Paul T. Strickland

Association of nonmelanoma skin cancer and actinic keratosis with cumulative solar ultraviolet exposure in Maryland watermen

To establish the relationship between ultraviolet‐B radiation and squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and actinic keratosis (AK), a cross‐sectional prevalence survey was performed in a sample of 808 white, male watermen 30 years of age and older residing in the Eastern Shore of Maryland. A measure of personal cumulative ultraviolet‐B exposure was determined for each subject from data collected through interviews and field and laboratory measurements. A personal interview elicited skin type, medication history, and other factors. Clinical diagnoses and histologic confirmation were done for current and previously removed skin tumors. The ratio of subjects with SCC to subjects with BCC was approximately 1:1; however, the ratio of BCC to SCC was 1.25:1 because BCC cases were more prone to multiple lesions. Watermen with SCC or AK but not BCC had higher average annual ultraviolet‐B doses than age‐matched controls. This was particularly marked in watermen younger than 60 years of age. Logistic regression showed that an older age, childhood freckling, and blue eyes significantly increased the risk of the development of all three types of skin tumor. Ease of sunburning was associated with BCC and AK, but not with SCC. Watermen in the upper quartile of cumulative ultraviolet‐B exposure had a 2.5 times higher risk for the development of SCC when compared with the lower 3 quartiles. This suggests that high levels of ultraviolet‐B exposure are important in SCC occurrence. The risk of AK developing was 1.5 times higher for those whose cumulative ultraviolet‐B exposure exceeded the median. The relationship of BCC to cumulative ultraviolet‐B exposure was not clear and this suggests that different etiologic mechanisms operate for SCC and BCC.

Alcohol consumption, glutathione S-transferase M1 and T1 genetic polymorphisms and breast cancer risk

To evaluate the potential association between GSTM1 and GSTT1 genotypes and development of breast cancer, a hospital based case-control study was conducted in a South Korean study population consisting of 189 histologically confirmed incident breast cancer cases and their 189 age-matched control subjects with no present or previous history of cancer. A multiplex polymerase chain reaction method was used for the genotyping analyses and statistical evaluations were performed by unconditional logistic regression model. The GSTM1 null genotype was significantly associated with breast cancer risk in premenopausal women [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1-3.7], but not in the postmenopausal women (OR = 0.9, 95% CI = 0.5-1.9), nor in all women grouped together (OR = 1.3, 95% CI = 0.8-1.1). The GSTT1 null genotype posed a similar risk of breast cancer with an OR of 1.6 (95% CI = 1.0-2.5) for the total breast cancer group, OR of 1.7 (95% CI = 0.9-3.2) for pre-menopausal women, and OR of 1.3 (95% CI = 0.6-2.8) for post-menopausal women. The breast cancer risk associated with concurrent lack of both GSTM1 and GSTT1 genes was 2.2 (95% CI = 1.1-4.5), and the risk increased as the number of null genotype increased (P for trend = 0.03). When the data were stratified by the known risk factors of breast cancer, a significant interaction was observed between the GSTM1 genotypes and alcohol consumption (P for interaction = 0.03). An especially remarkable risk of breast cancer was observed for alcohol-consuming premenopausal women lacking both the GSTM1 and GSTT1 genes (OR = 5.3, 95% CI = 1.0-27.8) compared to those with both of the genes. Our findings thus suggest a novel gene-environment interaction which plays an important role in the individual susceptibility to breast cancer. p6

Urinary 1-hydroxypyrene and other PAH metabolites as biomarkers of exposure to environmental PAH in air particulate matter

Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) from occupational, environmental, medicinal and dietary sources. PAH metabolites in human urine can be used as biomarkers of internal dose to assess recent exposure to PAHs. The most widely used urinary PAH metabolites are 1-hydroxypyrene (1-OHP) or 1-hydroxypyrene-O-glucuronide (1-OHP-gluc), the major form of 1-OHP in human urine, because of their relatively high concentration and prevalence in urine and their relative ease of measurement. Elevated levels of 1-OHP or 1-OHP-gluc have been demonstrated in smokers, in patients receiving coal tar treatment (vs. pre-treatment), in postshift road pavers or coke oven workers, and in subjects ingesting charbroiled meat. This metabolite is found (at low levels) in most human urine samples, even in persons without apparent occupational or smoking exposure. Recent studies suggest that environmental exposure to PAHs (and air particles) is associated with increased excretion of 1-OHP-gluc or 1-OHP. These findings raise the possibility of using urinary concentration of 1-OHP-gluc, or another PAH metabolite, as a surrogate biomarker of exposure to airborne fine (sooty) particulate matter--the major source of PAHs in polluted air. Reported associations between ambient particulate matter concentrations and health effects among adults and children, including respiratory disease and mortality, indicate the need for biomarkers of fine particle exposure. If validated, such biomarkers would be useful in supplementing and refining exposure information obtained by ambient monitoring.

Dietary Benzo[a]Pyrene Intake and Risk of Colorectal Adenoma

We carried out a clinic-based case-control study specifically designed to address the hypothesis that dietary intake of polycyclic aromatic hydrocarbons (PAH) is associated with colorectal adenoma risk. We developed a food frequency questionnaire with detailed questions on meat-cooking methods and doneness levels and a benzo[a]pyrene (BaP) database (as a surrogate for total carcinogenic PAHs) based on the collection and analysis of a wide range of food samples. We estimated BaP intake derived from meat and from all foods to test its relationship with risk of colorectal adenomas. The median (10th and 90th percentiles) BaP intake in controls was 5 ng/d (0.2 and 66 ng/d) estimated from meat and 73 ng/d (35 and 140 ng/d) from all foods. In cases, median BaP intake was 17 ng/d (0.5 and 101 ng/d) from meat and 76 ng/d (44 and 163 ng/d) from all foods. Multivariate analysis was carried out on 146 cases and 228 controls. The odds ratios (95% confidence interval) for dietary BaP from meat with the first quintile as the reference group were 1.19 (0.51-2.80) for the second quintile, 1.71 (0.76-3.83) for the third quintile, 2.16 (0.96-4.86) for the fourth quintile, and 2.82 (1.24-6.43) for the fifth quintile (Ptrend = 0.01). Increased risk of colorectal adenomas was more strongly associated with BaP intake estimated from all foods: 2.61 (1.08-6.29) for the second quintile, 4.21 (1.79-9.91) for the third quintile, 2.45 (0.98-6.12) for the fourth quintile, and 5.60 (2.20-14.20) for the fifth quintile (Ptrend = 0.002). This study provides evidence that dietary BaP plays a role in colorectal adenoma etiology.

Nonmelanoma Skin Cancer and Risk for Subsequent Malignancy

BACKGROUND Individuals with a personal history of nonmelanoma skin cancer (NMSC) may have an increased risk of subsequent noncutaneous malignancies. To test this hypothesis, we carried out a community-based, prospective cohort study. METHODS In the CLUE (Give Us a Clue to Cancer and Heart Disease) II cohort, which was established in Washington County, MD, in 1989, the risk of new malignancies was compared among individuals with (n = 769) and without (n = 18,405) a personal history of NMSC (total n = 19,174) during a 16-year follow-up period. Pathologically confirmed NMSC (and other malignancies) were ascertained from the Washington County Cancer Registry. Cox regression analysis with time-dependent covariates was used to determine the hazard ratios (presented as multivariable-adjusted relative risks [RRs]) and 95% confidence intervals (CIs) of second primary malignancies associated with a previously confirmed NMSC diagnosis. All statistical tests were two-sided. RESULTS The crude incidence rate (per 10,000 person-years) of subsequent cancers other than NMSC among participants with a positive personal history of NMSC was 293.5 and with a negative history was 77.8. Compared with persons with no personal history of NMSC, those with such a history had a statistically significantly increased risk of being diagnosed with a subsequent cancer other than NMSC (RR = 1.99, 95% CI = 1.70 to 2.33) after adjusting for age, sex, body mass index, smoking status, and educational level. The association was observed for both basal cell carcinoma (multivariable-adjusted RR = 2.03, 95% CI = 1.70 to 2.42) and squamous cell carcinoma (multivariable-adjusted RR = 1.97, 95% CI = 1.50 to 2.59) of the skin. NMSC was a statistically significantly stronger cancer risk factor in younger age groups than in older age groups (P for interaction = .022). CONCLUSIONS This community-based, prospective cohort study provides evidence for an association between an NMSC diagnosis and an increased risk of subsequent cancer, even after adjusting for individual-level risk factors.

Ocular and Facial Skin Exposure to Ultraviolet Radiation in Sunlight: A Personal Exposure Model With Application to a Worker Population

A model of ocular and facial skin exposure to UVB is presented that combines interview histories of work activities, leisure activities, eyeglass wearing, and hat use with field and laboratory measurements of UV radiant exposure. Site-specific exposure is expressed as the product of personal ambient exposure, defined as the ambient exposure while an individual is exposed to sunlight, and factors that describe the ratio of site-specific to personal ambient exposure. Ocular exposure is further corrected by the UV attenuation of typical eyewear. The model was used to compute cumulative and yearly exposures in a population of 838 watermen who work on the Chesapeake Bay and are highly exposed to sunlight. The model was found to be predictive of conditions known to be caused by excessive sun exposure--skin elastosis, climatic droplet keratopathy, and squamous cell carcinoma--and has been useful in several epidemiological studies.

DNA adducts in urothelial cells: Relationship with biomarkers of exposure to arylamines and polycyclic aromatic hydrocarbons from tobacco smoke

Markers of exposure to polycyclic aromatic hydrocarbons (urinary 1‐hydroxypyrene‐glucuronide) and aromatic amines (4‐aminobiphenyl‐hemoglobin adducts), as well as urinary mutagenicity, were measured in 47 healthy smokers and 50 non‐smokers. DNA adducts were determined by P32‐postlabeling in the exfoliated bladder cells of 39 healthy subjects. Both 1‐hydroxypyrene‐glucuronide (1‐OHPG) and 4‐aminobiphenyl adducts (4‐ABP‐Hb) were associated with smoking habits, but only 4‐ABP‐Hb adducts were associated with consumption of black, air‐cured tobacco. The levels of 2 DNA adducts (numbers 2 and 4) in urothelial cells were clearly associated with 4‐ABP‐Hb adducts, in all subjects and in smokers. Levels of one of these DNA adducts (number 2) were also associated with 1‐hydroxypyrene‐glucuronide in urines, but in smokers the association was not statistically significant. Overall, these observations constitute further evidence of a role of arylamines in tobacco‐induced bladder cancer.

Exposure to traffic exhausts and oxidative DNA damage

Aims: To assess the relations between exposure to traffic exhausts and indicators of oxidative DNA damage among highway toll station workers. Methods: Cross-sectional study of 47 female highway toll station workers exposed to traffic exhausts and 27 female office workers as a reference group. Exposure assessment was based on average and cumulative traffic density and a biomarker of exposure, urinary 1-hydroxypyrene-glucuronide (1-OHPG). Urinary 8-hydroxydeoxyguanosine (8-OHdG) was used as a biomarker of oxidative DNA damage. Plasma nitric oxide (NO) was measured as an indicator of oxidative stress related to traffic exhaust exposure. Results: The mean concentration of urinary 8-OHdG was substantially higher among the exposed non-smokers (13.6 μg/g creatinine) compared with the reference non-smokers (7.3 μg/g creatinine; difference 6.3, 95% CI 3.0 to 9.6). The mean concentration of NO among the exposed (48.0 μmol/l) was also higher compared with the reference non-smokers (37.6 μmol/l; difference 10.4, 95% CI −0.4 to 21.2). In linear regression adjusting for confounding, a change in log(8-OHdG) was statistically significantly related to a unit change in log(1-OHPG) (β = 0.372, 95% CI 0.081 to 0.663). Conclusions: Results indicate that exposure to traffic exhausts increases oxidative DNA damage. Urinary 8-OHdG is a promising biomarker of traffic exhaust induced oxidative stress.

An automated, handheld biosensor for aflatoxin

A new immunoaffinity fluorometric biosensor has been developed for detecting and quantifying aflatoxins, a family of potent fungi-produced carcinogens that are commonly found in a variety of agriculture products. They have also been cited as a biological agent under weapons development. The handheld, self-contained biosensor is fully automatic, highly sensitive, quick, quantitative, and requires no special storage. Approximately 100 measurements can be made before refurbishment is required, and concentrations from 0.1 parts per billion (ppb) to 50 ppb can be determined in <2 min with a 1 ml sample volume. The device operates on the principles of immunoaffinity for specificity and fluorescence for a quantitative assay. The analytic procedure is flexible so that other chemical and biological analytes could be detected with minor modifications to the current device. Advances in electro-optical components, electronics, and miniaturized fluidics were combined to produce this reliable, small, and versatile instrument.

Higher urine 1-hydroxy pyrene glucuronide (1-OHPG) is associated with tobacco smoke exposure and drinking maté in healthy subjects from Rio Grande do Sul, Brazil

BackgroundThe highest rates of esophageal squamous cell carcinoma (ESCC) in Brazil occur in Rio Grande do Sul, the most southern state, which has incidence rates of 20.4/100,000/year for men and 6.5/100,000/year for women. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) through tobacco smoke and other sources may increase the risk of ESCC. The aims of the current study were to investigate the degree and sources of PAH exposure of the inhabitants of this region of southern Brazil.MethodsTwo hundred healthy adults (half smokers, half non smokers, half male and half female) were recruited, given a standardized questionnaire, and asked to provide a urine sample for measurement of 1-hydroxypyrene glucuronide (1-OHPG), a PAH metabolite). Urine 1-OHPG concentrations were measured using immunoaffinity chromatography and synchronous fluorescence spectroscopy and urine cotinine was measured using a dipstick test. We examined factors associated with 1-OHPG concentration using Wilcoxon tests and multiple linear regression.ResultsUrine 1-hydroxypyrene glucuronide (1-OHPG) was successfully measured on 199 subjects. The median (interquartile range) of urine 1-OHPG in the 199 participants was 2.09 pmol/mL (0.51, 5.84). Tobacco smoke exposure and maté drinking were statistically significantly associated with higher urine 1-OHPG concentrations in the multivariate linear regression model.ConclusionTobacco smoke and maté both contribute to high levels of benzo[a]pyrene exposure in the people of southern Brazil. This high PAH exposure may contribute to the high rates of ESCC observed in this population. The increased urine 1-OHPG concentrations associated with maté suggest that contaminants, not just thermal injury, may help explain the increased risk of ESCC previously reported for maté consumption.