Keratinocyte carcinoma

Keratinocyte carcinoma is by far the most common cancer in the United States. Basal cell carcinomas and squamous cell carcinomas account for approximately 80% and 20% of cases of KC, respectively. The term nonmelanoma skin cancer is commonly used to refer to squamous cell carcinomas and basal cell carcinomas; however, other types of nonmelanoma skin cancer, such as adnexal tumors and sarcomas, are less common and differ in their cell type, behavior, and epidemiologic features from KC. Primary care clinicians are well positioned to diagnose KC and to educate patients about preventive measures such as sun protection and self-examination. Here we review epidemiologic data and strategies for prevention, diagnosis, and clinical management of KC.     

Genetic predictors of adverse radiotherapy effects: the Gene-PARE project

PURPOSE: The development of adverse effects resulting from the radiotherapy of cancer limits the use of this treatment modality. The validation of a test capable of predicting which patients would be most likely to develop adverse responses to radiation treatment, based on the possession of specific genetic variants, would therefore be of value. The purpose of the Genetic Predictors of Adverse Radiotherapy Effects (Gene-PARE) project is to help achieve this goal. METHODS AND MATERIALS: A continuously expanding biorepository has been created consisting of frozen lymphocytes and DNA isolated from patients treated with radiotherapy. In conjunction with this biorepository, a database is maintained with detailed clinical information pertaining to diagnosis, treatment, and outcome. The DNA samples are screened using denaturing high performance liquid chromatography (DHPLC) and the Surveyor nuclease assay for variants in ATM, TGFB1, XRCC1, XRCC3, SOD2, and hHR21. It is anticipated that additional genes that control the biologic response to radiation will be screened in future work. RESULTS: Evidence has been obtained that possession of variants in genes, the products of which play a role in radiation response, is predictive for the development of adverse effects after radiotherapy. CONCLUSIONS: It is anticipated that the Gene-PARE project will yield information that will allow radiation oncologists to use genetic data to optimize treatment on an individual basis.     

Lycopene in the prevention of prostate cancer

Based on the evidence from epidemiologic, animal, and in vitro data and human clinical trials, it is evident that lycopene, a non-provitamin A carotenoid, is a promising agent for prostate cancer chemoprevention. It is also clear that the form of lycopene used (purified versus food sources), dose of lycopene and concomitant use with other carotenoids and antioxidants, duration of exposure, specific target populations, and stage of disease appear to play a major role in determining agonistic or antagonistic effects. Based on our review, there is enough evidence to warrant use of lycopene in phase I and II clinical trials to examine its safety and efficacy as a potential chemopreventive agent for prostate cancer. The objective of this article is to review this evidence from epidemiologic, animal, in vitro, and clinical trials and provide the need and rationale to examine further the role of lycopene for prostate cancer prevention.     

Isolation of a group at risk for stomach cancer based on genetic and epidemiological study data

The predictive value of risk factors of stomach cancer was studied on the basis of the results of a complex genetico-epidemiologic survey conducted with a view to identifying the group at risk. An optimal combination of these factors and the multifactor method of mathematical statistics were used in working out a decision instruction. Application of the latter offers an 80% credibility in selecting persons at high risk for stomach cancer development. The paper deals with the findings on a significant relationship between stomach cancer development and genetic and familial factors as well as on indications at certain changes in gastrointestinal function observed before clinical manifestation of the disease. The results point to the efficacy of complex clinical, genetic and epidemiologic studies conducted for prediction of neoplasms caused by a set of factors.     

Role of Aspirin in Breast Cancer Survival

Chemotherapy and hormonal therapy have significantly decreased breast cancer mortality, although with considerable side effects and financial costs. In the USA, over three million women are living after a breast cancer diagnosis and are eager for new treatments that are low in toxicity and cost. Multiple observational studies have reported improved breast cancer survival with regular aspirin use. Furthermore, pooled data from five large randomized trials of aspirin for cardiovascular disease showed that subjects on aspirin had decreased risk of cancer mortality and decreased risk of metastatic cancer. Although the potential mechanism for aspirin preventing breast cancer is not known, possible pathways may involve platelets, inflammation, cyclooxygenase (COX) 2, hormones, or PI3 kinase. This review article summarizes the current epidemiologic and clinical trial evidence as well as possible underlying mechanisms that justify current phase III randomized trials of aspirin to improve breast cancer survival.     

Risk of lung cancer from environmental exposures to tobacco smoke

Epidemiologic evidence on the relation between environmental tobacco smoke and cancer is reviewed. The labeling of tobacco smoke as an environmental cause of lung cancer has been challenged based on allegations of bias in the epidemiologic data. However, tobacco smoke has been shown to increase the risk of lung cancer down to the lowest exposure levels. Environmental tobacco smoke contains the same carcinogenic compounds as those found in the tobacco smoke inhaled directly by the smoker. Nonsmokers environmentally exposed have elevated levels of tobacco smoke byproducts in biological samples. These observations alone are sufficient to identify tobacco smoke as an environmental carcinogen. The epidemiologic studies showing that environmental exposure to tobacco smoke is associated weakly but consistently with increased risk of lung cancer. While these epidemiologic studies have been challenged, it does not appear that the observed epidemiologic associations are due to misclassification or confounding. Indeed, the epidemiologic results, particularly among the studies with superior data collection methods and better control of bias and confounding, find consistent associations between environmental tobacco smoke and lung cancer. This paper summarizes the evidence that environmental exposure to tobacco smoke increases the risk of lung cancer, and considers the criticisms of the epidemiologic evidence which have been raised.     

Update on epidermal growth factor receptor mutations in non-small cell lung cancer.

In 2004, several investigators reported that somatic mutations in the epidermal growth factor receptor gene were associated with clinical responses to erlotinib and gefitinib in patients with non-small cell lung cancer. Since then, multiple groups have examined the biological properties that such mutations confer as well as the clinical relevance of these mutations in patients with non-small cell lung cancer. Although a tremendous amount of knowledge has been gained in the past 2 years, there remain a number of important epidemiologic, biological, and clinical questions.     

Clinical and Molecular Characteristics and Burden of Kidney Cancer Among Hispanics and Native Americans: Steps Toward Precision Medicine

Cancer disparities in Native Americans (NAs) and Hispanic Americans (HAs) vary significantly in terms of cancer incidence and mortality rates across geographic regions. This review reports that kidney and renal pelvis cancers are unevenly affecting HAs and NAs compared to European Americans of non-Hispanic origin, and that currently there is significant need for improved data and reporting to be able to advance toward genomic-based precision medicine for the assessment of such cancers in these medically underserved populations. More specifically, in states along the US-Mexico border, HAs and NAs have higher kidney cancer incidence rates as well as a higher prevalence of kidney cancer risk factors, including obesity and chronic kidney disease. They are also more likely to receive suboptimal care compared to European Americans. Furthermore, they are underrepresented in epidemiologic, clinical, and molecular genomic studies of kidney cancer. Therefore, we maintain that progress in precision medicine for kidney cancer care requires an understanding of various factors among HAs and NAs, including the real kidney cancer burden, variations in clinical care, issues related to access to care, and specific clinical and molecular characteristics.     

Krebspr?vention durch Lebensstil – was ist evidenzbasiert?

Thousands of epidemiologic studies, in addition to clinical trials and basic scientific research create a convincing picture of the current potential for cancer prevention: at least 50% of all cancers could be prevented through a healthy lifestyle. The most important risk factors are smoking, incorrect nutrition and overweight or obesity, as well as lack of physical activity. Cancer risk can be reduced by quitting smoking and sunscreen use, higher intake of plant-based foods, regular physical activity, aspirin use, HPV immunization and use of cancer screening. It is noteworthy to consider that for each type of cancer different risk and preventive factors exist; thus, data need to be interpreted appropriately to develop sound public health recommendations.     

分子流行病学的原理与应用及对人前列腺癌的研究

癌瘤形成是一个涉及瘤的起始、促进、转变、演进和建成的多阶段过程。与人癌危险（ｃａｎｃｅｒｒｉｓｋ）有关的致癌因子，有的已知，有的尚不清楚，包括遗传易感性，以及职业的、环境的、和生活方式等因子。可疑致癌因子与癌危险之间的联系通常是用经典流行病学方法来研究，就是将受到暴露的一组人群与年龄性别配对与未受到暴露的对照组比较。即使用此法证实有联系，但仍得不到其中的因果关系。况且，经典流行病学技术用以估计个体的癌危险，其应用性是有限的。分子流行病学是一新兴领域，着重于用分子遗传学和生化技术来评估个体的癌危险。它能在临床症状发生前，就能用生物学标志来鉴定癌危险，行施有效的干预。从体内外实验模型，综合基因结构、功能和异常的知识，并建立一系列与分子的和遗传的损伤，以及与瘤诊断和预后测定有关的生物学标志，分子流行病学潜在地帮助人们获知人类健康和疾病的更高认识，从而可更适当地推论到更大的人群中去。本文试图用概念图式介绍关键方法，来阐明这些原理，并提供如何用特定的研究技术来探讨前列腺细胞转化和癌变的问题。     

Teaching epidemiology and biostatistics through interactive problem solving

Medical education should prepare students for the reasoning and decision making that are required in a physician's clinical work. The disciplines of epidemiology and biostatistics, as combined in clinical epidemiology, lend themselves very well to this purpose. A lecture course in epidemiology and biostatistics was redesigned to emphasize interactive learning through problem-solving workshops in which students worked with actual data from two epidemiologic studies. A third workshop provided experience in the critical appraisal of an epidemiologic study from the current literature. Students respond favorably to these active learning experiences, which deal with relevant contemporary health problems. The concepts of clinical epidemiology should be integrated into clinical teaching in all stages of training.     

The need for epidemiologic studies of in-situ carcinoma of the breast

Summary The purpose of this paper is to present background information on carcinoma in situ (CIS) of the breast and to provide a theoretical framework for planning epidemiologic studies which may further our understanding of breast cancer. Two types of epidemiologic studies are needed which incorporate CIS of the breast: (i) case-control studies, in which in-situ lesions serve as disease outcomes (endpoints), and (ii) cohort studies and clinical trials, in which diagnosis of in-situ carcinoma serves as a starting point for patient treatment and follow-up. Case-control studies focusing on the causes of CIS have distinct advantages: if risk factors for cancer contribute to pathways involving some intermediate stages but not others (e.g. comedo-type but not non-comedo-type DCIS; LCIS versus DCIS), the use of precursor lesions may more clearly reveal risk factor associations than studies of invasive breast cancer alone; epidemiologic studies of precursor lesions are conducted closer in time to the exposures suspected to be causes and may reduce recall bias or other forms of misclassification; genetic alterations in early lesions are more likely to represent causal events in development of the malignant phenotype. Population-based case-control studies of CIS may thus prove useful in understanding breast cancer etiology and designing preventive strategies. CIS patients identified for case-control studies may be followed up over time as a cohort. Cohort studies (and clinical trials) of CIS aim to elucidate mechanisms influencing progression of CIS to invasive cancer as well as to evaluate effectiveness of specific treatment modalities. Although the majority of CIS lesions of the breast are ductal carcinoma in situ (DCIS), epidemiologic studies which also include patients with lobular carcinoma in situ (LCIS) address potential differences between DCIS and LCIS with respect to both etiology and progression.     

Human papillomavirus-associated head and neck squamous cell carcinoma: mounting evidence for an etiologic role for human papillomavirus in a subset of head and neck cancers

There is increasing molecular and epidemiologic evidence that human papillomavirus (HPV) is associated with a distinct subset of head and neck squamous cell carcinomas. The strength and consistency of HPV DNA presence in oropharyngeal cancers bolster the argument that this association is likely causal. HPV-positive tonsillar cancer in particular is emerging as a specific disease entity with distinct molecular, pathologic, and clinical characteristics. Recent data suggest that the incidence of tonsillar carcinoma in the United States is increasing, despite a decline in tobacco use, supporting the existence of other important risk factors such as HPV infection. Individuals with a history of an HPV-associated anogenital cancer and HIV-infected men are at increased risk for tonsillar carcinoma. This review focuses on the recent literature (since 1998) investigating the relationship between HPV and head and neck cancer development, using the current paradigm for causal inference in epidemiologic research attributed to Sir A. Bradford Hill. Data examining the association of HPV with pathogenesis of head and neck squamous cell carcinoma before 1999 were previously reviewed in this journal.     

The Health Examinees (HEXA) Study: Rationale,Study Design and Baseline Characteristics

Background: Korea has experienced rapid economic development in a very short period of time. A mixtureof traditional and modern risk factors coexists and the rapid change in non-genetic factors interacts withgenetic constituents. With consideration of these unique aspects of Korean society, a large-scale genomic cohortstudy-the Health Examinees (HEXA) Study-has been conducted to investigate epidemiologic characteristics,genomic features, and gene-environment interactions of major chronic diseases including cancer in the Koreanpopulation. Materials and Methods: Following a standardized study protocol, the subjects were prospectivelyrecruited from 38 health examination centers and training hospitals throughout the country. An interviewbasedquestionnaire survey was conducted to collect information on socio-demographic characteristics, medicalhistory, medication usage, family history, lifestyle factors, diet, physical activity, and reproductive factors forwomen. Various biological specimens (i.e., plasma, serum, buffy coat, blood cells, genomic DNA, and urine) werecollected for biorepository according to the standardized protocol. Skilled medical staff also performed physicalexaminations. Results: Between 2004 and 2013, a total of 167,169 subjects aged 40–69 years were recruited forthe HEXA study. Participants are being followed up utilizing active and passive methods. The first wave of activefollow-up began in 2012 and it will be continued until 2015. The principal purpose of passive follow-up is basedon data linkages with the National Death Certificate, the National Cancer Registry, and the National HealthInsurance Claim data. Conclusions: The HEXA study will render an opportunity to investigate biomarkers ofearly health index and the chronological changes associated with chronic diseases.     

Interactions Between Cytotoxic Chemotherapy and Antiretroviral Treatment in Human Immunodeficiency Virus-Infected Patients with Lung Cancer

Interactions between combination antiretroviral therapy (CART) and lung cancer treatment are emerging clinical concerns. Among the reasons for that, one can observe the longer survival of human immunodeficiency virus (HIV)-infected patients since introduction of CART and the epidemiologic rising of lung cancer, mainly adenocarcinomas, in this population. In addition, the higher relative risk of lung cancer in HIV-infected patients compared with general population has been recently demonstrated. Patients' demography and disease characteristics differ from the general lung cancer population, although most cases occur in patients with a smoking history: HIV-infected subjects are generally younger and diagnosis frequently made at locally advanced or metastatic stages. The choice of cytotoxic chemotherapy and antiretroviral therapy is essential in the context of lung cancer (1) to minimize potential interactions and life-threatening toxicities particularly through cytochrome P450 interaction, (2) to implement adequate prevention of foreseeable toxicity, and (3) to fully reinforce antineoplastic and antiretroviral efficacy. Pharmacokinetics data and clinical cases pinpoint to potential life-threatening interactions between protease inhibitors/ritonavir and taxanes, vinca alkaloids, as well as the anilinoquinazolines erlotinib and gefitinib and irinotecan. Optimal choice of chemotherapy and CART in HIV-infected patients with lung cancer is an individualized multidisciplinary decision, involving clinical and antiretroviral history, and predicting potential adverse events and interactions.     

Risk models used to counsel women for breast and ovarian cancer: a guide for clinicians

Advances in the identification and treatment of breast and ovarian cancer have lead to a need for reliable estimates of susceptibility risk associated with these two cancers. These estimates may be used in clinical settings to identify individuals at increased risk of developing disease or of being a carrier of a disease susceptibility allele. Accurate assessment of these probabilities is important given the potential implications for medical decision-making including the identification of patients who might benefit from preventive measures, genetic counseling or from entry into clinical trials. A wide range of empirical and statistical models has been proposed, particularly for breast cancer risk prediction, including those that utilize logistic regression or Bayesian modeling. The specific data used to create the various risk models also varies and may include molecular, epidemiologic, or clinical information. This overview presents definitions of risk used in clinical oncology as well as several of the more frequently used methods of risk estimation for breast and ovarian cancer. In addition, the means by which different methods are able to provide a measure of error or uncertainty associated with a given risk estimate will be discussed.     

An informatics supported web-based data annotation and query tool to expedite translational research for head and neck malignancies

Background  

The Specialized Program of Research Excellence (SPORE) in Head and Neck Cancer neoplasm virtual biorepository is a bioinformatics-supported system to incorporate data from various clinical, pathological, and molecular systems into a single architecture based on a set of common data elements (CDEs) that provides semantic and syntactic interoperability of data sets.     

Barriers and Strategies to Participation in Tissue Research Among African-American Men

Before the burgeoning field of biospecimen collection can advance prevention and treatment methods, researchers must access diverse molecular data samples. However, minorities, especially African-American men, remain reticent to join these studies. This study, using theory-based approaches, investigated African-American men’s barriers to participating in biorepository research. Fourteen focus groups were conducted among 70 African-American men (ages 40 to 80). The groups were stratified by prostate cancer history and educational attainment background. Participants identified perceived factors that promoted or hindered study participation when questioned about their knowledge and attitudes about biospecimen research. Ninety-four percent of participants indicated never participating in a study that collected biological samples. Barriers to their participation included lack of knowledge and understanding regarding biospecimen research practices and uses. In addition, they extensively cited a prevalent mistrust of the medical community and discomfort with study recruitment practices. African-American males were more willing to participate in biorepository studies with physician endorsement or if they understood that participation could benefit future generations. Men also wanted more recruitment and advertising done in familiar places.     

Transition of a clinical trial into translational research: the prostate cancer prevention trial experience

Large clinical trials provide a tremendous opportunity to integrate correlative, comprehensive biological studies with invaluable repositories of biospecimens and clinical and other data from the trial. The Prostate Cancer Prevention Trial (PCPT) was a phase III randomized, double-blind, placebo-controlled clinical trial of finasteride in 18,882 men. Clinical data and blood and tissue specimens were collected at baseline and throughout the study, offering an opportunity to create a program project to investigate hypotheses related to the biology underlying the PCPT findings as well as the etiology and risk of prostate cancer. The transition of the randomized PCPT into this translational and epidemiologic scientific investigation required extensive planning and coordination. Five individual but interrelated projects were brought together with the underlying program theme of the genetic, metabolic, and environmental factors associated with the risks of overall and high-grade prostate cancer and how these factors affected the efficacy of finasteride in preventing cancer. All projects with serum-based measures use a single, shared, nested case-control sample of participants so that each subject provides a more complete biomarker and genetic profile for the evaluation of joint effects of these factors. Strengths of this program include the following: 1) the control group contains only men who are negative for biopsy-detected cancer, 2) the statistical methods to evaluate associations of risk factors with disease are shared across all projects, 3) the large number of cancer cases with fully characterized genetic, metabolic, and behavioral exposures, 4) a central pathology core histopathologically classified the prostate cancer, and 5) cancer cases identified during the PCPT reflect the characteristics of cases currently being detected in the prostate-specific antigen screening era, leading to contemporary and highly relevant results. This article describes the comprehensive methodology and multidisciplinary collaborations, both national and international, essential to a major risk-modeling research program. We provide a framework for doing collaborative research in an international setting structured around a common theme of a clinical trial.