were excluded from the analysis, suggesting that factors other than HBV infection contributed to the association. The null glutathione S-transferase M1 genotype was infrequent (17.7%) in this population and was not associated with any difference in AF-alb adduct levels compared to glutathione S-transferase M1-positive individuals. However, the percentage of individuals with the null genotype varied significantly between ethnic groups with 32.1% in Fula, 8.8% in Mandinka, and 13.3% in Wollof.(ABSTRACT TRUNCATED AT 250 WORDS)

Familial Barrett esophagus and adenocarcinoma of the gastroesophageal junction.

Abstract: Barrett esophagus was found in seven members of a single family. Two of these patients also had adenocarcinoma of the gastroesophageal junction. Among family members who did not have Barrett epithelium, one had esophageal ulcerations with dysplasia in squamous epithelium and another had an esophageal stricture. The pattern of involvement suggests autosomal dominant inheritance of Barrett esophagus and/or gastroesophageal reflux disease in this family, with a strong predisposition for adenocarcinoma of the esophagus.

Contribution of occupation and diet to white blood cell polycyclic aromatic hydrocarbon-DNA adducts in wildland firefighters.

Abstract: Wildland (forest) firefighters are exposed to a wide range of carcinogenic polycyclic aromatic hydrocarbons (PAH) in forest fire smoke. PAH undergo metabolic activation and can subsequently bind to DNA. In this study, we investigated the association between occupational and dietary PAH exposures and the formation of WBC PAH-DNA adducts in a population of wildland firefighters. An enzyme-linked immunosorbent assay using an antiserum elicited against benzo(a)pyrene-modified DNA was used to measure PAH-DNA adducts in WBC obtained from 47 California firefighters at two time points, early and late in the 1988 forest fire season. PAH-DNA adduct levels were not associated with cumulative hours of recent firefighting activity. However, firefighters who consumed charbroiled food within the previous week had elevated PAH-DNA adduct levels, which were related to frequency of charbroiled food intake. These findings suggest that dietary sources of PAH contribute to PAH-DNA adduct levels in peripheral WBC and should be evaluated when using this assay to assess occupational and environmental PAH exposure.

The Carotene and Retinol Efficacy Trial (CARET) to prevent lung cancer in high-risk populations: pilot study with cigarette smokers.

Abstract: In preparation for a phase IV lung cancer chemoprevention trial, we conducted a pilot trial of beta-carotene and retinol in high-risk smokers. Eligibility criteria were ages of 50-69 years, a smoking history of at least 20 pack-years, and either being a current smoker or having quit within the past 6 years. Participants were recruited by mailing an interest survey to 29,928 age-selected members of King County Medical Blue Shield. We randomized 1,029 women and men to one of four intervention arms: placebo, retinol, 25,000 international units/day; beta-carotene, 30 mg/day; or retinol plus beta-carotene. Participants were followed for side effects and adherence every 2 months either by a telephone call or a clinic visit. Blood was sampled for retinoid, carotenoid, and liver function analyses annually. beta-carotene and retinol were well tolerated during the follow-up period, which had a median of 1.5 years and a maximum of 3.3 years. Yellowing of the skin was seen in both beta-carotene arms. No differences were seen among arms or over time in incidence or severity of the other 15 monitored symptoms and signs or in serum liver function tests. Adherence was good: 83% of participants remained active on study at 1 year and 75% at 2 years. Serum beta-carotene increased from a prerandomization median concentration of 170 to 2100 ng/ml after 4 months of supplementation, and retinyl palmitate median levels more than tripled.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of the joint effects of alcohol and smoking on the risk of cancer across sites in the upper aerodigestive tract.

Abstract: A unified analysis of the combined effects of alcohol and smoking in cancers of the upper aerodigestive tract was conducted using polychotomous logistic regression to determine if, at the same level of exposure, risk varies significantly across pathological sites. Data from a case-control study in northern Italy include males with tumors of the oral cavity/pharynx, larynx, and esophagus and males admitted to the hospital for acute illnesses not related to alcohol and smoking. The combined alcohol and smoking risks for oral cavity/pharynx cancer in these data were significantly greater than those for either laryngeal or esophageal cancer, but esophageal cancer and laryngeal cancer could not be distinguished based on risk. The differences may lie in the presence of unspecified factors in the oral cavity and pharynx, but not in the other upper aerodigestive tract sites, which potentiate the effects of alcohol and smoking in the oral cavity/pharynx.

Ornithine decarboxylase and polyamines in colorectal neoplasia and mucosa.

Abstract: Ornithine decarboxylase (ODC) and polyamines are intimately involved in normal cellular proliferation and are likely to play a role in carcinogenesis. ODC activity and polyamine content were measured in tissue samples obtained during colonoscopy from 48 benign neoplastic polyps (20 tubular adenomas; 28 villous adenomas), 18 cancers (including 5 malignant polyps), and adjacent mucosa. ODC activity in polyp and cancer tissue specimens was higher than in adjacent mucosa in 75 and 83% of pairs, respectively. Similarly, putrescine, spermidine, and spermine contents were higher in the majority of polyps and cancers compared to adjacent mucosa. ODC activity and polyamine content in colonic mucosa from 10 patients without a history of colorectal neoplasia were not different from adjacent mucosal values in the patients with neoplasia. In conclusion, ODC and polyamines are elevated in the majority of colorectal neoplasms, but amounts in normal mucosa do not differentiate between patients with cancer, benign neoplastic polyps, and normal subjects.

ASPO Distinguished Achievement Award Lecture. Studies on the epidemiology and natural history of benign breast disease and breast cancer using nipple aspirate fluid.

Abstract: Nicholas L. Petrakis, M.D., was presented the American Society of Preventive Oncology's Distinguished Achievement Award at the Society's annual meeting on March 15, 1992, in Bethesda, Maryland. The basis for choosing Dr. Petrakis was his distinguished achievements for over 20 years in research and education concerning the etiology and prevention of cancer, with substantial emphasis on breast cancer. Dr. Petrakis obtained a Bachelor of Arts degree from Augustana College, Sioux Falls, South Dakota, and his Doctor of Medicine degree from Washington University, St. Louis, Missouri. He has held numerous principal positions at the University of California, beginning with a position with the U.S. Public Health Service, National Cancer Institute Laboratory of Experimental Oncology, and then the Cancer Research Institute, both at the University of California, San Francisco. Dr. Petrakis has held continuing appointments in the Department of Preventive Medicine and Department of Epidemiology and International Health, beginning as an Assistant Professor. He was subsequently promoted to Associate Professor and Professor of Preventive Medicine. During the years from 1978 to 1989, Dr. Petrakis was chair of the Department of Epidemiology and International Health. Since 1981 he has been Professor of Epidemiology, University of California, Berkeley, School of Public Health. In 1989 he became Professor Emeritus of Preventive Medicine and Epidemiology.(ABSTRACT TRUNCATED AT 250 WORDS)

A case-control study of element levels and cancer of the upper aerodigestive tract.

Abstract: A population-based case-control study was conducted in western Washington state to investigate possible dietary risk factors for laryngeal, esophageal, and oral cancers. Using results from a food frequency questionnaire, past dietary intakes of iron, zinc, and calcium were estimated for 661 cases and 466 controls. Clippings were also taken from the nails of both halluces to determine concentrations of iron, zinc, calcium, chromium, and cobalt in 507 of the cases and 434 of the controls. After adjustment for smoking, alcohol, and dietary beta-carotene and vitamin C intake, individuals who reported dietary intakes of iron and zinc in the upper quartile were less likely to develop cancers of the larynx and esophagus than were individuals with intakes in the lowest quartile [odds ratios (OR), 0.5 for iron and 0.1 for zinc]. However, there were no significant differences in zinc concentrations in nail tissue between subjects with these types of cancer and controls. Esophageal cancer cases had higher nail concentrations of iron and calcium than did controls (OR, 2.9 for high versus low quartiles of iron; OR, 2.6 for high versus low quartiles of calcium). Individuals who developed esophageal or oral cancer were more likely to have elevated cobalt concentrations in their nail tissue than were individuals without cancer (OR, 9.0 and 1.9 respectively, for high versus low quartiles). The results of this study suggest that there may be differences in mineral intake or metabolism between individuals who develop some carcinomas of the upper aerodigestive tract and those who do not.

A case control study of nutritional factors and cervical dysplasia.

Abstract: The association of nutritional factors with cervical dysplasia was examined through a case-control study. Analysis was conducted in 257 cases and 133 controls confirmed both by cytological examination and colposcopic findings. A 24-h dietary recall questionnaire was used to assess nutritional intake. Various risk factors (including age at first intercourse, number of sexual partners, parity, cigarette smoking, oral contraceptive use, human papillomavirus type 16 infection, and age and race) were adjusted for their potential confounding effects. While analyses were also performed to adjust for total calories, results were not changed significantly. Among the nutrients examined, vitamin A intake showed a significantly increased risk at the lowest quartile compared to the highest quartile, with an odds ratio of 2.2 (95% confidence interval, 1.2-4.2). A significant trend of increasing risk was also observed with lower intake of vitamin A (P = 0.05). Riboflavin showed increased risk at the two lower quartiles of intake with a trend test P value of 0.04. Increased risk was also found for lower intakes of vitamin C compared to the highest intake level. For folate, increased risk was found in the second highest quartile compared with the highest quartile with an odds ratio of 2.0 (95% confidence interval, 1.0-3.8). The calcium:phosphorus ratio showed an increased risk at the lowest level (odds ratio, 2.0; 95% confidence interval, 1.0-4.3). Insufficient intake of vitamin A, riboflavin, ascorbate, and folate is associated with an increased risk of cervical dysplasia.

Helicobacter pylori antibodies in areas of Italy at varying gastric cancer risk.

Abstract: In a survey of 930 adults aged 35-74 years randomly sampled from the general population of four areas of Italy, two at low and two at high risk for gastric cancer, plasma levels of Helicobacter pylori IgG antibodies were assayed in order to investigate associations with the geographical distribution of gastric cancer and other dietary and life-style factors, as assessed by personal interview. H. pylori positivity (antibody titer above or equal to 10 micrograms/ml), 45% overall, increased with age and was inversely associated with social class but showed little geographical variation or association with dietary variables and blood nutrients. H. pylori positivity was also associated with increased blood levels of pepsinogens, particularly pepsinogen II. The authors discuss these findings in relation to those from a previous case-control study of gastric cancer in the same areas.

Racial differences in restriction fragment length polymorphisms and messenger RNA inducibility of the human CYP1A1 gene.

Abstract: Recent studies have examined the relationship between genetic polymorphisms of the human cytochrome P-4501A1 (CYP1A1) gene and lung cancer susceptibility. We have quantified genotypic frequencies and measured gene expression in the CYP1A1 gene within racially diverse groups in order to determine the relationship between genotype and transcriptional regulation of the CYP1A1 gene. Lymphocytes were obtained from 68 individuals of European-American, African-American, and Asian descent, and CYP1A1 gene inducibility was measured in mitogen-stimulated cells. CYP1A1 gene inducibility was significantly lower in African-Americans than in European-Americans or Asians, while several other population parameters were found to have no effect on gene expression levels. Restriction fragment length polymorphism analysis of lymphocyte DNA following MspI restriction enzyme digestion revealed a significant difference in the frequencies of CYP1A1 genotypes between European-Americans and Asians. The only homozygous variants detected were of Asian descent. The frequencies of CYP1A1 genotypes in all races conformed to Hardy-Weinberg genotypic equilibrium. When CYP1A1 gene inducibility was compared to CYP1A1 genotype, no significant correlations were found. These studies, along with our previous survey of CYP1A1 gene expression in creosote-exposed workers, add further support to the use of CYP1A1 gene inducibility as a potential marker of polycyclic aromatic hydrocarbon exposure in human populations.