A nested case-control study of radiation exposure and brain cancer incidence in the United States Air Force

A nested case-control study design was used to investigate the relationship between radiation exposure and brain cancer risk in the United States Air Force (USAF). The cohort consisted of approximately 880,000 men with at least 1 year of service between 1970 and 1989. Two hundred and thirty cases were identified from hospital discharge records with a diagnosis of primary malignant brain tumor (International Classification of Diseases, 9th revision, code 191). Four controls were exactly matched with each case on year of age and race using incidence density sampling. Potential career summary extremely low frequency (ELF) and microwave-radiofrequency (MWRF) radiation exposures were based upon the duration in each occupation and an intensity score assigned by an expert panel. Ionizing radiation (IR) exposures were obtained from personal dosimetry records.^ Relative to the unexposed, the overall age-race adjusted odds ratio (OR) for ELF exposure was 1.39, 95 percent confidence interval (CI) 1.03-1.88. A dose-response was not evident. The same was true for MWRF, although the OR = 1.59, with 95 percent CI 1.18-2.16. Excess risk was not found for IR exposure (OR = 0.66, 45 percent CI 0.26-1.72).^ Increasing socioeconomic status (SES), as identified by military pay grade, was associated with elevated brain tumor risk (officer vs. enlisted personnel age-race adjusted OR = 2.11, 95 percent CI 1.98-3.01, and senior officers vs. all others age-race adjusted OR = 3.30, 95 percent CI 2.0-5.46). SES proved to be an important confounder of the brain tumor risk associated with ELF and MWRF exposure. For ELF, the age-race-SES adjusted OR = 1.28, 95 percent CI 0.94-1.74, and for MWRF, the age-race-SES adjusted OR = 1.39, 95 percent CI 1.01-1.90.^ These results indicate that employment in Air Force occupations with potential electromagnetic field exposures is weakly, though not significantly, associated with increased risk for brain tumors. SES appeared to be the most consistent brain tumor risk factor in the USAF cohort. Other investigators have suggested that an association between brain tumor risk and SES may arise from differential access to medical care. However, in the USAF cohort health care is universally available. This study suggests that some factor other than access to medical care must underlie the association between SES and brain tumor risk. ^

Incidence of breast cancer in first-degree female relatives of men with newly diagnosed prostate cancer

Prostate cancer is the most common incident cancer and the second leading cause of death in men in the United States. Although numerous attempts have been made to identify risk factors associated with prostate cancer, the results have been inconsistent and conflicting. The only established risk factors are age and ethnicity. A positive family history of prostate cancer has also been shown to increase the risk two- to three-fold among close relatives.^ There are several similarities between breast and prostate cancer that make the relationship between the two of interest. (1) Histologically, both cancers are predominantly adenocarcinomas, (2) both organs have a sexual and/or reproductive role, (3) both cancers occur in hormone-responsive tissue, (4) therapy often consists of hormonal manipulation, (5) worldwide distribution patterns of prostate and breast cancer are positively correlated.^ A family history study was conducted to evaluate the aggregation of prostate cancer and co-aggregation of breast cancer in 149 patients referred to The University of Texas, M.D. Anderson Cancer Center with newly diagnosed prostate cancer. All patients were white, less than 75 years of age at diagnosis and permanent residents of the United States. Through a personal interview with the proband, family histories were collected on 1,128 first-degree relatives. Cancer diagnoses were verified through medical records or death certificate. Standardized incidence ratios were calculated using a computer program by Monson incorporating data from Connecticut Tumor Registry.^ In this study, familial aggregation of prostate cancer was verified only among the brothers, not among fathers. Although a statistically significant excess of breast cancer was not found, the increased point estimates in mothers, sisters and daughters are consistent with a co-aggregation hypothesis. Rather surprising was the finding of a seven-fold increased risk of prostate cancer and a three-fold increased risk of breast cancer among siblings in the presence of a maternal history of any cancer. Larger family history studies including high risk (African-Americans) and lower-risk groups (Hispanics) and incorporating molecular genetic evaluations should be conducted to determine if genetic differences play a role in the differential incidence rates across ethnic groups. ^

Ethnicity as a risk factor for diabetes incidence in a population of diagnosed hypertensives

Significant racial/ethnic differences exist in prevalence of hypertension (HTN) and non-insulin dependent diabetes mellitus (NIDDM). Hypertension is more common in diabetics than in non-diabetics, and an etiologic link between the two conditions has been proposed. Since there are few longitudinal studies of persons with both HTN and NIDDM, a retrospective cohort study was conducted to determine if ethnicity (Black, Hispanic (Mexican-American), and non-Hispanic White) was related to NIDDM incidence in a low-SES, multi-ethnic clinic population of diagnosed hypertensives. Two thousand nine hundred forty-one hypertensives free of NIDDM at baseline were followed for up to 10 years. Mean baseline age was 56 $\pm$ 12 years, M:F percent was 33:67, and Black:Hispanic:White percent was 63:17:20. There were 236 incident cases of NIDDM. In Cox proportional hazards analysis, the risk of developing NIDDM over 10 years was not related to ethnicity after controlling for significant covariates, including age, baseline blood glucose and body mass index (adjusted RR for Blacks compared to Whites =.82, 95 percent CI =.57-1.18; adjusted RR for Hispanics compared to Whites =.84, 95 percent CI =.51-1.38). This result contrasts with the increased risk of NIDDM among Blacks and Hispanics compared to Whites found in the general population. The study suggests that a diagnosis of hypertension equalizes the risk of developing NIDDM among the three ethnic groups. ^

Macular edema in Hispanics with non-insulin dependent diabetes mellitus in Starr County, Texas: Prevalence, incidence and risk factors

This project is based on secondary analyses of data collected in Starr County, Texas from 1981 till 1991 to determine the prevalence, incidence and risk factors for macular edema in Hispanics with non-insulin-dependent diabetes in Starr County, Texas. Two studies were conducted. The first study examined the prevalence of macular edema in this population. Of the 310 diabetics that were included in the study 22 had macular edema. Of these 22 individuals 9 had clinically significant macular edema. Fasting blood glucose was found to be significantly associated with macular edema. For each 10 mg/dl increase in fasting blood glucose there was a 1.07 probability of an increase in the risk of having macular edema. Individuals with fasting blood glucose $\ge$200 mg/dl were found to be more than three times at risk of having macular edema compared to those with fasting blood glucose $<$200 mg/dl.^ In the second study the incidence and the risk factors that could cause macular edema in this Hispanic population were examined. 240 Hispanics with non-insulin-dependent diabetes mellitus and without macular edema were followed for 1223 person-years. During the follow-up period 27 individuals developed macular edema (2.21/100 person-years). High fasting blood glucose and glycosylated hemoglobin were found to be strong and independent risk factors for macular edema. Participants taking insulin were 3.9 times more at risk of developing macular edema compared to those not taking insulin. Systolic blood pressure was significantly related to macular edema, where each 10 mmHg increase in systolic blood pressure was associated with a 1.3 increase in the risk of macular edema.^ In summary, this study suggests that hyperglycemia is the main underlying factor for retinal pathological changes in this diabetic population, and that macular edema probably is not the result of sudden change in the blood glucose level. It also determined that changes in blood pressure, particularly systolic blood pressure, could trigger the development of macular edema.^ Based on the prevalence reported in this study, it is estimated that 35,500 Hispanic diabetics in the US have macular edema. This imposes a major public health challenge particularly in areas with high concentration of Mexican Americans. It also highlights the importance of public health measures directed to Mexican Americans such as health education, improved access to medical care, and periodic and careful ophthalmologic examination by ophthalmologists knowledgeable and experienced in the management of diabetic macular edema. ^

THE INCIDENCE OF PELVIC ENDOMETRIOSIS IN ROCHESTER, MINNESOTA, 1970-1979

The primary objectives of the study were to measure the incidence of pelvic endometriosis among white females of reproductive age (15-49 years) in Rochester, Minnesota, during the period 1970-1979 and to determine the risk of endometriosis by age, marital status, nun status, and educational attainment in this population. An historical prospective design was used. Incident (newly diagnosed) cases were identified from community medical records, and person-years of risk in the study population were estimated from census data.^ Almost two-thirds of the incident cases had surgically verified endometriosis, while the remainder were diagnosed by clinical findings alone. Incidence rates were prepared first with histologically confirmed cases only and then with the successive inclusion of less certain cases: surgically visualized, clinically probable, and clinically possible. On this basis, overall incidence rates were 108.8 to 246.9 newly diagnosed cases per 100,000 person-years. The incidence of pelvic endometriosis was lowest for women 15-19 years of age, increased markedly through age 44, and then declined for women 45-49 years of age. A significantly greater risk of pelvic endometriosis in never married women was detected only when the numerator was limited to histologically confirmed cases. Among never married women 20-49 years of age, no significant difference in the risk of pelvic endometriosis by nun status was detected, but a trend toward a lower incidence in nuns was observed. Women with education beyond high school had a significantly higher incidence of endometriosis than women with less education.^ Cases in the four diagnostic groups differed greatly by age and marital status but were similar with respect to virtually all other characteristics, once age differences were considered. Reproductive history characteristics described included: age of menarche; history of menopause; total pregnancies; ages of first pregnancy, marriage, and sexual intercourse; years from menarche to first intercourse; years of ovulatory cycling; difficulty becoming pregnant; and delay of the first pregnancy by choice. How these characteristics of incident cases differ from those of women free of endometriosis needs to be studied in future research. ^

FEASIBILITY OF CORRELATING INCIDENCE OF DIARRHEA WITH CHARACTERISTICS OF RURAL EGYPTIAN HOUSEHOLDS BY MEANS OF AN ENVIRONMENTAL SURVEY

Few, if any studies, have attempted to identify the specific environmental factors associated with the incidence of diarrheal disease and to rank these by their contribution to the total incidence of diarrheal illness. Potentially those factors with the greatest contribution are the variables on which intervention could be expected to have the greatest impact on the incidence of diarrhea.^ In 317 rural Egyptian households participating in a longitudinal study of diarrheal disease, selected environmental characteristics were observed and recorded on a questionnaire. Characteristics of the environment were classified into seven categories including water usage, proximity of animals to the house, waste management, food preparation area, toilet area, the household structure and hygiene. The variables from each of the seven major groupings most associated with the incidence of diarrhea in infants were selected through the application of stepwise multiple regression. Each area was then ranked by the portion of the incidence of diarrhea in infants that each composite group of area-specific variables alone would explain. The groups of household structure and water usage variables were found to be more associated with the incidence of diarrhea in infants than variables describing the toilet area, proximity to animals or others. It was also found that 24.7% of the total variance in incidence of diarrheal illness was explained by environmental variables. ^

THE RELATIONSHIP BETWEEN SERUM CHOLESTEROL AND CANCER INCIDENCE IN THE POPULATION OF THE HYPERTENSION DETECTION AND FOLLOW-UP PROGRAM

The relationship between serum cholesterol and cancer incidence was investigated in the population of the Hypertension Detection and Follow-up Program (HDFP). The HDFP was a multi-center trial designed to test the effectiveness of a stepped program of medication in reducing mortality associated with hypertension. Over 10,000 participants, ages 30-69, were followed with clinic and home visits for a minimum of five years. Cancer incidence was ascertained from existing study documents, which included hospitalization records, autopsy reports and death certificates. During the five years of follow-up, 286 new cancer cases were documented. The distribution of sites and total number of cases were similar to those predicted using rates from the Third National Cancer Survey. A non-fasting baseline serum cholesterol level was available for most participants. Age, sex, and race specific five-year cancer incidence rates were computed for each cholesterol quartile. Rates were also computed by smoking status, education status, and percent ideal weight quartiles. In addition, these and other factors were investigated with the use of the multiple logistic model.^ For all cancers combined, a significant inverse relationship existed between baseline serum cholesterol levels and cancer incidence. Previously documented associations between smoking, education and cancer were also demonstrated but did not account for the relationship between serum cholesterol and cancer. The relationship was more evident in males than females but this was felt to represent the different distribution of occurrence of specific cancer sites in the two sexes. The inverse relationship existed for all specific sites investigated (except breast) although a level of statistical significance was reached only for prostate carcinoma. Analyses after exclusion of cases diagnosed during the first two years of follow-up still yielded an inverse relationship. Life table analysis indicated that competing risks during the period of follow-up did not account for the existence of an inverse relationship. It is concluded that a weak inverse relationship does exist between serum cholesterol for many but not all cancer sites. This relationship is not due to confounding by other known cancer risk factors, competing risks or persons entering the study with undiagnosed cancer. Not enough information is available at the present time to determine whether this relationship is causal and further research is suggested. ^

The incidence of necrotizing changes in adults with pneumococcal pneumonia

Background. Necrotizing pneumonia is generally considered a rare complication of pneumococcal pneumonia in adults. We systematically studied the incidence of necrotizing changes in adult patients with pneumococcal pneumonia, and examined the severity of infection, the role of causative serotype and the association with bacteremia. ^ Methods. We used a data base of all pneumococcal infections identified at our medical center between 2000 and 2010. Original readings of chest X-rays (CXR) and computerized tomography (CT) were noted. All images were then reread independently by 2 radiologists. The severity of disease was assessed using the SMART-COP scoring system. ^ Results. There were 351 cases of pneumococcal pneumonia. Necrosis was reported in no original CXR readings and 6 of 136 (4.4%) CTs. With re-reading, 8 of 351 (2.3%) CXR and 15 of 136 (11.0%) CT had necrotizing changes. Overall, these changes were found in 23 of 351 (6.6%, 95% CI 4.0 - 9.1) patients. The incidence of bacteremia and the admitting SMART-COP scores were similar in patients with and without necrosis (P=1.00 and P=0.32, respectively). Type 3 pneumococcus was more commonly isolated from patients with than from patients without necrotizing pneumonia (P=0.05), but a total of 10 serotypes were identified among 16 cases in which the organism was available for typing. ^ Conclusions. Necrotizing changes in the lungs were seen in 6.6% (95% CI 4.0 - 9.1) of a large series of adults with pneumococcal pneumonia. Patients with necrosis were not more likely to have bacteremia or more severe disease. Type 3 pneumococcus was commonly implicated, but 9 other serotypes were also identified.^

Effect of smoking on the association between periodontitis and incidence of coronary heart disease: The Atherosclerosis Risk in Communities Study

Multiple studies have shown an association between periodontitis and coronary heart disease due to the chronic inflammatory nature of periodontitis. Also, studies have indicated similar risk factors and patho-physiologic mechanisms for periodontitis and CHD. Among these factors, smoking has been the most discussed common risk factor and some studies suggested the periodontitis - CHD association to be largely a result of confounding due to smoking or inadequate adjustment for it. We conducted a secondary data analysis of the Dental ARIC Study, an ancillary study to the ARIC Study, to evaluate the effect of smoking on the periodontitis - CHD association using three periodontitis classifications namely, BGI, AAP-CDC, and Dental-ARIC classification (Beck et al 2001). We also compared these results with edentulous ARIC participants. Using Cox proportional hazard models, we found that the individuals with the most severe form of periodontitis in each of the three classifications (BGI: HR = 1.56, 95%CI: 1.15 – 2.13; AAP-CDC: HR = 1.42, 95%CI: 1.13 – 1.79; and Dental-ARIC: HR = 1.49, 95%CI: 1.22 – 1.83) were at a significantly higher risk of incident CHD in the unadjusted models; whereas only BGI-P3 showed statistically significant increased risk in the smoking adjusted models (HR = 1.43, 95%CI: 1.04 – 1.96). However none of the categories in any of the classifications showed significant association when a list of traditional CHD risk factors was introduced into the models. On the other hand, edentulous participants showed significant results when compared to the dentate ARIC participants in the crude (HR = 1.56, 95%CI: 1.34 – 1.82); smoking adjusted (HR = 1.39, 95%CI: 1.18 – 1.64) age, race and sex adjusted (HR = 1.52, 95%CI: 1.30 – 1.77); and ARIC traditional risk factors (except smoking) adjusted (HR = 1.27, 95%CI: 1.02 – 1.57) models. Also, the risk remained significantly higher even when smoking was introduced in the age, sex and race adjusted model (HR = 1.38, 95%CI: 1.17 – 1.63). Smoking did not reduce the hazard ratio by more than 8% when it was included in any of the Cox models. ^ This is the first study to include the three most recent case definitions of periodontitis simultaneously while looking at its association with incident coronary heart disease. We found smoking to be partially confounding the periodontitis and coronary heart disease association and edentulism to be significantly associated with incident CHD even after adjusting for smoking and the ARIC traditional risk factors. The difference in the three periodontitis classifications was not found to be statistical significant when they were tested for equality of the area under their ROC curves but this should not be confused with their clinical significance.^

Incidence of enteric bacterial infections complicating Clostridium difficile infection (CDI)

The purpose of this study was to assess whether C. difficile infection (CDI) increases the risk of bacteremia or E. coli infection. The first specific aim of this study was to study the incidence of post C. difficile bacteremia in CDI patients stratified by disease severity vs. controls. The second specific aim was to study the incidence of post C. difficile E. coli infection from normally sterile sites stratified by disease severity vs. controls. This was a retrospective case case control study. The cases came from an ongoing prospective cohort study of CDI. Case group 1 were patients with mild to moderate CDI. Case group 2 were patients who had severe CDI. Controls were hospitalized patients given broad spectrum antibiotics that did not develop CDI. Controls were matched by age (±10 years) and duration of hospital visit (±1 week). 191 cases were selected from the cohort study and 191 controls were matched to the cases. Patients were followed up to 60 days after the initial diagnosis of CDI and assessed for bacteremia and E. coli infections. The Zar score was used to determine the severity of the CDI. Stata 11 was used to run all analyses. ^ The risk of non staphylococcal bacteremia after diagnosis of CDI was higher compared to controls (14% and 7% respectively, OR: 2.27; 95% CI:1.07-5.01, p=0.028). The risk of getting an E.coli infection was higher in cases than in controls (13% and 9% respectively although the results were not statistically significant (OR:1.4; 95% CI:0.38-5.59;p=0.32). Rates of non-staphylococcal bacteremia and E. coli infection did not differ cased on CDI severity. ^ This study showed that the risk of developing non-staphylococcus bacteremia was higher in patients with CDI compared to matched controls. The findings supported the hypothesis that CDI increases the risk of bacterial translocation specifically leading to the development of bacteremia.^

Socioeconomic disparities in thyroid cancer incidence within the Surveillance, Epidemiology, and End Results (SEER) registry, 1980--2008

Background. In the past two decades, the incidence of thyroid cancer in the United States (US) has been increasing. There has been debate on whether the increase is real or an artifact of improved diagnostic scrutiny. Methods. We linked SEER9 database with 2000 US Census to obtain county-level SES (Socioeconomic Status) and compared thyroid cancer incidence trends between high and low SES counties. Joinpoint analysis was used to assess the thyroid cancer incidence trends. Annual Percentage Changes (APCs) were calculated to evaluate incidence trends. Results . The thyroid cancer incidence in high SES counties increased moderately (APC1=+2.5*, *P<0.05) before late 1990s and dramatically increased (APC2=+6.3*) after late 1990s, whereas incidence in low SES counties increased moderately (APC=+3.5*) during the entire time period (1980–2008). For smaller tumors (≤4cm), the APCs in high and low SES counties are similar to each other before late 1990s, but the incidence in high SES counties increased dramatically after late 1990s while that in low SES counties continued at a moderate increase. For large tumors (>4cm), the incidence trends in high SES counties are similar to those of low SES counties, which had a steady moderate increase. Conclusion. Our findings indicate that enhanced detection likely contributed to the increased thyroid cancer incidence in the past decades but cannot fully explain the increase, suggesting that a true increase also exists. Efforts should be made on identifying the cause of this observed increased incidence as well as more refined/selected screening and prevention measures.^

Venous thromboembolism in patients with acute leukemia: Prevalence, incidence, recurrence of thrombosis, risk factors, and impact on survival

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third most preventable cardiovascular disease and a growing public health problem in the United States. The incidence of VTE remains high with an annual estimate of more than 600,000 symptomatic events. DVT affects an estimated 2 million American each year with a death toll of 300,000 persons per year from DVT-related PE. Leukemia patients are at high risk for both hemorrhage and thrombosis; however, little is known about thrombosis among acute leukemia patients. The ultimate goal of this dissertation was to obtain deep understanding of thrombotic issue among acute leukemia patients. The dissertation was presented in a format of three papers. First paper mainly looked at distribution and risk factors associated with development of VTE among patients with acute leukemia prior to leukemia treatment. Second paper looked at incidence, risk factors, and impact of VTE on survival of patients with acute lymphoblastic leukemia during treatment. Third paper looked at recurrence and risk factors for VTE recurrence among acute leukemia patients with an initial episode of VTE. Descriptive statistics, Chi-squared or Fisher's exact test, median test, Mann-Whitney test, logistic regression analysis, Nonparametric Estimation Kaplan-Meier with a log-rank test or Cox model were used when appropriate. Results from analyses indicated that acute leukemia patients had a high prevalence, incidence, and recurrent rate of VTE. Prior history of VTE, obesity, older age, low platelet account, presence of Philadelphia positive ALL, use of oral contraceptives or hormone replacement therapy, presence of malignancies, and co-morbidities may place leukemia patients at an increased risk for VTE development or recurrence. Interestingly, development of VTE was not associated with a higher risk of death among hospitalized acute leukemia patients.^

Pediatric asthma incidence in Texas and associations with ambient ozone levels in an urban area an analysis using Medicaid claims data

Few recent estimates of childhood asthma incidence exist in the literature, although the importance of incidence surveillance for understanding asthma risk factors has been recognized. Asthma prevalence, morbidity and mortality reports have repeatedly shown that low-income children are disproportionately impacted by the disease. The aim of this study was to demonstrate the utility of Medicaid claims data for providing statewide estimates of asthma incidence. Medicaid Analytic Extract (MAX) data for Texas children ages 0-17 enrolled in Medicaid between 2004 and 2007 were used to estimate incidence overall and by age group, gender, race and county of residence. A 13+ month period of continuous enrollment was required in order to distinguish incident from prevalent cases identified in the claims data. Age-adjusted incidence of asthma was 4.26/100 person-years during 2005-2007, higher than reported in other populations. Incidence rates decreased with age, were higher for males than females, differed by race, and tended to be higher in rural than urban areas. With this study, we were able to demonstrate the utility of MAX data for estimating asthma incidence, and create a dataset of incident cases to use in further analysis. ^ In subsequent analyses, we investigated a possible association between ambient air pollutants and incident asthma among Medicaid-enrolled children in Harris County Texas between 2005 and 2007. This population is at high risk for asthma, and living in an area with historically poor air quality. We used a time-stratified case-crossover design and conditional logistic regression to calculate odds ratios, adjusted for weather variables and aeroallergens, to assess the effect of increases in ozone, NO2 and PM2.5 concentrations on risk of developing asthma. Our results show that a 10 ppb increase in ozone was significantly associated with asthma during the warm season (May-October), with the strongest effect seen when a 6-day cumulative lag period was used to compute the exposure metric (OR=1.05, 95% CI, 1.02–1.08). Similar results were seen for NO2 and PM 2.5 (OR=1.07, 95% CI, 1.03–1.11 and OR=1.12, 95% CI, 1.03–1.22, respectively). PM2.5 also had significant effects in the cold season (November-April), 5-day cumulative lag: OR=1.11, 95% CI, 1.00–1.22. When compared with children in the lowest quartile of O3 exposure, the risk for children in the highest quartile was 20% higher. This study indicates that these pollutants are associated with newly-diagnosed childhood asthma in this low-income urban population, particularly during the summer months. ^

Using spatial linear models with SAR and CAR structure to examine Texas lung cancer incidence rates

Scholars have found that socioeconomic status was one of the key factors that influenced early-stage lung cancer incidence rates in a variety of regions. This thesis examined the association between median household income and lung cancer incidence rates in Texas counties. A total of 254 individual counties in Texas with corresponding lung cancer incidence rates from 2004 to 2008 and median household incomes in 2006 were collected from the National Cancer Institute Surveillance System. A simple linear model and spatial linear models with two structures, Simultaneous Autoregressive Structure (SAR) and Conditional Autoregressive Structure (CAR), were used to link median household income and lung cancer incidence rates in Texas. The residuals of the spatial linear models were analyzed with Moran's I and Geary's C statistics, and the statistical results were used to detect similar lung cancer incidence rate clusters and disease patterns in Texas.^

Investigation of the mechanism of increased melanoma incidence in UV -irradiated mouse skin

The availability of transplantable, syngeneic murine melanomas made it possible to study the potential effects of UV radiation on the growth and progression of melanomas in an animal model. The purpose of my study was to determine how UV-irradiation increases the incidence of melanoma out-growth, when syngeneic melanoma cells are transplanted into a UV-irradiated site. Short term intermittent UVB exposure produces a transitory change in the mice which allows the increased outgrowth of melanoma cells injected into the UV-irradiated site. One possible mechanism is an immunomodulatory effect of UVR on the host. An alternative mechanism to account for the increased tumor incidence in the UV-irradiated site, is the release of inflammatory mediators from UV-irradiated epidermal cells. A third possibility is that UVR could induce the production and/or release of melanoma-specific growth factors resulting in increased melanoma outgrowth.^ My first step in distinguishing among these different possible mechanisms was to characterize further the conditions leading to increased development of melanoma cells in UV-irradiated mouse skin. Next, I attempted to determine which of the 3 proposed mechanisms was most likely. To do this, I defined the specificity of the effect by examining the growth of additional C3H tumorigenic cell lines in UV-irradiated skin. Second, I determined the immunogenicity of these tumor cell lines. The tumor cell lines exhibiting increased tumor incidence are restricted to those tumor cell lines which are immunogenic in normal C3H mice. Third, I determined the effect of UVR on melanoma development did not occur in immunosuppressed mice.^ Because of results from these three lines of investigation suggested that the effect was immunologically mediated, I then investigated whether specific immune reactions were affected by local UV irradiation. To accomplish this, I investigated the effect of UVR on cutaneous immune cells and on induction of contact hypersensitivity (CHS), and I also determined the effect of UVR on the development and the expression of systemic immunity against the melanoma cells. There is no clear cut relationship between the number of Langerhans or Thy1+ cells and the UV effect on tumor incidence. Furthermore, there was no suppression of CHS in the UV-irradiated mice. While the development of systemic immunity is significantly reduced, it appears to be sufficient to provide in vivo immunity to tumor challenge. However the elicitation of tumor immunity in immunized mice can be abrogated if tumor challenge occurs in the site of UV irradiation. This investigation provides new information on an effect of UVR on the elicitation of tumor immunity. Furthermore, it indicates that UV radiation can play a role in the development of melanoma other than just in the transformation of melanocytes. ^