The effects of exposure to solar radiation on human health.

This assessment by the Environmental Effects Assessment Panel (EEAP) of the Montreal Protocol under the United Nations Environment Programme (UNEP) evaluates the effects of ultraviolet (UV) radiation on human health within the context of the Montreal Protocol and its Amendments. We assess work published since our last comprehensive assessment in 2018. Over the last four years gains have been made in knowledge of the links between sun exposure and health outcomes, mechanisms, and estimates of disease burden, including economic impacts. Of particular note, there is new information about the way in which exposure to UV radiation modulates the immune system, causing both harms and benefits for health. The burden of skin cancer remains high, with many lives lost to melanoma and many more people treated for keratinocyte cancer, but it has been estimated that the Montreal Protocol will prevent 11 million cases of melanoma and 432 million cases of keratinocyte cancer that would otherwise have occurred in the United States in people born between 1890 and 2100. While the incidence of skin cancer continues to rise, rates have stabilised in younger populations in some countries. Mortality has also plateaued, partly due to the use of systemic therapies for advanced disease. However, these therapies are very expensive, contributing to the extremely high economic burden of skin cancer, and emphasising the importance and comparative cost-effectiveness of prevention. Photodermatoses, inflammatory skin conditions induced by exposure to UV radiation, can have a marked detrimental impact on the quality of life of sufferers. More information is emerging about their potential link with commonly used drugs, particularly anti-hypertensives. The eyes are also harmed by over-exposure to UV radiation. The incidence of cataract and pterygium is continuing to rise, and there is now evidence of a link between intraocular melanoma and sun exposure. It has been estimated that the Montreal Protocol will prevent 63 million cases of cataract that would otherwise have occurred in the United States in people born between 1890 and 2100. Despite the clearly established harms, exposure to UV radiation also has benefits for human health. While the best recognised benefit is production of vitamin D, beneficial effects mediated by factors other than vitamin D are emerging. For both sun exposure and vitamin D, there is increasingly convincing evidence of a positive role in diseases related to immune function, including both autoimmune diseases and infection. With its influence on the intensity of UV radiation and global warming, the Montreal Protocol has, and will have, both direct and indirect effects on human health, potentially changing the balance of the risks and benefits of spending time outdoors.

Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2021.

The Environmental Effects Assessment Panel of the Montreal Protocol under the United Nations Environment Programme evaluates effects on the environment and human health that arise from changes in the stratospheric ozone layer and concomitant variations in ultraviolet (UV) radiation at the Earth's surface. The current update is based on scientific advances that have accumulated since our last assessment (Photochem and Photobiol Sci 20(1):1-67, 2021). We also discuss how climate change affects stratospheric ozone depletion and ultraviolet radiation, and how stratospheric ozone depletion affects climate change. The resulting interlinking effects of stratospheric ozone depletion, UV radiation, and climate change are assessed in terms of air quality, carbon sinks, ecosystems, human health, and natural and synthetic materials. We further highlight potential impacts on the biosphere from extreme climate events that are occurring with increasing frequency as a consequence of climate change. These and other interactive effects are examined with respect to the benefits that the Montreal Protocol and its Amendments are providing to life on Earth by controlling the production of various substances that contribute to both stratospheric ozone depletion and climate change.

A risk prediction model for the development of subsequent primary melanoma in a population-based cohort.

BACKGROUND: Guidelines for follow-up of patients with melanoma are based on limited evidence. OBJECTIVES: To guide skin surveillance, we developed a risk prediction model for subsequent primary melanomas, using demographic, phenotypical, histopathological, sun exposure and genomic risk factors. METHODS: Using Cox regression frailty models, we analysed data for 2613 primary melanomas from 1266 patients recruited to the population-based Genes, Environment and Melanoma study in New South Wales, Australia, with a median of 14 years' follow-up via the cancer registry. Discrimination and calibration were assessed. RESULTS: The median time to diagnosis of a subsequent primary melanoma decreased with each new primary melanoma. The final model included 12 risk factors. Harrell's C-statistic was 0·73 [95% confidence interval (CI) 0·68-0·77], 0·65 (95% CI 0·62-0·68) and 0·65 (95% CI 0·61-0·69) for predicting second, third and fourth primary melanomas, respectively. The risk of a subsequent primary melanoma was 4·75 times higher (95% CI 3·87-5·82) for the highest vs. the lowest quintile of the risk score. The mean absolute risk of a subsequent primary melanoma within 5 years was 8·0 ± SD 4.1% after the first primary melanoma, and 46·8 ± 15·0% after the second, but varied substantially by risk score. CONCLUSIONS: The risk of developing a subsequent primary melanoma varies considerably between individuals and is particularly high for those with two or more primary melanomas. The risk prediction model and its associated nomograms enable estimation of the absolute risk of subsequent primary melanoma, on the basis of on an individual's risk factors, and can be used to tailor surveillance intensity, communicate risk and provide patient education. What's already known about this topic? Current guidelines for the frequency and length of follow-up to detect new primary melanomas in patients with one or more previous primary melanomas are based on limited evidence. People with one or more primary melanomas have, on average, a higher risk of developing another primary invasive melanoma, compared with the general population, but an accurate way of estimating individual risk is needed. What does this study add? We provide a comprehensive risk prediction model for subsequent primary melanomas, using data from 1266 participants with melanoma (2613 primary melanomas), over a median 14 years' follow-up. The model includes 12 risk factors comprising demographic, phenotypical, histopathological and genomic factors, and sun exposure. It enables estimation of the absolute risk of subsequent primary melanomas, and can be used to tailor surveillance intensity, communicate individual risk and provide patient education.

Skin Cancer Epidemiology and Sun Protection Behaviors Among Native Americans.

We read, with interest, Maarouf et al's study, Skin cancer epidemiology and sun protection behaviors among Native Americans (J Drugs Dermatol. 2019; 18(5):420- 423), which provided insight regarding sun protective behaviors among American Indians (AIs).1 At the University of New Mexico (UNM) School of Medicine Department of Dermatology we are particularly invested in using such data to address the healthcare disparities we observe regarding New Mexican AI access to care.

Genetic factors associated with naevus count and dermoscopic patterns: preliminary results from the Study of Nevi in Children (SONIC).

BACKGROUND: Melanocytic naevi are an important risk factor for melanoma. Naevi with distinct dermoscopic patterns can differ in size, distribution and host pigmentation characteristics. OBJECTIVES: We examined MC1R and 85 other candidate loci in a cohort of children to test the hypothesis that the development and dermoscopic type of naevi are modulated by genetic variants. METHODS: Buccal DNAs were obtained from a cohort of 353 fifth graders (mean age 10·4 years). Polymorphisms were chosen based on a known or anticipated role in naevi and melanoma. Associations between single-nucleotide polymorphisms (SNPs) and baseline naevus count were determined by multivariate regression adjusting for sex, race/ethnicity and sun sensitivity. Dermoscopic images were available for 853 naevi from 290 children. Associations between SNPs and dermoscopic patterns were determined by polytomous regression. RESULTS: Four SNPs were significantly associated with increasing (IRF4) or decreasing (PARP1, CDK6 and PLA2G6) naevus count in multivariate shrinkage analyses with all SNPs included in the model; IRF4 rs12203952 showed the strongest association with log naevus count (relative risk 1·56, P < 0·001). Using homogeneous naevi as the reference, IRF4 rs12203952 and four other SNPs in TERT, CDKN1B, MTAP and PARP1 were associated with either globular or reticular dermoscopic patterns (P < 0·05). CONCLUSIONS: Our results provide evidence that subsets of naevi defined by dermoscopic patterns differ in their associations with germline genotypes and support the hypothesis that dermoscopically defined subsets of naevi are biologically distinct. These results require confirmation in larger cohorts. If confirmed, these findings will improve the current knowledge of naevogenesis and assist in the identification of individuals with high-risk phenotypes.

Double-strand breaks and tumorigenesis.

The establishment of connections between biochemical defects and clinical disease is a major goal of modern molecular genetics. In this review, we examine the current literature that relates defects in the two major DNA double-strand-break repair pathways--homologous recombination and nonhomologous end-joining--with the development of human tumors. Although definitive proof has yet to be obtained, the current literature is highly suggestive of such a link.

Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review.

DNA repair is a system of defenses designed to protect the integrity of the genome. Deficiencies in this system likely lead to the development of cancer. The epidemiology of DNA repair capacity and of its effect on cancer susceptibility in humans is, therefore, an important area of investigation. We have summarized all of the published epidemiologic studies on DNA repair in human cancer through 1998 (n = 64) that addressed the association of cancer susceptibility with a putative defect in DNA repair capacity. We have considered study design, subject characteristics, potential biases, confounding variables, and sources of technical variability. Assays of DNA repair capacity used, to date, can be broadly grouped into five categories: 1) tests based on DNA damage induced with chemicals or physical agents, such as the mutagen sensitivity assay, the G(2)-radiation assay, induced micronuclei, and the Comet assay; 2) indirect tests of DNA repair, such as unscheduled DNA synthesis; 3) tests based on more direct measures of repair kinetics, such as the host cell reactivation assay; 4) measures of genetic variation associated with DNA repair; and 5) combinations of more than one category of assay. The use of such tests in human populations yielded positive and consistent associations between DNA repair capacity and cancer occurrence (with odds ratios in the range of 1. 4-75.3, with the majority of values between 2 and 10). However, the studies that we have reviewed have limitations, including small sample size, "convenience" controls, the use of cells different from the target organ, and the use of mutagens that do not occur in the natural environment. The evolving ability to study polymorphisms in DNA repair genes may contribute to new understandings about the mechanisms of DNA repair and the way in which DNA repair capacity affects the development of cancer.

Screening for cutaneous melanoma by skin self-examination.

BACKGROUND: Although some evidence indicates that early detection protects against the development of lethal melanoma, no randomized clinical trials have been conducted to measure the efficacy of early detection (or screening) in preventing death from this disease. Since melanoma incidence in the United States is relatively rare, a randomized clinical trial to test the efficacy of screening would be extremely expensive. PURPOSE: As an alternative to a randomized clinical trial, we conducted a population-based, case-control study to investigate whether early detection through skin self-examination (SSE) is associated with a decreased risk of lethal melanoma (includes the presence of advanced disease with distant metastases in addition to death from melanoma). METHODS: SSE (conducting a careful, deliberate, and purposeful examination of the skin) was assessed in all subjects by use of a structured questionnaire and personal interviews. The major exposure variable, SSE, was defined following focus-group interviews with melanoma patients and healthy control subjects. The final study population consisted of 1199 Caucasian residents of the state of Connecticut enrolled from January 15, 1987, through May 15, 1989; 650 individuals were newly diagnosed with cutaneous melanoma, and the remaining 549 individuals were age- and sex-frequency matched control subjects from the general population. During the study interviews, nevi on the arms and backs of subjects were counted. In 5 years of follow-up (through March 1994), 110 lethal cases of melanoma were identified. The study design allowed separate estimation of the impact of SSE on reduced melanoma incidence (primary prevention) and survival among incident cases (secondary prevention). Odds ratios (ORs) were used to measure the associations between SSE and melanoma and between SSE and lethal melanoma. RESULTS: SSE, practiced by only 15% of all subjects, was associated with a reduced risk of melanoma incidence (adjusted OR = 0.66; 95% confidence interval [CI] = 0.44-0.99; comparing case patients with control subjects). The data indicated further that SSE may reduce the risk of advanced disease among melanoma patients (unadjusted risk ratio = 0.58; 95% CI = 0.31-1.11); however, longer follow-up is required to confirm this latter estimate. If both estimates are correct, they suggest, in combination, that SSE may reduce mortality from melanoma by 63% (adjusted OR = 0.37; 95% CI = 0.16-0.84; comparing lethal cases with general population controls). CONCLUSIONS AND IMPLICATIONS: SSE may provide a useful and inexpensive screening method to reduce the incidence of melanoma. SSE may also reduce the development of advanced disease. The results of this study need to be replicated before strategies to increase the practice of SSE are further developed and promoted.

Prediabetes: The Variation between HbA1c and Fasting Plasma Glucose.

PURPOSE: The prevalence of Diabetes Type 2 is on the rise internationally. Currently, Fasting Plasma Glucose (FPG) and HbA1c are both used to determine if an individual is diabetic or prediabetic. We aimed to describe the prevalence of diabetes, prediabetes, and glycemic control in a population-based sample of elderly Hispanic and non-Hispanic White participants in New Mexico. METHODS: To do this, we compared HbA1c with FPG using Chi-Square analysis across gender and ethnicity to provide information for future health care policy. We also performed non-parametric regression using a locally weighted smoothing technique to investigate the relationship between FPG and HbA1c levels. RESULTS: Our analysis identifies a large variation between the sensitivity of HbA1c and FPG in the identification of both prediabetes and diabetes. Interestingly, 95% of diabetics defined by FPG are also defined by HbA1c, representing overlap between the two measures. When comparing the prevalence of prediabetes between the two measures, the overlap of FPG with HbA1c was only 30% and HbA1c identifies more individuals as prediabetic than FPG. Prevalence of diabetes was also higher when defined by HbA1c compared to FPG and the overall agreement between HbA1c and FPG appears to be poor particularly by sex and ethnicity (K=0.22-0.34). Glycemic control was poor overall with Hispanics displaying a larger amount of uncontrolled diabetes. CONCLUSION: We compared HbA1c and FPG by gender and ethnicity and showed both measures of diabetes differ in their sensitivity across ethnic groups. Our results suggest that using HbA1c, rather than FPG, results in higher rates of prediabetes and diabetes, a finding with numerous implications for health care practice.

Histopathologic recognition and grading of dysplastic melanocytic nevi: an interobserver agreement study.

Before the controversies surrounding dysplastic melanocytic nevi are resolved, dermatopathologists must be able to reliably distinguish dysplastic nevi from common acquired nevi and malignant melanoma. To establish whether grading of melanocytic dysplasia has any biologic relevance, dermatopathologists must be able to consistently recognize two or more grades of atypia. We studied the concordance among five dermatopathologists for recognition and grading of 60 nevomelanocytic lesions. Ten cases from each of the following categories of melanocytic proliferation were retrieved from the Massachusetts General Hospital files: 1) common melanocytic nevi, 2) melanocytic nevi with features of dysplastic nevi, 3) dysplastic nevi with slight cytologic atypia, 4) dysplastic nevi with moderate cytologic atypia, 5) dysplastic nevi with severe cytologic atypia, and 6) primary malignant melanoma. The slides were reviewed independently; no discussion of diagnostic criteria preceded the review. Overall concordance for diagnosing dysplastic nevi was 77%, with a kappa statistic of 0.55-0.84. Furthermore, in grading dysplastic nevi, experienced dermatopathologists had a concordance ranging from 35% to 58% (kappa value 0.38-0.47). Those with less experience in grading dysplastic nevi had a concordance of 16-65% (kappa value 0.05-0.24). The five observers in this study reliably distinguished dysplastic nevi from common acquired nevi and malignant melanoma. Further refinement of the criteria for grading of nevo-melanocytic dysplasia and experience in grading are critical for accuracy in subcategorization of dysplastic nevi. Consistent, reproducible subcategorization of dysplastic nevi is a requisite before the issue of biologic or prognostic relevance of grading (dysplastic nevi) can be addressed. This study supports the validity of existing criteria for the diagnosis of dysplastic nevi because the problems in diagnosis were at the limits of the spectrum, namely, discrimination of slightly atypical dysplastic nevi from common nevi and severely atypical dysplastic nevi from radial growth phase melanoma.

Poly(ADP-ribose) polymerase in human breast cancer: a case-control analysis.

The importance of a genetic polymorphism (A/B allele) of poly(ADP-ribose) polymerase (PARP) pseudogene on chromosome 13q34-qter, and PARP enzyme activities in the development of human breast cancer were evaluated in a cancer case-control study. A total of 309 Caucasian women (> or = 50 years old) were evaluated for the PARP genotype, 70 of whom had histologically confirmed breast cancer, 128 women with benign breast diseases as study controls, and 111 reference controls. Age was significantly associated with case-control status (p < 0.0001), but family history of breast cancer, age at menarche, age at first live birth and parity were not. The frequency of the PARP B allele was similar in breast cancer cases (0.14), study controls (0.13), and reference controls (0.15). In a subset of 14 breast cancer cases and 32 study controls, the mean PARP enzyme activities (induced by H2O2 or oligonucleotide) were observed to be lower in cancer cases; an age-adjusted odds ratio of 3.40 (95% confidence interval = 0.70-19.54) for the below-median oligonucleotide-induced PARP was suggestive of an association. In subjects with the AB or BB genotype, the mean H2O2-induced PARP enzyme activity was significantly higher (p = 0.02, adjusted for case-control status and age) compared with that in subjects with the AA genotype. These findings indicate that: (a) the genetic polymorphism of the PARP pseudogene on chromosome 13 is not associated with the development of breast cancer in our study population; (b) oligonucleotide-induced PARP activity may be useful for identifying postmenopausal women at increased risk for breast cancer; and (c) there is a possible functional link between the genotype of the PARP pseudogene and enzyme activation.

A note on the estimation of relative risks of rare genetic susceptibility markers.

The comparison of an incident case series with an incident series of second primary cancers, using either a case-control or follow-up study design, is proposed as an efficient method for evaluating the relative risk of a rare genetic susceptibility marker and its prevalence in the population, and for evaluating gene-environment interactions. The relative efficiency of this design versus a conventional case-control study is highly dependent on the population prevalence of the marker and its relative risk. However, for relatively rare but highly penetrant genes, the relative efficiency can be very high. In an example presented regarding a planned study of the p16 gene and its role in melanoma, a conventional case-control study may require up to 70 times as many subjects to achieve equivalent precision to the study of second primaries. The use of second primary cancers in this way requires assumptions about the validity of the classification of a new tumor as a second primary, the extent to which risk of a second cancer is influenced by treatment of the first cancer, and the nature and extent of surveillance bias. However, the problems of ascertaining a valid series of population controls are avoided. The study of second cancers represents an important and underused tool in molecular and genetic epidemiology.

Effects of dietary supplementation of alpha-tocopherol on plasma glutathione and DNA repair activities.

In a randomized double-blind trial of alpha-tocopherol (vitamin E), we investigated the effects of alpha-tocopherol supplementation on lipid- and water-soluble antioxidants in plasma and DNA repair activities in peripheral mononuclear leukocytes. Baseline levels of antioxidants and DNA repair activities were assessed twice before alpha-tocopherol intervention: on day 1 (visit 1) and day 3 (visit 2). During the second visit, participants were randomized to receive one of three dosages of alpha-tocopherol, 15, 60, or 200 mg/day for 4 weeks. The same biochemical measurements as at baseline were repeated twice after intervention: on day 17 (visit 3) and day 31 (visit 4). A total of 31 healthy volunteers were eligible for the study, completed all four visits and were included in the final data analysis. At baseline, no appreciable differences of dietary intake of vitamin E and plasma alpha-tocopherol were observed among the three dosage groups. In general, supplementation of alpha-tocopherol for 2-4 weeks resulted in a dose-dependent increase of plasma level of alpha-tocopherol (compared to baseline); significant increases of plasma alpha-tocopherol at visits 3 and 4 were observed in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. At visit 4 (but not visit 3), plasma glutathione levels were significantly elevated (compared to baseline) in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. In addition, there was an increase in the lipid protection ratio by supplementation of alpha-tocopherol for 2-4 weeks in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. In general, there were no consistent effects of alpha-tocopherol on DNA repair activities in peripheral mononuclear leukocytes after being adjusted for baseline DNA repair activities. Results from this study demonstrate the interrelationship between alpha-tocopherol and other antioxidants in plasma; total plasma antioxidants can be modulated by short-term dietary supplementation of alpha-tocopherol.

Glutathione S-transferase M1 and susceptibility to nasopharyngeal carcinoma.

Genetic polymorphisms for enzymes that metabolize tobacco smoke have been reported to determine susceptibility to several smoking-related cancers, including cancers of the lung, bladder, and head and neck. Glutathione S-transferase M1 (GSTM1) detoxifies benzo(a)pyrene and other carcinogens in tobacco smoke. Approximately 50% of Caucasians lack the GSTM1 gene. Because the most common type of nasopharyngeal cancer (NPC), squamous cell carcinoma, is related to smoking, we sought to determine whether GSTM1 is associated with risk for NPC. Cases (n = 83) were from a population-based study conducted from 1987 to 1993 at five cancer registries in the United States. Random-digit dialing controls (n = 114) were matched to the cases for age, sex, and registry. Subjects participated in a phone interview and blood draw. Absence of GSTM1 was associated with increased risk for NPC (odds ratio = 1.9, 95% confidence interval = 1.0-3.3 for all cases; and odds ratio = 1.7, 95% confidence interval = 0.8-3.5 for squamous cell cases). This relationship was not modified by smoking history, but stronger relationships between glutathione S-transferase and NPC were suggested among subjects who used alcohol more frequently than others, older subjects (50 or more years of age), and women relative to men. These data indicate that absence of GSTM1 moderately increases risk for NPC and add to growing evidence that GSTM1 is a determinant of risk for several smoking-related cancers.

Associations between human leukocyte antigen type and nasopharyngeal carcinoma in Caucasians in the United States.

A genetic component to nasopharyngeal carcinoma (NPC) has been suggested by associations of the malignancy with human leukocyte antigens (HLAs) in Southern Chinese populations, among which NPC is a major cancer. Data from other races are inconclusive. We have investigated associations between NPC and HLA antigens at the HLA-A, B, C, and DQ loci and alleles at the DRB1 locus in a population-based, multicenter investigation in the United States. Data from 82 cases and 140 controls are presented, making this the largest study population analyzing data from Caucasians to date. HLA frequencies from study cases were also compared with external control groups from the 11th International Histocompatibility Workshop and the National Marrow Donor Program. Logistic regression methods were used to investigate the effects of the joint occurrence of multiple HLA types and to assay for differences in HLA-associated risk in different age groups. A meta-analysis was undertaken to compare and summarize our results with previously published findings. The meta-analysis found a protective association with A2 antigen in non-Chinese [odds ratio (OR), 0.63; P < 0.001], a protective association with A11 across all races (OR, 0.54; P < 0.001), and an increased risk associated with B5 in Caucasians (OR, 2.81; P < 0.001). The present study also found independent associations, in a logistic regression model, between NPC and DRB1*1501 (OR, 0.33), DRB1*0405 (OR, 7.57), and Cw3 (OR, 0.42), although these data must be interpreted cautiously due to multiple-testing considerations. Associations were found to be more pronounced in younger patients for A2, A11, A28, B8, and B51.

Nasopharyngeal cancer in a low-risk population: defining risk factors by histological type.

Nasopharyngeal cancer (NPC) is a major public health problem in parts of Southeast Asia and North Africa, but is rare among whites and blacks. Although infection with the EBV and genetic susceptibility appear to play large roles in high-incidence populations, migrant studies suggest that environmental factors may also be important. Aside from the high risks associated with ingestion of salted fish, surprisingly few other risk factors have been established from studies in endemic areas. We studied a low-incidence population to determine whether tobacco use, alcohol consumption, and certain medical conditions and treatments are related to NPC and to examine variations in risk by histology. We reasoned that new relationships might be best identified in the absence of strong causal pathways, such as intake of preserved foods and genetic susceptibility. A population-based case-control study was conducted from 1987 to 1993 at five cancer registries in the United States: western Washington, metropolitan Detroit, Connecticut, Iowa, and Utah. Controls were identified by random digit dialing and frequency matched to the gender and age distribution of cases at each registry. Telephone interviews were completed by 231 cases and 246 controls. We observed a strong dose-response relationship between cigarette smoking and risk of differentiated squamous cell carcinoma (test for trend, P < .001). The highest risk [odds ratio (OR), 6.5; 95% confidence interval (CI), 2.0-21.3] occurred among current smokers with a history of more than 60 pack-years. In contrast, there was no evidence that undifferentiated or nonkeratinizing carcinomas were associated with cigarette smoking. Similarly, a significant increase in risk was observed for the heaviest alcohol consumers (21 or more drinks/week) only for differentiated squamous cell carcinomas (OR, 2.9; 95% CI, 1.2-6.9). The associations with cigarettes and alcohol appeared to be stronger among persons 50 years or older. There was a suggestion that diagnosis with infectious mononucleosis (a marker of late infection with EBV) is linked with decreased NPC risk (OR, 0.4; 95% CI, 0.1-1.1). This report indicates that over two-thirds of differentiated squamous cell NPC cases arising in older persons in the United States can be accounted for by cigarettes and alcohol, but leaves unexplained cases arising in the young and carcinomas of undifferentiated or nonkeratinizing histology. Future studies of NPC need to take into account histology and age in evaluating these and other environmental and genetic risk factors.

Evaluation of factors associated with skin self-examination.

Early detection and excision of thin lesions may be important in reducing mortality from melanoma. Periodic skin self-examination may be beneficial in identifying thin lesions. The purpose of this study was to evaluate factors associated with skin self-examination. The study population was comprised of 549 Caucasian residents of Connecticut 18 years of age or older who were selected as controls as part of a population-based case-control study on skin self-examination and melanoma conducted during 1987-1989. Personal interviews were conducted to obtain information on skin self-examination, demographics, history of cancer, phenotypic characteristics, sun exposure habits, and screening and health behaviors. Nevus counts were performed by trained nurse interviewers. Logistic regression was used to model the relationship between the variables of interest and skin self-examination. Female gender was identified a priori as a predictor of skin self-examination, and thus all analyses were stratified by gender. Age, education, and marital status were also identified a priori as important predictor variables and were selected for inclusion in the final models. Skin awareness was a strong factor associated with skin self-examination for both females and males. For females, previous benign biopsy or the presence of an abnormal mole was identified as important for future skin self-examination using our criteria. A family history of cancer, physician examination, and change in diet to reduce cancer risk increased the likelihood of skin self-examination in males but not females. In women, light hair color may increase the likelihood of performing skin self-examination. Older age and college or postgraduate education was associated with a decreased likelihood of performing skin self-examination in both males and females. Identifying factors associated with skin self-examination will enable health care providers to target individuals who may not be performing skin self-examination but who are at increased risk for developing melanoma.

Alpha-tocopherol dietary supplement decreases titers of antibody against 5-hydroxymethyl-2'-deoxyuridine (HMdU).

This study evaluated the effects of vitamin E (alpha-tocopherol) on oxidative DNA damage in a randomized double-blind Phase II chemoprevention trial. Oxidative DNA damage was measured by the level of auto-antibody (Ab) against 5-hydroxymethyl-2'-deoxyuridine (HMdU) in plasma. After the baseline screening, eligible subjects (n = 31; plasma samples from 28 subjects were available for this study) were randomized to receive 15, 60, or 200 mg of alpha-tocopherol per day for 28 days. Biomarkers were measured twice at baseline--on day 1 (visit 1) and day 3 (visit 2)--and twice after intervention--on day 17 (visit 3) and day 31 (visit 4). At baseline, there was a highly significant inverse correlation between anti-HMdU Ab titer and plasma vitamin E level (r = -0.53; P = 0.004; n = 28). Smoking did not affect baseline anti-HMdU Ab titer; however, anti-HMdU Ab titer levels at baseline were significantly lower in subjects with above-median (0.75 ounce/day) alcohol consumption (P = 0.008). No significant change in anti-HMdU Ab level occurred at either visit 3 or visit 4 for subjects on the lowest dose, 15 mg alpha-tocopherol per day. Subjects receiving 60 mg of alpha-tocopherol per day had a significant decrease in anti-HMdU Ab level at visits 3 and 4 compared with baseline (P = 0.049 and P = 0.02, respectively). However, subjects receiving the highest dose, 200 mg/day, had less consistent results: a significant decrease in anti-HMdU Ab level was seen at visit 4 (P = 0.04) but not at visit 3. Our results demonstrate an inverse relationship between alpha-tocopherol and anti-HMdU Abs in plasma; oxidative DNA damage can be modulated by short-term dietary supplementation of alpha-tocopherol in some subjects.