Faculty Bibliography

1,3-Butadiene (BD) is an important industrial chemical and pollutant. Its ability to induce genetic damage and cause hematological malignancies in humans is controversial. We have examined chromosome damage by fluorescence in situ hybridization (FISH) and mutations in the HPRT gene in the blood of Chinese workers exposed to BD. Peripheral blood samples were collected and cultured from 39 workers exposed to BD (median level 2 ppm, 6 h time-weighted average) and 38 matched controls in Yanshan, China. No difference in the level of aneuploidy or structural changes in chromosomes 1, 7, 8, and 12 was detected in metaphase cells from exposed subjects in comparison with matched controls, nor was there an increase in the frequency of HPRT mutations in the BD-exposed workers. Because genetic polymorphisms in glutathione S-transferase (GST) enzymes and microsomal epoxide hydrolase (EPHX1) may affect the genotoxic effects of BD and its metabolites, we also related chromosome alterations and gene mutations to GSTT1, GSTM1 and EPHX1 genotypes. Overall, there was no effect of variants in these genotypes on numerical or structural changes in chromosomes 1, 7, 8 and 12 or on HPRT mutant frequency in relation to BD exposure, but the GST genotypes did influence background levels of both hyperdiploidy and HPRT mutant frequency. In conclusion, our data show no increase in chromosomal aberrations or HPRT mutations among workers exposed to BD, even in potentially susceptible genetic subgroups. The study is, however, quite small and the levels of BD exposure are not extremely high, but our findings in China do support those from a similar study conducted in the Czech Republic. Together, these studies suggest that low levels of occupational BD exposure do not pose a significant risk of genetic damage

OBJECTIVES: We carried out a detailed exposure assessment of benzene and toluene in two shoe factories in Tianjin, China. Our goal was to identify workers with a broad range of benzene exposures, for an epidemiologic study relating exposure to early biologic effects. METHODS: A comprehensive exposure survey program was initiated. Over a period of 16 months, 2783 personal solvent exposure samples were collected in two workplaces from 250 workers. Mixed-effects models were used to identify factors affecting exposure. Principal component analyses (PCA) and subsequent regression analyses on the scores of the identified principal components were used to relate potential co-exposures to various exposure sources present in the workplace. RESULTS: The mean benzene exposure level was 21.86 p.p.m. (10th-90th percentiles 5.23-50.63 p.p.m.) in the smaller shoe factory (factory A) and 3.46 p.p.m. (10th-90th percentiles 0.20-7.00 p.p.m.) in the larger shoe factory (factory B). Within-factory exposure levels differed among job titles and were higher for subjects directly involved in handling glues. In contrast, mean toluene levels were relatively similar in the two factories (factory A, 9.52 p.p.m.; factory B, 15.88 p.p.m.). A seasonal trend was identified for both benzene and toluene in factory B. This could be explained in part by changes in air movement and ventilation patterns occurring during the year. A seasonal trend was not present in the smaller shoe factory, where general ventilation was absent. Supplemental analysis showed that exposure levels to other hydrocarbons were low (< or =5 p.p.m.), less than 5% of their respective ACGIH threshold limit values, and generally comparable in the two factories. PCA showed that co-exposures in factory B could largely be explained by glue sources that were used in distinct areas in the workplace. CONCLUSIONS: We demonstrated the occurrence of a broad range of benzene exposure levels in two shoe manufacturing factories in Tianjin, China. Benzene and toluene exposures were determined in part by the degree of contact with glues, the benzene and toluene content of each glue, air movement and ventilation patterns. The availability of long-term monthly personal monitoring data provides an excellent opportunity to estimate individual exposures at different times during the 1 yr period of observation

Possession of the fast metabolizing alleles for alcohol dehydrogenase (ADH), ADH1B*2 and ADH1C*1, and the null allele for aldehyde dehydrogenase (ALDH), ALDH2*2, results in increased acetylaldehyde levels and is hypothesized to increase the risk of head and neck cancer. To examine this association, the authors undertook a Human Genome Epidemiology review on these three genes and a pooled analysis of published studies on ADH1C. The majority of Asians had the fast ADH1B*2 and ADH1C*1 alleles, while the majority of Caucasians had the slow ADH1B*1/1 and ADH1C*1/2 genotypes. The ALDH2*2 null allele was frequently observed among Asians, though it was rarely observed in other populations. In a pooled analysis of data from seven case-control studies with a total of 1,325 cases and 1,760 controls, an increased risk of head and neck cancer was not observed for the ADH1C*1/2 genotype (odds ratio = 1.00, 95% confidence interval: 0.81, 1.23) or the ADH1C*1/1 genotype (odds ratio = 1.14, 95% confidence interval: 0.92, 1.41). Increased relative risks of head and neck cancer were reported for the ADH1B*1/1 and ALDH2*1/2 genotypes in several studies. Recommendations for future studies include larger sample sizes and incorporation of relevant ADH and ALDH genes simultaneously, as well as other genes. These considerations suggest the potential for the organization of a consortium of investigators conducting studies in this field

BACKGROUND & AIMS: The relationship between distal and proximal colonic findings is uncertain. Thus, there is no consensus on which findings on screening flexible sigmoidoscopy should trigger colonoscopy. METHODS: We analyzed data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to assess the relationship between distal and proximal colonic findings. RESULTS: A total of 8802 subjects had an abnormal baseline sigmoidoscopy and colonoscopy follow-up. Subjects with <10-mm single or multiple tubular adenomas had similar risks for advanced proximal neoplasia as subjects with hyperplastic polyps or other benign lesions (3%-5%). Subjects with large (>or=10 mm), villous, or severely dysplastic distal adenomas had similarly elevated risks for advanced proximal neoplasia (11%-12%). Multivariate logistic modeling showed a significantly increased risk for advanced proximal neoplasia associated with the presence of a large tubular (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.0-3.4) or villous distal adenoma (OR, 2.7; 95% CI, 2.1-3.5) but not with the presence of one (OR, 1.05; 95% CI, 0.8-1.3) or multiple (OR, 0.8; 95% CI, 0.5-1.2) <10-mm tubular distal adenomas. CONCLUSIONS: Among subjects with a polypoid lesion on screening flexible sigmoidoscopy, those with small tubular distal adenomas are at similar risk for advanced proximal neoplasia as those without distal adenomas. Subjects with a large, villous, or dysplastic distal adenoma are at increased risk. A strategy that encourages individuals with small tubular adenomas on sigmoidoscopy to undergo follow-up colonoscopy and excludes those with nonadenomatous lesions is of questionable validity, because both groups are at similar risk for advanced proximal neoplasia

BACKGROUND: Many U.S. factory workers are exposed to formaldehyde. Although increased risks for leukemia have been found in medical workers and other professionals exposed to formaldehyde, studies in industrial workers, who are thought to have higher exposures, have shown inconsistent associations. We extended follow-up of a cohort of industrial workers to evaluate the association between formaldehyde exposure and lymphohematopoietic cancers. METHODS: The cohort consisted of 25 619 workers (865 708 person-years) employed before January 1, 1966, at one of 10 U.S. industrial plants and followed through December 31, 1994. We analyzed formaldehyde exposure (peak exposure, average exposure intensity, cumulative exposure, and duration of exposure) and mortality from lymphohematopoietic malignancies using standardized mortality ratios and relative risks and 95% confidence intervals (CIs) based on Poisson regression. Statistical tests were two-sided. RESULTS: Among the cohort, there were 178 deaths from lymphohematopoietic malignancies. Relative risks for leukemia (69 deaths), particularly for myeloid leukemia (30 deaths), increased with formaldehyde exposure. Compared with workers exposed to low peak levels of formaldehyde (0.1-1.9 ppm), relative risks for myeloid leukemia were 2.43 (95% CI = 0.81 to 7.25) and 3.46 (95% CI = 1.27 to 9.43) for workers exposed to peak levels of 2.0-3.9 ppm and > or = 4.0 ppm, respectively (P(trend) =.009). Compared with workers exposed to low levels of average exposure intensity of formaldehyde (0.1-0.4 ppm), workers exposed to 0.5-0.9 ppm and > or = 1.0 ppm average intensity had relative risks of 1.15 (95% CI = 0.41 to 3.23) and 2.49 (95% CI = 1.03 to 6.03), respectively (P(trend) =.088). The relative risk for leukemia was not associated with cumulative exposure but was weakly associated with duration of exposure. Relative risks for Hodgkin's disease also increased with formaldehyde exposure. CONCLUSIONS: Exposure to formaldehyde may cause leukemia, particularly myeloid leukemia, in humans. However, results from other investigations are mixed, suggesting caution in drawing definitive conclusions

Shipbuilding workers are exposed to a variety of genotoxic compounds including polycyclic aromatic hydrocarbons (PAHs). A limited number of studies have been conducted to evaluate biomarkers related to PAH exposure in painters in the shipyard industry. We examined this in 208 workers recruited from a shipyard located in South Korea. Employees were grouped into three exposure groups: (1) 111 painters using coal tar paints, (2) 70 painters using general paints, and (3) 27 on-site controls using no paints. Levels of urinary 1-hydroxypyrene glucuronide (1-OHPG), as internal dose of PAH exposure, were measured by synchronous fluorescence spectroscopy. Glutathione S-transferase (GST) M1 and T1 genotypes were assessed by a multiplex polymerase chain reaction (PCR)-based method, aromatic-DNA adducts in peripheral white blood cells were measured by 32P-postlabeling, and glycophorin A (GPA) variant frequencies in red blood cells were assessed by flow cytometry. Information on demographic characteristics, smoking habits, diet, job title and use of personal protective equipment (e.g. respiratory and dermal) were collected by self-administered questionnaire. Average urinary 1-OHPG levels in coal tar paint (2.24 micromol/mol creatinine) and general paint (1.38 micromol/mol creatinine) users were significantly higher than in on-site controls (0.62 micromol/mol creatinine) (P<0.001). Paint use, irrespective of the type of paints, and smoking (yes/no) were positively associated with urinary 1-OHPG levels, whereas green tea consumption (yes/no) was negatively associated with the 1-OHPG levels. No significant effect in the 1-OHPG levels were observed for the GSTM1 and GSTT1 genotypes. Aromatic-DNA adduct levels tended to be higher in coal tar paint users (P = 0.06) and painters (P = 0.07) compared to on-site controls. No differences in adduct levels were observed, between the two groups of painters, and the combined group showed greater adduct levels than on-site controls (P = 0.05). GPA mutation frequencies measured in 55 individuals with MN heterozygote genotypes were not significantly different among the three exposure groups, and no correlation was observed between urinary 1-OHPG levels and aromatic-DNA adducts or GPA mutation frequency. These results suggest that painters in the shipyard were exposed to significant amounts of PAHs and possibly to other genotoxic aromatic compounds, and that urinary 1-OHPG may be a potential biomarker of PAH exposure in this population

The work history information from a population-based case-control study conducted in Puerto Rico was analyzed using a job exposure matrix to investigate the relationship between occupational exposures and cancers of the oral cavity or pharynx. After adjustment for age, alcohol, smoking, and residence in a logistic model, the risk for cancer of the oral cavity, but not the pharynx, was significantly elevated among farm workers in the sugarcane industry (OR = 4.4, 95% CI = 1.4-13.6). An exposure-response trend was seen for cumulative exposure to solvents, with an OR = 3.2 (95% CI = 0.8-12.6) in the highest exposure category. The overall contribution to the risk of cancer of the oral cavity or pharynx associated with occupational exposures in Puerto Rico appears to be small, however, the elevated risks were seen among sugarcane farmers and subjects with high cumulative exposure to solvents

BACKGROUND: Cytochrome P450 2E1 (CYP2E1) and NAD(P)H:quinone oxidoreductase (NQO1) catalyze the activation of some environmental procarcinogens present in tobacco smoke (i.e. nitrosoamines and heterocyclic amines). We conducted a hospital based case-control study to evaluate the potential association between genetic polymorphisms of CYP2E1 (C1019T in the 5' flanking region) and NQO1 (C609T in exon 6) and bladder cancer risk in Asian population. METHODS: The study population was comprised of 218 histologically confirmed prevalent bladder cancer cases and 199 controls without cancer or systemic illness. PCR-restriction fragment length polymorphism based methods were used for the genotyping analyses and unconditional logistic regression model for the statistical evaluations. RESULTS: The risk of bladder cancer increased with the amount of smoking (P for trend < 0.01). The frequency of CYP2E1 c1/c1 genotype was significantly higher in bladder cancer patients (57.9%) than in the controls (47.9%) (OR = 1.8, 95% CI = 1.1-2.9). Similarly, the NQO1 C/C genotypes were significantly more prevalent in the patients (45.8%) than in the controls (37.6%) (OR = 1.6, 95% CI = 1.0-2.7). The risk for bladder cancer increased with the number of the putative risk genotypes (P for trend = 0.03); the most remarkable risk was observed for heavy smokers with both CYP2E1 c1/c1 and NQO1 C/C genotypes (OR = 13.8, 95% CI = 3.9-48.6) when compared to non/light smokers with other genotypes. CONCLUSION: Our findings suggest that CYP2E1 and NQO1 genotypes may play an important role in development of smoking related bladder cancer among Korean men

Alcohol consumption is a major risk factor for cancers of the mouth and pharynx (oral cancer), but the differential risks by beverage type are unclear. In this 1992-1995 study, the authors examined oral cancer risk in Puerto Rico, comparing alcohol intake among 286 male cases aged 21-79 years and 417 population-based male controls, frequency matched by age. Heavy consumers of liquor (>/=43 drinks per week) had strongly increased risks of oral cancer (odds ratio = 6.4, 95% confidence interval: 2.4, 16.8); beer/wine showed only modest effects. Among liquor drinkers, risks were consistently greater for those who drank straight (undiluted) liquor than for those who usually drank mixed (diluted) liquor (odds ratio = 4.0, 95% confidence interval: 2.4, 6.7). Risks associated with combined exposure to tobacco were also more pronounced when subjects drank liquor straight. The elevated risks associated with drinking homemade rum were similar to those for other types of liquor. These results suggest that alcohol concentration is a risk factor for oral cancer independent of the total quantity of alcohol consumed

BACKGROUND: Although dietary fibre has been reported to have no association with colorectal adenoma and cancer, in some studies this topic remains controversial. METHODS: We used a 137-item food frequency questionnaire to assess the relation of fibre intake and frequency of colorectal adenoma. The study was done within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomised controlled trial designed to investigate methods for early detection of cancer. In our analysis, we compared fibre intake of 33971 participants who were sigmoidoscopy-negative for polyps, with 3591 cases with at least one histologically verified adenoma in the distal large bowel (ie, descending colon, sigmoid colon, or rectum). Odds ratios were estimated by logistic regression analysis. FINDINGS: High intakes of dietary fibre were associated with a lower risk of colorectal adenoma, after adjustment for potential dietary and non-dietary risk factors. Participants in the highest quintile of dietary fibre intake had a 27% (95% CI 14-38, p(trend)=0.002) lower risk of adenoma than those in the lowest quintile. The inverse association was strongest for fibre from grains and cereals and from fruits. Risks were similar for advanced and non-advanced adenoma. Risk of rectal adenoma was not significantly associated with fibre intake. INTERPRETATION: Dietary fibre, particularly from grains, cereals, and fruits, was associated with decreased risk of distal colon adenoma