Search

Aside from nonmelanoma skin cancers, breast cancer is the most frequent cancer in Western European and North American women. In these countries, breast cancer accounts for about 4% of all deaths, 20% of all cancer deaths, and 25% of all cancer cases in women. The cross-sectional age-specific pattern in Western high-risk populations has revealed a bimodal curve, which has evoked speculation that breast cancer may be associated with two distinctive pathogenic mechanisms. The clinical manifestations of a malignant neoplasm obscure recognition that symptomatic cancer is the phenotypic endpoint of a sequence of molecular and biochemical events occurring over an induction-latency period measured in years. D. E. Anderson observed that familial risk among first-degree relatives of breast cancer patients varied in relation to age at diagnosis (premenopausal vs. postmenopausal) and laterality (unilateral vs. bilateral) in the index patients. Family history also may have an important effect on the probability of developing a second primary cancer in the opposite breast.

Background Tomasetti and Vogelstein have hypothesized that the patterns of cancer incidence in various cells and tissues are highly correlated with the estimated lifetime number of stem cell divisions. The authors reviewed the risks in tissues of 17 types of cancer from the United States and 69 additional countries. Positive correlations were observed consistently between the tissue − specific cancer incidence and the estimated lifetime number of stem cell divisions. The authors concluded that approximately two-thirds of global cancer incidence may be attributed to random DNA replication errors. Methods An epidemiologic perspective is presented that may serve as a counterpoint in interpreting organ-specific cancer risks. The unifying nature of the Tomasetti/Vogelstein hypothesis must be viewed in the context of diverse and contrasting global trends and patterns of types and “causes” of cancers that are closely linked with economic development and cultural lifestyle practices. The presentation is organized by reviewing the global burden of cancer; concepts of causal inferences and counterfactual assumptions; multifactorial causes of hepatocellular carcinoma and a hierarchy of causes that varies internationally; tobacco carcinogenesis and the multiplex associations with 19 cancer sites and tissues; profile in contrasts in transit through the small and large intestine. Observations and conclusions It is readily recognized that DNA replication errors and number of stem cell divisions may vary in individuals and populations due to external environmental genotoxic chemicals and biologic agents, and internal hormonal and metabolic factors. There is a striking contrast in the risk of adenocarcinoma in the small intestine with that in the large intestine. Tomasetti and Vogelstein indicated that the cumulative number of divisions of stem cells over a lifetime in normal epithelial mucosal cells from colorectal cancer patients was 4 time greater than in the epithelial tissue from patients with adenocarcinoma of the small intestine. Their conclusion would suggest a “seed” and “soil” interaction rather than exclusively the independence of either component. Namely, that the contrasting physiological, biochemical, microbial and immunological features in the lumen and on the mucosal surface of the large intestine, in contrast to that in the small intestine, would foster molecular genetic and epigenetic events that are advantageous to neoplasia in the large intestine.

The small intestine extends 6–7 meters from the gastric pylorus to its insertion into the large intestine. Its mucosal surface contains 90% of the absorptive surface area of the digestive tract. Remarkably, in 2015, only about 3% of digestive system cancers and less than 1% of digestive cancer deaths in the United States were observed in the small intestine. In contrast, approximately 50% of cancers in the digestive tract were diagnosed in the large intestine, which measures just 1.5 meters in length. Cancers of the small intestine are among the most heterogeneous of gastrointestinal neoplasms, encompassing pathologic subtypes of neuroendocrine carcinoid, adenocarcinoma, lymphoma, and gastrointestinal stromal tumors. Adenocarcinoma accounted for ~25% to–35% of cancers in the small intestine, in contrast to over 90% of cancers in the large intestine. Genetic syndromes, such as familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC), predispose to adenocarcinoma in the small intestine.

This Introduction provides a broad overview of the scientific advances and crosscutting developments that increasingly influence epidemiologic research on the causes and prevention of cancer. High-throughput technologies have identified the molecular “driver” events in tumor tissue that underlie the multistage development of many types of cancer. These somatic (largely acquired) alterations disrupt normal genetic and epigenetic control over cell maintenance, division and survival. Tumor classification is also changing to reflect the genetic and molecular alterations in tumor tissue, as well as the anatomic, morphologic, and histologic phenotype of the cancer. Genome-wide association studies (GWAS) have identified more than 700 germline (inherited) genetic loci associated with susceptibility to various forms of cancer, although the risk estimates for almost all of these are small to modest and their exact location and function remain to identified. Advances in genomic and other “OMIC” technologies are identifying biomarkers that reflect internal exposures, biological processes and intermediate outcomes in large population studies. While research in many of these areas is still in its infancy, mechanistic and molecular assays are increasingly incorporated into etiologic studies and inferences about causation. Other sections of the book discuss the global public health impact of cancer, the growing list of exposures known to affect cancer risk, the epidemiology of over 30 types of cancer by tissue of origin, and preventive interventions that have dramatically reduced the incidence rates of several major cancers.

Primary prevention has enormous potential to reduce the human, social, and economic costs of cancer worldwide. The following sections discuss the development and application of preventive interventions in six broad areas of public health: tobacco control, the prevention of obesity and physical inactivity, prevention of infection-related cancers, protection against excessive exposure to ultraviolet light, preventive drug therapies (chemoprevention), and the regulation of carcinogenic exposures. All of these areas affect multiple types of cancer and massive numbers of people. Different interventions are at varying stages of development. For example, effective, evidence-based approaches have been developed over several decades to reduce tobacco use, prevent chronic infection with hepatitis B virus, protect children from excessive sun exposure, regulate exposures in high-income countries, and reduce breast cancer incidence and recurrence in high-risk women. More recent efforts are seeking to identify upstream measures to prevent excessive weight gain, reduce caloric intake, and increase physical activity.

Although it has been previously reported that patients with inflammatory breast cancer (IBC) experience worse survival than patients with other breast cancer (BC) types, the socioeconomic and ethnic factors leading to this survival difference are not fully understood. The association between county-level percent of persons below the poverty level and BC-specific (BCS) survival for cases diagnosed from 1990 to 2008 in the Surveillance, Epidemiology, and End Results (SEER) database linked to census derived county attributes was examined. A sub-analysis of cases from 2000 to 2008 also examined BCS survival by an index combining percent below poverty and less than high school graduates as well as metropolitan versus non-metropolitan county of residence. The Kaplan-Meier estimator was used to construct survival curves by stage, inflammatory status, and county-level socioeconomic position (SEP). Stage and inflammatory status stratified proportional hazards models, adjusted for age, race/ethnicity, tumor and treatment characteristics were used to determine the hazard of BCS death by county-level SEP. Kaplan-Meier survival curves indicated IBC has worse survival than stage matched non-IBC, (stage III IBC median survival = 4.75 years vs. non-IBC = 13.4 years, p < 0.0001). Residing in a lower SEP, non-metro county significantly worsens BCS survival for non-IBC in multivariate proportional hazards models. African American cases appear to have worse survival than non-Hispanic Whites regardless of inflammatory status, stage, county-level SEP, tumor, or treatment characteristics. This is the first study to examine IBC survival by SEP in a nation-wide population-based tumor registry. As this analysis found generally poorer survival for IBC, regardless of SEP or race/ethnicity, it is important that interventions that help educate women on IBC symptoms target women in various SEP and race/ethnicity groups.

Arsenic is a pervasive contaminant in underground aquifers worldwide, yet documentation of health effects associated with low-to-moderate concentrations (100microg/L) has been stymied by uncertainties in assessing long-term exposure. A critical component of assessing exposure to arsenic in drinking water is the development of models for predicting arsenic concentrations in private well water in the past; however, these models are seldom validated. The objective of this paper is to validate alternative spatial models of arsenic concentrations in private well water in southeastern Michigan.From 1993 to 2002, the Michigan Department of Environmental Quality analyzed arsenic concentrations in water from 6050 private wells. This dataset was used to develop several spatial models of arsenic concentrations in well water: proxy wells based on nearest-neighbor relationships, averages across geographic regions, and geostatistically derived estimates based on spatial correlation and geologic factors. Output from these models was validated using arsenic concentrations measured in 371 private wells from 2003 to 2006.The geostatisical model and nearest-neighbor approach outperformed the models based on geographic averages. The geostatistical model produced the highest degree of correlation using continuous data (Pearson's r=0.61; Spearman's rank rho=0.46) while the nearest-neighbor approach produced the strongest correlation (kappa(weighted)=0.58) using an a priori categorization of arsenic concentrations (5, 5-9.99, 10-19.99,or = 20microg/L). When the maximum contaminant level was used as a cut-off in a two-category classification (10,or =10microg/L), the nearest-neighbor approach and geostatistical model had similar values for sensitivity (0.62-0.63), specificity (0.80), negative predictive value (0.85), positive predictive value (0.53), and percent agreement (75%).This validation study reveals that geostatistical modeling and nearest-neighbor approaches are effective spatial models for predicting arsenic concentrations in private well water. Further validation analyses in other regions are necessary to indicate how widely these findings may be generalized.

Chronic venous disease is a common condition presenting to physicians in Western Europe and the United States. This article provides a comprehensive review of the published literature in the English language, from 1942 to the present, and focuses on the prevalence of chronic venous insufficiency and varicose veins, as well as the involved risk factors. Prevalence estimates vary widely by geographic location, with the highest reported rates in Western countries. Reports of prevalence of chronic venous insufficiency vary from < 1% to 40% in females and from < 1% to 17% in males. Prevalence estimates for varicose veins are higher

Objectives To examine the progression of lower urinary tract symptoms in a longitudinal population-based cohort of black men. Population-based studies of prostatism and longitudinal data regarding changes in lower urinary tract symptom severity have largely focused on white men, with little attention directed toward black men. Methods In 1996, a probability sample of 369 black men, aged 40 to 79 years, residing in Genesee County, Michigan, and without a prior history of prostate cancer/surgery participated in a prostate cancer screening protocol that included completing the American Urological Association Symptom Index (AUASI). Four years after baseline, 175 of the 369 men agreed to participate in the follow-up protocol. Of the 175 men, 149 had not reported undergoing treatment for benign prostatic hyperplasia and had complete symptom data. These men were included in this study. Differences between baseline and follow-up AUASI scores were examined. Results The mean and standard deviation AUASI scores at baseline and follow-up were 7.1 (6.4) and 7.0 (6.8), respectively. Although overall no statistically significant change was found in the mean AUASI during the 4 years of follow-up (−0.11; SD 6.2; P = 0.7), the average change in the symptom score and the variability in the change increased with patient age at baseline from a mean of −0.42 (SD 5.0) among men in their 40s to 2.1 (SD 6.6) among men in their 70s. Of the 91 men (61.1%) who reported mild to no symptoms (AUASI score 7 or less) at baseline, 24 (26.4%) reported moderate to severe symptoms (AUASI score 8 or more) at follow-up. This progression of symptom severity was observed across all ages. Conclusions In this population-based study of longitudinal changes in urinary symptoms in black men, we found a substantial percentage of men demonstrated a measurable progression in urinary symptom severity over time. Additional studies are needed to examine critically any racial differences in lower urinary tract symptom progression.

Even though colorectal cancer (CRC) screening tests for persons 50 years of age or over are recommended to reduce colorectal cancer mortality, screening rates remain disturbingly low.Using random digit dialing, 355 telephone interviews were conducted with black and white men and women, 50-79 years of age, who resided in Genesee County, Michigan. The Health Belief Model provided the framework to assess attitudes and practices regarding CRC screening.For both endoscopic procedures, significantly higher percentages of whites than blacks were aware of the screening procedure (P0.05). Overall, fewer than 30% of respondents were adherent to current CRC screening guidelines. Adherence was lowest for black females: 21% for fecal occult blood test, 20% for flexible sigmoidoscopy, and 12% for colonoscopy. Black males compared to black females were about 2.8 times more likely to have had either flexible sigmoidoscopy or colonoscopy (P0.05). Physician recommendation was a powerful motivator to screening. Two consistent barriers to screening were the belief that: (a) the test is not needed; and (b) the test is embarrassing.Interventions directed at physicians and patients are essential to enhance CRC screening rates. CRC survival rates may be improved by physician-guided promotion of screening that focuses on identified barriers.

Few opportunities exist to evaluate the carcinogenic effects of long-term internal exposure to alpha-particle-emitting radionuclides. Patients injected with Thorotrast (thorium-232) during radiographic procedures, beginning in the 1930s, provide one such valuable opportunity. We evaluated site-specific cancer incidence and mortality among an international cohort of 3,042 patients injected during cerebral angiography with either Thorotrast (n = 1,650) or a nonradioactive agent (n = 1,392) and who survived 2 or more years. Standardized incidence ratios (SIR) for Thorotrast and comparison patients (Denmark and Sweden) were estimated and relative risks (RR), adjusted for population, age and sex, were generated with multivariate statistical modeling. For U.S. patients, comparable procedures were used to estimate standardized mortality ratios (SMR) and RR, representing the first evaluation of long-term, site-specific cancer mortality in this group. Compared with nonexposed patients, significantly increased risks in Thorotrast patients were observed for all incident cancers combined (RR = 3.4, 95% CI 2.9-4.1, n = 480, Denmark and Sweden) and for cancer mortality (RR = 4.0, 95% CI 2.5-6.7, n = 114, U.S.). Approximately 335 incident cancers were above expectation, with large excesses seen for cancers of the liver, bile ducts and gallbladder (55% or 185 excess cancers) and leukemias other than CLL (8% or 26 excess cancers). The RR of all incident cancers increased with time since angiography (P0.001) and was threefold at 40 or more years; significant excesses (SIR = 4.0) persisted for 50 years. Increasing cumulative dose of radiation was associated with an increasing risk of all incident cancers taken together and with cancers of the liver, gallbladder, and peritoneum and other digestive sites; similar findings were observed for U.S. cancer mortality. A marginally significant dose response was observed for the incidence of pancreas cancer (P = 0.05) but not for lung cancer. Our study confirms the relationship between Thorotrast and increased cancer incidence at sites of Thorotrast deposition and suggests a possible association with pancreas cancer. After injection with20 ml Thorotrast, the cumulative excess risk of cancer incidence remained elevated for up to 50 years and approached 97%. Caution is needed in interpreting the excess risks observed for site-specific cancers, however, because of the potential bias associated with the selection of cohort participants, noncomparability with respect to the internal or external comparison groups, and confounding by indication. Nonetheless, the substantial risks associated with liver cancer and leukemia indicate that unique and prolonged exposure to alpha-particle-emitting Thorotrast increased carcinogenic risks.

To determine the magnitude of racial disparity in lower urinary tract symptom (LUTS) severity and bother by combining two large comparable epidemiologic studies of community-dwelling white and black men, thereby avoiding many of the referral biases present in previous studies. Prior studies evaluating racial differences in benign prostatic hyperplasia have been hampered by selection bias, because nearly all have used surgical treatment as a marker for benign prostatic hyperplasia.Data from the Olmsted County Study of Urinary Symptoms and Health Status and the Flint Men's Health Study were combined for a total study sample of 2480 men. We examined LUTS severity and associated bother as measured by the self-administered American Urological Association Symptom Index and Symptom Problem Index.Overall 34% of white men reported moderate/severe LUTS compared with 41% of black men (P0.001). These patterns were consistent across age and persisted after adjustment for age and other sociodemographic factors. The relationship between LUTS severity and bother differed by race in that black men reported less bother for each unit increase in LUTS (P0.001).In contrast to studies based on clinical populations, our community-based study demonstrated greater LUTS severity in black men compared with white men but black men reported less bother for any given level of LUTS severity. Although these findings suggest a racial disparity in benign prostatic hyperplasia, additional studies of anatomic, physiologic, and molecular factors may clarify whether these racial differences are real or due to sociocultural differences in reporting symptom morbidity.

Previous epidemiologic studies evaluating risk factors for lower urinary tract symptoms (LUTS) have focused on White populations. Between September 1996 and January 1998, in a population-based sample of African-American men aged 40-79 years in Flint, Michigan, the authors assessed the role of putative sociodemographic, lifestyle, and medical history risk factors in moderate to severe LUTS, including the subcategories of obstructive and irritative symptoms. After the exclusion of men with prostate cancer or prior prostate surgery and men who were taking alpha-blockers for urinary tract symptoms, 708 participants provided responses to a structured interviewer-administered questionnaire. After multivariable adjustment, current and former smokers were at increased risk of moderate to severe LUTS, including obstructive symptoms. Heavy alcohol consumption and a history of hypertension or diabetes were positively associated with LUTS, and high income (>/=$30,000) was inversely associated with LUTS and with obstructive and irritative symptoms. A history of heart disease was positively associated with LUTS and with irritative symptoms. To the authors' knowledge, this was the first population-based study undertaken in African-American men to evaluate putative risk factors for moderate to severe LUTS, including subcategories of obstructive and irritative urinary symptoms. These results describe associations with specific lifestyle and medical history risk factors.

Exposure to solvents has been reported to increase the risk of scleroderma. The authors investigated the relation between exposures to solvents in occupational and hobby settings and the development of scleroderma among women in a case-control study with population-based controls in Michigan (1980-1991) and Ohio (1980-1992). A total of 660 cases and 2,227 frequency-matched controls were interviewed by telephone. Diagnoses of scleroderma were verified by medical records review. Paint thinners and removers were significantly associated with scleroderma both by self-report (odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.4, 2.6) and after expert review (OR = 2.0, 95% CI: 1.5, 2.6). Other petroleum distillates (gasoline and mineral spirits) were not significantly associated with scleroderma after controlling for other correlated exposures in multivariable analyses. Trichloroethylene was associated with scleroderma both by self-report (OR = 2.0, 95% CI: 0.8, 4.8) and after expert review (OR = 1.9, 95% CI: 0.6, 6.6), but not significantly. Analyses by duration of exposure found that risk increased with the duration of use of any of the solvents (OR = 1.01/year of exposure, 95% CI: 1.01, 1.02), but there was no evidence of increasing risk with increasing duration of exposure for any specific solvent studied. In summary, exposures to paint thinners and removers were associated with scleroderma in women but showed no evidence of increasing risk with increasing duration. Exposures to other specific chlorinated and nonchlorinated hydrocarbon solvents were not clearly associated with scleroderma.

BACKGROUND Previous epidemiologic investigations of the associations of sex-steroid hormones and benign prostatic hyperplasia (BPH) have focused on predominately white populations. The objective of this study was to evaluate potential associations of body mass index (BMI), cigarette smoking, use of alcohol, and endogenous sex-steroid hormones with prostate volume in a population-based sample of African American (AA) men, ages 40–79 yr. METHODS A total of 369 AA men without clinical evidence of prostate cancer were identified in the Flint Men's Health Study by using a population-based sampling procedure. All subjects underwent a complete urologic evaluation that included prostate volume determination by transrectal ultrasonography and serum assays for androgens and estrogens. RESULTS After age adjustment, BMI (weight (kg)/height (m)2) was positively correlated with increasing levels of androstanediol glucuronide (AG), estradiol (E2), estrone sulfate (E1S), and the ratios of E2:total testosterone (TT) and E2:free testosterone (FT); however, increasing BMI was negatively correlated with androstenedione (AD), FT, TT, and sex hormone-binding globulin (SHBG). Multivariable regression models demonstrated that prostate volume increased with age (P

To examine the relationship between insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), and body mass index and prostate volume, as a surrogate marker for benign prostatic hyperplasia, in a community-based sample of black men. Epidemiologic studies examining the role of IGF-1 and IGFBP-3 suggest that increased levels of serum IGF-1 and decreased levels of serum IGFBP-3 are associated with an increased risk of prostate cancer. Few studies have examined these factors with respect to benign prostatic hyperplasia, and these have been limited to white men.The study population consisted of a sample of 364 black men, 40 to 79 years of age, residing in Genesee County, Michigan. Men with prostate cancer or prior prostate surgery were excluded. All subjects completed a clinical examination, which included a complete urologic examination with transrectal ultrasonography, anthropometric measurements, and serum assays for IGF-1 and IGFBP-3.Multivariable regression models demonstrated that prostate volume increased with increasing age (P0.0001) and body mass index (P = 0.03). IGFBP-3 rather than IGF-1 was positively associated with increasing prostate volume (P = 0.003).This is the largest study describing the relationships between IGF-1, IGFBP-3, and body mass index and prostate volume, and the only study in black men. Although earlier studies demonstrated an association between IGF-1 and prostate cancer risk, our findings indicate that IGFBP-3 is more relevant for prostate enlargement, suggesting that IGF-1 and IGFBP-3 may play different pathophysiologic roles in benign and malignant prostatic conditions.

Objectives. To concurrently evaluate urinary obstructive symptoms and incontinence in men after radical prostatectomy and to determine the effects of these components on urinary impairment and satisfaction. Methods. Two hundred twenty-eight men after radical prostatectomy were age-matched and zip code-matched to a random sample of 228 men without prostate cancer. Urinary incontinence was assessed by the urinary function domain of the Prostate Cancer Index, and obstructive symptoms were assessed by the American Urological Association Symptom Index. Regression models were constructed to evaluate the impact of obstructive and incontinence symptoms on urinary impairment and satisfaction. Results. The control group reported greater urinary continence (P

The increased use of prostate-specific antigen (PSA) in screening for preclinical disease after 1985 is thought to be a major determinant of the changing patterns in prostate cancer incidence; however, the long-term effect of screening on future trends in mortality and survival is uncertain. This article reviews the temporal trends (1981-1998) for prostate cancer incidence, mortality, and survival, and projects prostate cancer incidence and mortality rates for 1999 to 2001. Autoregressive, quadratic, time-series models were used to describe prostate cancer mortality rates in the US population and prostate cancer incidence rates derived from the National Cancer Institute's (NCI) Surveillance, Epidemiology and End Results (SEER) program. These models were based on data collected from 1979 through 1998, with forecasts produced for 1999 to 2001. Prostate cancer incidence increased steadily from 1981 to 1989, with a steep increase in the early 1990s, followed by a decline. Incidence rates were forecasted to remain stable through the year 2001. Mortality rates decreased steadily and were forecasted to continue to decrease concurrently with increasing 5- and 10-year relative survival rates. The incidence, mortality, and survival trends were comparable in US blacks, who exhibited on average 2-fold higher mortality and 50% higher incidence than whites. Decreasing prostate cancer mortality and increasing relative survival trends in the United States were described after the introduction of PSA screening. However, the exaggerated rate of increase in the early 1990s in prostate cancer incidence was transient and likely a result of increased detection of preclinical disease that was prevalent in the general population.

The diffusion and frequency of screening may confound demographic comparisons of incidence rates by age, race, ethnicity, socioeconomic status, geographic residence, and temporal trends. Prostate cancer encompasses a biologic spectrum ranging from the commonly prevalent, latent, microscopic, pre-invasive, or minimally invasive form of the disease, which is not apparent clinically, to the substantially diminished fraction, the ‘tip of the iceberg’, that is clinically manifested as invasive and potentially fatal prostate cancer [1]. The accelerated increases in prostate cancer incidence rates in the United States during the late 1980s and early 1990s have been attributed mainly to increased utilization of prostate-specific antigen (PSA)-based screening and the urologic practice of random sextant biopsies based on a PSA threshold in addition to biopsies in suspect areas of digital rectal examination and ultrasound abnormalities [2–5]. Incidence and mortality have decreased since the early 1990s [5]. The introduction of an innovative cancer screening method into the population is associated with enhanced lead-time in diagnosis and expansion of the prevalent pool of diagnosed cases. Alterations in incidence trends may be artifactual and transient, unless there are concurrent factors that are affecting risk in the target population. A challenging aspect of research will be to address whether there are common or contrasting causal factors in the pathogenesis of incipient, latent prostate cancer revealed through screening when compared with clinically apparent disease diagnosed in the absence of screening.

Cervical cancer is an important cause of mortality in women worldwide, and the cervix is a well-established clinical, cytologic, and histopathologic model of carcinogenesis. The cervix is easily accessible for examination and biopsy, and colposcopy improves visualization. Identifying chemopreventives in cervical cancer requires rigorous study design: dose de-escalating phase I, IIa trials; placebo-controlled phase IIb trials; and multicenter phase III trials. Reduction in disease incidence and surrogate endpoint biomarkers (SEB) may be trial endpoints. The goal of chemoprevention studies is to prevent or delay the development of cancer. Each agent requires a phase I or IIa trial for each organ site. Phase I, IIa studies of micronutrients, retinoids, a-difluoromethylornithine, and indole-3-carbinol have demonstrated response rates of up to 70%, but results of placebo-controlled phase IIb studies have been disappointing and their findings confounded by the high regression rates in placebo-treated patients. Enhancement of research methods, including sufficient enrollment guided by power calculations, uniform biopsy at study entry and exit, and strict progression through trial design phases would ensure valid and reliable results. Because human papillomavirus (HPV) is the major etiologic agent, pretrial laboratory and animal studies should have demonstrated the efficacy of the chemopreventive agent to decrease HPV viral protein expression or HPV tumor induction. SEB modulation must be characterized in any trial’s earliest phases before use in phases IIb and III. Lessons learned in chemoprevention will serve as a basis for immunoprevention and vaccine trials.

Purpose: A review of cohort and case-control studies that attempt to quantify the proportion of cancer cases diagnosed in the United States and throughout the world that may be attributed to biologic or infectious agents. Methods: Epidemiologic studies published primarily since the year 2000 are summarized that estimate population attributable fractions based on consensus estimates of relative risk and of the exposure prevalence to putative oncogenic infectious agents in representative populations. Results: The proportion of incident cancers attributable to infectious agents diagnosed in low- and middle-income countries, comprising more than 80% of the world’s population, has been estimated to vary from 20% to 30%, in contrast to a range of 5% or less to 10% in the United States and other highly industrialized populations. More than 90% of the global cancer cases attributed to infectious agents have been caused by hepatitis B virus, hepatitis C virus, human papillomaviruses, and the gram-negative bacterium, Helicobacter pylori. Conclusions: Epidemiologic and pathologic studies that use molecular diagnostic probes and immunologic and biochemical assays have described the substantial impact of infectious agents on global cancer incidence. These compelling observations have stimulated the development of effective hepatitis B virus and human papillomavirus vaccines and the rationale for eradication of Helicobacter pylori.

There are few studies on the long-term sequelae of radionuclides ingested or injected into the human body. Patients exposed to radioactive Thorotrast in the 1930s through the early 1950s provide a singular opportunity, since the administration of this radiographic contrast agent resulted in continuous exposure to alpha particles throughout life at a low dose rate. We evaluated cause-specific mortality among an international cohort of 3,143 patients injected during cerebral angiography with either Thorotrast (n = 1,736) or a similar but nonradioactive agent (n = 1,407) and who survived 2 or more years. Standardized mortality ratios (SMRs) for Thorotrast and comparison patients were calculated, and relative risks (RR), adjusted for population, age and sex, were obtained by multivariate statistical modeling. Most patients were followed until death, with only 94 (5.4%) of the Thorotrast patients known to be alive at the closure of the study. All-cause mortality (n = 1,599 deaths) was significantly elevated among Thorotrast subjects [RR 1.7; 95% confidence interval (CI) 1.5-1.8]. Significantly increased relative risks were found for several categories, including cancer (RR 2.8), benign and unspecified tumors (RR 1.5), benign blood diseases (RR 7.1), and benign liver disorders (RR 6.5). Nonsignificant increases were seen for respiratory disease (RR 1.4) and other types of digestive disease (RR 1.6). The relative risk due to all causes increased steadily after angiography to reach a threefold RR at 40 or more years (P0.001). Excess cancer deaths were observed for each decade after Thorotrast injection, even after 50 years (SMR 8.6; P0.05). Increasing cumulative dose of radiation was directly associated with death due to all causes combined, cancer, respiratory disease, benign liver disease, and other types of digestive disease. Our study confirms the relationship between Thorotrast and increased mortality due to cancer, benign liver disease, and benign hematological disease, and suggests a possible relationship with respiratory disorders and other types of digestive disease. The cumulative excess risk of cancer death remained high up to 50 years after injection with20 ml Thorotrast and approached 50%.

Purpose: Studies of lower urinary tract symptoms in men have been restricted to predominately white populations and these observations may not be generalized to black American men. A goal of the Flint Men’s Health Study was to evaluate the prevalence of lower urinary tract symptoms in a community based sample of black American men.Materials and Methods: We identified 721 eligible subjects after a 2-stage stratified sampling protocol of black American men residing in Flint, Michigan and an in-home interview. Of these men 364 (50%) completed the study protocol, including serum prostate specific antigen measurement, digital rectal examination, uroflowmetry and transrectal ultrasound. These men comprised our study group. Patients completed the American Urological Association (AUA) symptom and bothersomeness scores. Moderate to severe symptoms and impairment were defined as an AUA symptom score of greater than 7 and bothersomeness score of greater than 3, respectively. Data were stratified by 10-year age group...

Objectives. Previous studies have observed higher age-specific serum prostate-specific antigen (PSA) values in African-American (AA) men without prostate cancer compared to white men, leading some to recommend race-specific PSA reference ranges for the early detection of prostate cancer. The primary objective of the Flint Men’s Health Study was to determine age-specific PSA reference values in a community-based sample of AA men, aged 40 to 79 years. Methods. A probability sample of 943 AA men was selected from households in Genesee County, Michigan. Men without a prior history of prostate cancer/surgery were invited to participate in a prostate cancer screening protocol, consisting of measurement of serum total PSA, free/total PSA ratio, and digital rectal examination. Sextant biopsies were recommended, based on total PSA greater than 4.0 ng/mL and/or an abnormal digital rectal examination. Results. From the sample of 943 men, 732 were eligible, 432 had blood drawn for PSA testing, and 374 completed all phases of the clinical examination. The 95th percentile PSA values were estimated to range from 2.36 ng/mL for men in the fifth decade to 5.59 ng/mL for men in the eighth decade. The 95th percentile values for age-specific PSA were comparable to those observed in a similar study of white men in Olmsted County, Minnesota. The median and 5th percentile values for free/total PSA did not vary significantly across age. Conclusions. The minor differences in PSA reference ranges between AA and white men may not be of sufficient magnitude to recommend the use of race-specific PSA reference ranges for screening.

BACKGROUND Surrogate endpoint biomarkers (SEBs) are used as intermediate indicators of a reduction in cancer incidence in chemoprevention studies. SEBs should be expressed differentially in normal and high risk tissue; appear at a well defined stage of carcinogenesis; be studied with reasonable sensitivity, specificity, and accuracy; and be modulated in chemoprevention trials. The concept of SEBs may be useful in the trials of many new therapies. METHODS The current review includes a comprehensive review of the literature. Many SEBs have been the subject of intense study and include quantitative histopathology and cytology, proliferation markers, regulation markers, differentiation markers, general genomic instability markers, and tissue maintenance markers. Because of the critical biologic and epidemiologic role of the human papillomavirus (HPV) in cervical carcinogenesis, the relation between these markers and HPV should be considered. In addition, biomarkers of HPV infection and its regression should be sought. RESULTS Several chemoprevention trials have been published that have included the use of SEBs. The biomarkers that appear most promising in these clinical trials can be measured quantitatively and reproducibly: quantitative histology and cytology, proliferating cell nuclear antigen (PCNA), MIB-1, MPM-2, HPV viral load, epidermal growth factor receptor, polyamines, and ploidy. The markers that have been demonstrated to be modulated in chemoprevention trials in the literature are quantitative histology and cytology, PCNA, MPM-2, HPV viral load, and polyamines. CONCLUSIONS The surrogate endpoint biomarkers of most interest in future research should correlate well with HPV infection, be modulated by several therapeutic agents, and have limited variability and ease in measurement. Cancer 2001;91:1758–76. © 2001 American Cancer Society.

Patients injected with thorotrast, a radiologic contrast medium used from the 1920s to early 1950s, received chronic internal exposure to thorium-232, an alpha-emitter. Epidemiologic studies have observed markedly elevated risks of death from hepatic and hematologic cancers and extensive chromosomal damage among these patients. Few investigations have correlated multiple measures of genetic damage to determine whether these have independent induction kinetics. The distribution of chromosomal aberrations (CA) and mutant frequencies (MF) at the hypoxanthine phosphoribosyltransferase (hprt) locus was evaluated in eight long-term thorotrast survivors (mean exposure time=47.4 years) and five individuals who received a nonradioactive contrast medium during the same era.Peripheral blood lymphocytes were harvested from whole blood, CA were scored in 500 complete metaphases and a clonal assay was used to determine hprt MF. Symmetrical aberrations were not evaluated. Differences in frequencies and correlations between endpoints were assessed using nonparametric methods.Thorotrast-exposed individuals differed from the comparison group in total number of multicentrics and centric and acentric rings (per 500 cells [median, mean +/- sd]: 11, 18.3+/-23.1 vs 2, 2.4+/-1.1, p =0.04). There was no difference between the groups on hprt MF (12.6, 15.9+/-13.5 vs 16.6, 14.0+/-8.8[ x 10(-6)]; p= 1.0). Among the exposed, hprt MF was moderately correlated with the frequency of asymmetrical chromosomal aberrations, although the association was not statistically significant.Noting the limitations of small samples, long-term thorotrast survivors were observed to be at an increased risk for genetic damage.

Objective: To evaluate the accuracy of fluorescence spectroscopy in screening for squamous intraepithelial lesions (SILs) and to compare its performance with that of Papanicolaou smear screening, colposcopy, cervicoscopy, cervicography, and human papillomavirus (HPV) testing. Data Sources: Receiver operating characteristic (ROC) curve analysis was used to analyze performance by fluorescence spectroscopy (primary data) and other methods (secondary data). Methods of Study Selection: In our search, 275 articles were identified in MEDLINE (1966–1996). Articles were included if the investigators had studied a population in whom low disease prevalence was expected; used either Papanicolaou smear screening and colposcopy or colposcopically directed biopsy as a standard against which the screening technique was measured, and included enough data for recalculation of reported sensitivities and specificities. Tabulation, Integration, and Results: Receiver operating characteristic curves for fluorescence spectroscopy were calculated using a Bayesian algorithm, and ROC curves for the other screening methods were constructed using meta-analytic techniques. Areas under the ROC curves and Q points were calculated. Screening colposcopy had the highest area under the curve (0.95), followed by screening cervicography (0.90), HPV testing (0.88), cervicoscopy (0.85), fluorescence spectroscopy (0.76), and Papanicolaou smear screening (0.70). Conclusion: In terms of screening for SILs, fluorescence spectroscopy performed better than the standard technique, Papanicolaou smear screening, and less well than screening colposcopy, cervicography, HPV testing, and cervicoscopy. The promise of this research technique warrants further investigation.

A panel of former presidents of the American College of Epidemiology has been convened to reflect on future challenges in epidemiology and public health and how epidemiologists may be best prepared to meet these challenges. The evolving priorities in the allocation of resources, recruitment and training of health professionals, and the orientation of future intervention programs in disease prevention and control require a global perspective. We cannot afford to view a future that is limited to fulfilling only national priorities. Public health emergencies (e.g., pandemics of infectious diseases) transcend national boundaries and require international collaboration. Another compelling example would be preparedness for bioterrorism, which encompasses the intentional release of bacteria, viruses, or toxins for the purpose of harming or killing civilians (1). The Centers for Disease Control and Prevention (CDC) highlighted ‘‘ten great public health achievements’’ during 1900–1999: vaccines to prevent childhood communicable diseases; measures to ensure motor vehicle safety; establishing guidelines for safety in the workplace; national morbidity and mortality surveillance of acute and chronic diseases; declining coronary heart disease and stroke mortality; increasing safety and nutritional assessment of marketed foods; improving maternal and infant health; assistance in family planning; fluoridation of drinking water; and the recognition of tobacco use as a major health hazard (2). In the latter half of the 20th century, the emergence of chronic diseases provided a stimulus for enhancing the capacity of the public health infrastructure. Epidemiologists, in recognizing the complexity of the etiology and prevention of emerging chronic diseases, developed an increasing capacity for conducting population-based studies that examined health determinants in relationship to molecular and genetic mechanisms as well as social epidemiologic studies that assessed the contextual significance of social class, neighborhood, and ethnicity (3). It is also apparent that the public health infrastructure comprises a partnership of federal, state, and municipal governmental agencies, nongovernmental organizations, academic research and training institutions, and community-based ‘‘stakeholders.’’

BACKGROUND Cancer of the corpus uteri occurs more commonly among white women in the U.S., yet survival is poorer for black women. This study examined whether this trend has changed and also examined the relation of age and histologic subtype to differences in stage. METHODS This retrospective cohort study assessed incidence trends, mortality trends, and the relation of age and histologic subtype to stage for 12,079 incident cases and 2325 deaths registered between 1985 and 1994 in Michigan. Rate ratios compared incidence and mortality. Odds ratios quantified the contribution of age and histologic subtype to differences in risk for advanced stage, using Mantel-Haenszel univariate techniques and multivariate logistic regression. RESULTS The overall incidence rate was 21.99 per 100,000, and the overall mortality rate was 3.82 per 100,000. Black women had a 40% lower risk (rate ratio [RR] = 0.60) of developing cancer of the corpus uteri but had a 54% greater risk (RR = 1.54) of dying from cancer of the corpus uteri. Black women were at greater risk of being diagnosed with either sarcoma or more aggressive adenocarcinoma. However, after adjustment for age and histologic subtype, black women still had an increased risk for advanced stage disease (2.63, 95% confidence interval = 2.19-3.16). CONCLUSIONS The disparity between white and black women persists in incidence and mortality trends for cancer of the corpus uteri. The greater frequency of more aggressive histologic subtypes experienced by black women accounts for only 10% of their excess risk for more advanced stage disease. Cancer 1998;83:1546-1554. © 1998 American Cancer Society.

Objective: To quantify by meta-analysis the performance of colposcopy to set a standard against which new technologies can be compared. Data Sources: MEDLINE was searched for articles on colposcopy for diagnosis of squamous intraepithelial lesions (SIL). The search selected articles from 1960 to 1996 combining the key word “colposcopy” with key words “diagnosis,” “positive predictive value,” “negative predictive value,” “likelihood ratio,” and “receiver operating characteristic (ROC) curve.” Methods of Study Selection: Articles were selected if the authors studied a population of patients with abnormal screening Papanicolaou smears and presented raw data showing for each cervical lesion type the number of patients judged positive and negative by colposcopic impression versus the standard of colposcopic biopsy results. Nine of 86 studies met these criteria. Tabulation, Integration, and Results: Biopsies had been categorized as normal, atypia, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, carcinoma in situ, and invasive cancer; we recalculated performance measures using the Bethesda system. Overall sensitivity, specificity, likelihood ratios, ROC curves, and the corresponding areas under the curves were calculated. The average weighted sensitivity of diagnostic colposcopy for the threshold normal compared with all cervix abnormalities (atypia, low-grade SIL, high-grade SIL, cancer) was 96% and the average weighted specificity 48%. For the threshold normal cervix and low-grade SIL compared with high-grade SIL and cancer, average weighted sensitivity was 85% and average weighted specificity 69%. Likelihood ratios generated small but important changes in probability for distinguishing normal cervix and low-grade SIL from high-grade SIL and cancer. Areas under the ROC curve were 0.80 for the threshold normal cervix compared with all abnormalities and 0.82 for the threshold normal cervix and low-grade SIL compared with high-grade SIL and cancer. Conclusion: Colposcopy compares favorably with other medical diagnostic tests in terms of sensitivity, specificity, and area under the ROC curve. New diagnostic methods for the cervix can be compared with colposcopy using these quantified values.

BACKGROUND Patterns of excess risk for second primary cancers (SPC) in prostate cancer patients have been observed for urinary bladder, other sites in the urinary tract, and hematolymphopoietic tissues in several, but not all, previously reported cohort studies. METHODS The risk of SPC was evaluated in 9,794 Detroit metropolitan-area men originally diagnosed with carcinoma of the prostate during 1973–1982. The cohort was assembled using Detroit Surveillance, Epidemiology, and End Results (SEER) Registry data and followed until December 31, 1993. RESULTS The observed number of SPC of all sites was similar to the expected number in the cohort. A significant excess of invasive SPC of the urinary bladder [Standardized incidence ratio (SIR) = 1.57; 95% CI, 1.34–1.83] was observed in this cohort, but after excluding the first 2 months after prostate cancer diagnosis, the excess (SIR = 1.06) was no longer statistically significant. The cumulative proportion of patients with prostate cancer who developed bladder cancer during a follow-up interval of 20 years was 5.5% (95% CI, 4.1–6.9%). The patients who received first-course radiation treatment were observed to be at increased risk for bladder SPC (all stages; SIR = 1.49; 95% CI, 1.07–2.02) when compared to the Detroit-area male population. CONCLUSIONS These results underscore the importance of continuing medical surveillance for urinary bladder second primary cancers in patients with prostate cancer, but are reassuring in that the magnitude of relative and absolute risks does not suggest deterring adverse effects of radiation treatment or intrinsic risks for neoplasms in other organs or tissues. Prostate 33:75–86, 1997. © 1997 Wiley-Liss, Inc.

OBJECTIVES: This study evaluated a two-step intervention for mammography screening among older women. METHODS: Four hundred and sixty women, identified from physician practices, were randomized to a control or a two-step intervention (physician letter and peer counseling call) group. Women in the intervention group who obtained a mammogram received a grocery coupon. RESULTS: Over the 12 months of the study, more women in the intervention group than in the control group obtained mammograms (38% vs 16%). The most dramatic difference was in the higher odds that women in the intervention group would obtain a mammogram within 2 months (odds ratio = 10.5). CONCLUSIONS: The intervention significantly increased screening mammography. Future efforts must be multifaceted and incorporate the unique concerns of older women.

A case-control study of pancreas cancer in residents, aged 30-79 years, of 18 counties in southeastern Michigan was conducted to investigate the risks of exposure to DDT and related materials in the general population. Sixty-six people with cytologically diagnosed pancreas cancer were identified using 7 participating hospitals in metropolitan Detroit and Ann Arbor. One hundred and thirty-one controls were frequency-matched to the cases on age, sex, ethicity and county of residence by random-digit dialing. All study participants were administered a questionnaire to assess life-time exposure to pesticides from both environmental and occupational sources, family history of cancer, past medical history, smoking history and demographic information. A statistically significant increased risk was found for self-reported exposure to ethylan (1,1-dichloro-2,2-bis(4-methoxyphenyl) ethane). Increased odds ratios were observed for self-reported exposures to chloropropylate and DDT, as well as for the summary group of organochlorine pesticides which included all of these materials, though these associations were not significant.

BACKGROUND Colorectal adenocarcinoma may represent more than one disease process. Numerous epidemiologic studies suggest that rates of occurrence of colorectal adenocarcinoma at particular anatomic subsites (e.g., right colon, left colon, and rectum) may be associated with distinctive geographic, demographic, and risk factor profiles. This study explored time trends over a 22-year period of the incidence of adenocarcinoma of the colon and rectum at various subsites among patients of different race, gender, and stage of disease. METHODS Data on the incidence of colorectal adenocarcinoma were obtained from a population-based cancer registry in the Detroit, Michigan area funded by the National Cancer Institute. Age-adjusted incidence rates were analyzed by year of diagnosis. Relative survival rates were also obtained for different race and gender categories, along with disease stage at diagnosis. RESULTS A major rise was revealed in the incidence of adenocarcinoma in the right colon among African American men and women between the mid-1970s and the early 1980s. The rise was greatest among African American men and accounts for increases in late stage disease among them. Corresponding decreases in survival among African American men were noted. CONCLUSIONS These findings indicated widely differing disease patterns based on anatomic subsite and patient demography and also indicated a need for targeted efforts at early detection of adenocarcinoma of the right colon among African Americans. Cancer 1997; 79:441-7. © 1997 American Cancer Society.

A retrospective cohort study of women with cancers of the lower anogenital tract was derived from the Michigan Tumor Registry records for the years 1985–1992. Incidence rates of invasive cervical, vulvar, vaginal, and anal cancers were analyzed with respect to age, race, year of diagnosis, stage at diagnosis, and histopathology. The incidence of metachronous primary cancers following initial primaries of the cervix was also investigated. Anogenital cancers constituted about 4% of all cancers in Michigan women between 1985 and 1992. Age-adjusted incidence rates per 100,000 women per year for each site were found to be as follows: 10.1 (cervix), 1.9 (vulva), 1.0 (vagina), and 0.6 (anus). The incidence rates of women in the United States for cancers in the anogenital region were higher in blacks than in whites, with the exception of vulvar cancer. U.S. blacks were more likely to develop squamous cell carcinomas, but less likely to develop adenocarcinomas of the cervix and vagina when compared to whites. Over the 5- to 8-year follow-up period, 6.5% of the women with index cases of cervical cancer developed second primary cancers. This represented a 40% increase in the risk of incident primary cancers compared to the risk in the general population of Michigan women. The significant occurrence of second primaries of the vagina following index primaries of the cervix suggests a shared etiology, such as infection with human papillomavirus. The incidences of cancers related to smoking, including cancers of the urinary bladder, lung/bronchus, and lower anogenital tract were also increased.

Our objective is to provide a current perspective on the avoidable causes of global and US cancer incidence and mortality. Cancer registry–based incidence patterns, population behavioral risk-factor survey data, and systematic reviews of epidemiologic studies are the basis for estimates of relative risk, the prevalence of exposures to various lifestyle and environmental risk factors, and their impact expressed as population attributable fractions (PAFs). Of the total 59 million global deaths in 2008, 12–13% were attributed to cancer. The increasing burden of cancers in low- and middle-income countries (LMICs) is attributable in part to increasing urbanization, expansion of the adult population at risk, and increasing or persistent exposures to infectious agents, tobacco, and dietary deficiencies. Attributable fractions for lifestyle and environmental risk factors are summarized for the United States, the United Kingdom, and France. Assuming minimal overlap in the distribution of risk factors in the population and discounting the potential for interaction in their combined effects, we estimate that a maximum of 60% of cancer deaths in the United States may be attributed to eight risk factors: tobacco, alcohol, ionizing and solar radiations, occupations, infectious agents, obesity, and physical inactivity.

The number of adolescent females between the ages of 13 and 19 who are contracting sexually transmitted diseases (STDs) is rising at an alarming rate. Although the issue of STDs has been overshadowed by continued public debate over adolescent pregnancy and childbearing, it demands attention. Particularly concerning is the fact that STDs increase the likelihood of transmitting HIV (N.E. MacDonald et al., 1990). To offset the growing incidences of STDs among female adolescents, gender-specific interventions are needed. Following is a description of the theoretical underpinnings that informed and guided the development of a gender-specific intervention titled Girl Talk. A two-stage creation and review process was used to design this 2.5-hr, four-session intervention. An overview of the quasi-experimental design that compared a nonequivalent comparison and two intervention groups (peer led and adult led) is presented. Baseline characteristics of the three groups are reported. Also described is how participant feedback and a design content analysis are used to evaluate the appropriateness of the intervention for adolescent females.

BACKGROUND The Tecumseh Community Health Study (TCHS), initiated in 1959 at the University of Michigan School of Public Health, has provided a resource for long term prospective studies of the incidence of cancer in the setting of a midwestern rural farming community. METHODS A survey of total and site specific cancer incidence among 7016 male and female adult residents from 1959-1987 was conducted, and the observed number compared with the expected number, based on the age-sex-race-calendar period-and site-specific cancer incidence rates reported by the Connecticut tumor registry. Based on the results of this survey, a hypothesis was advanced concerning the potential risks of exposures to insecticides and herbicides. This was pursued by analyzing for each county in Michigan the comparative annual number of acres and percentage of acreage treated with agricultural chemicals in 1978 and for the period 1982- 1987. Finally, because of the availability of information on lifestyle risk factors that had been collected in the 1960s on all participants, a nested case-control study was implemented. RESULTS The standardized incidence ratio (SIR), based on the observed number divided by the expected number of invasive cancer cases (all sites combined [excluding nonmelanoma skin cancer]), was not significant in females (SIR, 0.95; 95% confidence interval [CI], 0.86-1.05) nor males (SIR, 0.91; 95% CI, 0.81-1.01). A significant increase was demonstrated for males and females combined in the incidence of lymphopoietic neoplasms, namely non-Hodgkin's lymphoma, Hodgkin's disease, and chronic lymphocytic leukemia; the combined SIR was 1.40 (95% CI, 1.03-1.86; P = 0.03). In the Department of Commerce surveys of counties in Michigan, the Tecumseh area (Lenawee County) was ranked highest with respect to the average annual number of acres (240,000 or more) and the percent of acreage (40%) sprayed with herbicides and insecticides. A comparison of temporal trends for cancer incidence since 1973 was reviewed for the Wayne-Oakland-Macomb tricounty area, in which the survey estimated that less than 80,000 acres per year, or less than 8% of acreage, were treated with pesticides. The comparison of the Tecumseh cohort, for all sites combined, was not significantly different from expectation in females (SIR, 1.01; 95% CI, 0.89-1.14), and was decreased by more than 10% in males (SIR, 0.88; 95% CI, 0.77-1.00). However, the SIR for non-Hodgkin's lymphoma in females was significantly elevated (SIR, 1.92; 95% CI, 1.07-3.11, P = 0.02); the trend for increased risks of lymphomas and leukemias was also evident in males. In the nested case-control study, based on risk factor information documented prior to diagnosis, the relative risk of a family history of lymphoma, leukemia, or multiple myeloma was significantly increased among patients with lymphoproliferative neoplasms (odds ratio, 3.81; 95% C1, 1.49-9.79; P = 0.005). CONCLUSIONS This prospective epidemiologic study conducted in a rural farming community in Michigan has found significant increases in the incidence dence of lymphoproliferative cancers. A plausible hypothesis, consistent with the preliminary findings, is that the reported cancer pattern is an expression of risk resulting from sustained environmental exposures to agricultural chemicals, perhaps in conjunction with familial or genetic factors. Cancer 1996; 72763-70. © 1996 American Cancer Society.

This study hypothesized that human papillomavirus (HPV) infection is associated with increased prostate cancer risk, and that the 40% higher incidence rate in blacks is attributable to a greater prevalence of oncogenic viral DNA in prostatic tissues. Viral L1 and E6 gene sequences were polymerase chain reaction (PCR) amplified in archival tissues from 56 prostate cancer cases and 42 hyperplastic controls. L1 amplimers were hybridized by dot blot to HPV L1 generic probes, as were E6 amplimers to E6 probes specific for HPV 6, 11, 16, 18, 31, 33, and 45. 12.5% of cases and 9.5% of controls were HPV positive by L1 hybridization (age/race adjusted odds ratio = 1.66, 95% confidence interval = 0.33, 8.37). Four of 52 (7.7%) blacks were HPV positive compared to 7 of 46 (15.2%) whites. However, none of the L1-positive samples hybridized to the E6 type-specific probes, and positive results were not replicable using a broader spectrum of PCR primers and probes. These data suggest that HPV infection is not a significant risk factor for prostate cancer and does not explain the excess cancer risk in blacks.

‘Department of Epidemiology, School of Public Health, 2Department of Biostatistics, School of Public Health, ‘Division of Rheumatology, Department of Internal Medicine, School of Medicine, 4Division of Rheumatology, Department of Internal Medicine, Wayne State University School of Medicine and %n-vey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI 48109, U.S.A.

Though among U.S. women endometrial cancer is the most common invasive gynecological cancer, it has a relatively favorable prognosis. From 1986-1990, approximately 19% of U.S. Surveillance, Epidemiology and End Results (SEER) Program cases were diagnosed in women less than 55 years of age; however, the age-specific incidence (per 100,000) peaked at 70-74 years (100.7), which was 2.85 times the rate reported at 50-54 years (38.9). The incidence under 50 years was 2.19 times higher in U.S. White compared with U.S. Black women; for uterine corpus cancers diagnosed at 50 years and older, the ratio declined but continued to be elevated in Whites (1.46). In contrast, average annual age-adjusted mortality (per 100,000) from 1986-1990 for uterine corpus cancer (1970 U.S. standard) was almost twice as high in U.S. Black women (6.0) as in U.S. White women (3.3). The determinants of age-specific elevated risks in mortality, in contrast to the lesser age-specific risks in incidence experienced by U.S. Black women compared with U.S. White women, may be explored with respect to socioeconomic and cultural factors that influence the distribution of epidemiologic risk factors such as reproductive history, choice of contraception methods, hormone replacement therapy, obesity, and dietary factors; age-specific prevalence of hysterectomy for other gynecological conditions; quality of medical care and surveillance practices; genetic factors influencing susceptibility; and tumor-associated biological factors. The majority of risk factors and medical conditions associated with endometrial cancer are related directly or indirectly to the levels and metabolic effects of the reproductive hormones, namely estrogens and progestogens. The molecular, genetic and epidemiologic characterization of endometrial cancer is attempting to delineate the multiple steps in the natural history of estrogen-induced or estrogen-responsive neoplasms.