Lynch syndrome (Hereditary Nonpolyposis Colorectal Cancer, HNPCC) is the most common hereditary syndrome predisposing to colorectal cancer, accounting for 1-3% of all colorectal cancer. This multi-organ cancer predisposition syndrome is caused by mutations in the mismatch repair (MMR) genes, especially MLH1 and MSH2, and to lesser extents MSH6 and PMS2, which lead to widespread genetic instability and thus microsatellite instability (MSI). Hereditary cancer often manifests in two or more tumours in a single individual; 35-40% of Lynch syndrome patients have synchronous or metachronous tumours of the two major Lynch syndrome-related cancers: colorectal and endometrial. The main purposes of the work underlying this thesis were to identify persons at risk of Lynch syndrome or other types of hereditary colorectal cancer, to estimate the cancer risks associated with these predispositions and to identify the underlying genetic causes. A population-based cohort of 78 persons with double primary colorectal or colorectal and endometrial cancer was identified. Cancer risks in their 649 first-degree relatives were estimated in relation to tumour MSI status (positive or negative) and age at diagnosis (before or after 50 years of age) in the probands. The overall standardised incidence ratio was 1.69 (95% CI; 1.39-2.03). The highest risks for Lynch syndrome-associated cancers: (colorectal, endometrial, ovarian and gastric) were found in families with young MSI-positive probands, likely representing Lynch syndrome families. Importantly, no overall risk was found in families with old probands, irrespective of MSI status. Blood samples were available from 24 MSI-positive patients for mutation screening of MLH1, MSH2 and MSH6. Sequence variants or rearrangements predicted to affect protein function were found in 16 patients. Six novel variants were found: two large rearrangements, two truncating and two missense mutations. The missense mutations were found to segregate in the families. Studies of allele frequencies, MSI and loss of immunostaning in tumours from family members further supports the hypothesis that these missense changes play a role in Lynch syndrome, as do the non-conservative nature and evolutionary conservation of the amino acid exchanges. Five families had mutations in MLH1, five in MSH2, and six in MSH6. The unexpectedly large impact of MSH6 was in genealogical studies shown to be due to a founder effect. Cumulative risk studies showed that the MSH6 families, despite their late age of onset, have a high lifetime risk for all Lynch syndrome-related cancers, significantly higher in women (89% by age 80 years) than in men (69%). The gender differences are in part due to high endometrial (70%) and ovarian cancer risk (33%) in addition to the high colorectal cancer risk (60%). These findings are of great importance for counselling and surveillance of families with MSH6 mutations. Finally, in a large family with MSI-negative hereditary colorectal cancer for which the MMR genes and APC had been excluded as possible causes, a genome-wide linkage analysis was performed, resulting in a suggested linkage to chromosome 7. Conclusions: Relatives of probands with MSI-positive, double primary colorectal and endometrial cancer diagnosed before the age of 50 years have significantly increased risks of Lynch syndrome-related cancers. MSH6 mutations, which have unusually high impact in this study population due to a founder effect, confer high cumulative risks of cancer despite the generally late age of onset.

This thesis examines cancer and mortality rates among people diagnosed with hepatitis B (HBV) and C (HCV) infection in New South Wales (NSW) from 1990 through 2002, by linking hepatitis notifications with the NSW Central Cancer Registry (CCR) and National Death Index. Of the 39101 HBV, 75834 HCV and 2604 HBV/HCV co-infection notifications included 1052, 1761 and 85 were linked to cancer notifications and 1233, 4008 and 186 were linked to death notifications respectively. Of 2072 hepatocellular carcinoma (HCC) notifications to the CCR 323, 267 and 85 were linked to HBV, HCV and HBV/HCV co-infection notifications. Incidence of HCC was 6.5, 4.0 and 5.9 per 1000 person years for HBV, HCV and HBV/HCV co-infected groups. Risk of HCC in those diagnosed with hepatitis was 20 to 30 times greater than the standard population. There was a marginally statistically significant increased risk of immunoproliferative malignancies associated with HCV infection (SIR=5.6 95% CI 1.8 ???17.5). Risk of death for those with hepatitis was significantly greater, 1.5 to 5 fold, than the general population with the greatest risk among those with HBV/HCV co-infection. The primary cause of HBV deaths was liver related, particularly HCC, whereas in the HCV groups drug related deaths were most frequent. Among people with HCV, risk of dying from drug related causes was significantly greater than from liver related causes (p=0.012), with the greatest increased risk in females age 15- 24 years (SMR 56.9, 95%CI 39.2???79.9). Median age at diagnosis of HCC varied markedly by country of birth and hepatitis group: HBV 66, 63 and 57years ; HCV 51, 68 and 71 years; unlinked 69, 70 and 64 years for Australian, European, and Asian-born groups, respectively (P<0.0001 for all groups). While the risk of cancer, particularly HCC, is elevated among people with HBV and HCV infection, the absolute risk remains low. Young people with HCV face a higher mortality risk from continued drug use than from liver damage related to their HCV infection. The influence of IDU in the epidemiology of HCC in New South Wales was possibly reflected in the varying distributions of age and country of birth.

Made available in DSpace on 2016-12-23T13:56:11Z (GMT). No. of bitstreams: 1 Neide Aparecida Tosato Boldrini.pdf: 1554664 bytes, checksum: f1a0fa6f6e19b3d6ef0434edfba4dd67 (MD5) Previous issue date: 2012-04-04 / Introduction: The squamous cell cervical cancer develops from precancerous lesions well defined which can progress to invasive disease if not earlier diagnosed and treated. Objectives: To determine the prevalence and factors associated with high-grade lesions and cervical cancer among women treated at University Hospital in Vitoria, ES. Methods: A cross-section conducted in women 18-59 years who were referred for outpatient cervical pathology in 2011. Women were invited to participate and were interviewed for collecting demographics, epidemiological and clinical data. After the interview, they were submitted to gynecological examination to collect specimens for cervical cytology, Chlamydia trachomatis and HPV Hybrid Capture tests, and HPV DNA detection by PCR and colposcopic examination. The patients with cervical lesions at cytology and colposcopy were confirmed by histopathology. Results: A total of 291 women participated in the study. The median age was 38 years (DIQ: 30 - 48 years), 74 (25.4%) had completed four years of schooling; 178 (61.2%) were married and 83 (28.5%) had monthly family income up to three minimum wages. When considering histopathological results, the prevalence of high-grade lesions/cervical cancer was 18.2% (95% CI: 13.8% -22.6%), being 48 (16.5%) cases of high-grade lesions (CIN II, CIN IIIca in situ) and 5 (1.7%) cases of invasive carcinoma. One hundred and eight women (37.1%) were smokers; 11 (3.8%) reported using illicit drugs;38 (13.1%) reported their first sexual intercourse before age 15;221 (75 9%) had more than one partner in life; 20 (6.9%) had more than one partner in the last 12 months;220 (75.6%) reported not using condoms;90 (30.2%) reported anal sex practice;46 (15.8%) reported previous STD. In the final logistic regression model, age between 30-49 years [OR = 4.4 (95%:1.01-19.04), history of smoking [OR = 2.43 (95% CI 1.14 to 5 , 18)], practice of anal intercourse [OR = 2.35 (95% CI 1.10 to 5.03)] and have a positive hybrid capture test for high risk HPV positive [OR = 11.23 (95% 4 0.79 to 26, 36)] remained independently associated with high-grade lesion/cervical cancer. Conclusions: The results show high prevalence of precursor lesions of cervical cancer and high prevalence of high risk HPV. The most prevalent HPV was HPV 16 followed by HPV 31. Associated risk factors for HSIL/carcinoma were age between 30-49 years, history of smoking, practice of anal sex and have a positive hybrid capture test for high risk HPV positive. The study emphasizes the importance of prevention and care strategies for the control of cervical cancer. / Introdução: O câncer cervical de células escamosas se desenvolve a partir de lesões pré-cancerosas bem definidas, que podem progredir para doença invasiva, se não forem precocemente diagnosticadas e tratadas. Objetivos: Determinar a prevalência e os fatores associados para lesões de alto grau (HSIL) e câncer de colo uterino em mulheres atendidas em Hospital Universitário de Vitória, ES. Métodos: Estudo de corte-transversal conduzido em mulheres de 18 a 59 anos que foram referenciadas para o ambulatório de patologia cervical em 2011. As mulheres foram convidadas a participar do estudo e responderam a uma entrevista contendo dados demográficos, epidemiológicos e clínicos. Após a entrevista foram submetidas ao exame ginecológico para coleta de espécime para citologia cervical, para detecção de HPV e Chlamydia trachomatis por teste de Captura Híbrida, pesquisa de DNA de HPV pela técnica de PCR e exame colposcópico. Os casos que apresentaram lesões cervicais na citologia e colposcopia foram confirmados pelo exame histopatológico. Resultados: um total de 291 mulheres participaram do estudo. A mediana de idade foi de 38 anos (DIQ: 30- 48 anos); 74 (25,4%) tinham até quatro anos de estudo, 178 (61,2%) eram casadas e em 83 (28,5%) a renda familiar era de até três salários mínimos. Quando se considerou o resultado histopatológico, a prevalência de HSIL/câncer cervical foi de 18,2% (IC95%:13,8%-22,6%), sendo 48 (16,5%) casos de lesão de alto grau (NIC II,NIC IIIca in situ) e 5 (1,7%) casos de carcinoma invasor. Cento e oito mulheres (37,1%) eram fumantes, 11 (3,8%) informaram usar drogas ilícitas; 38 (13,1%) tiveram o primeiro coito antes dos 15 anos; 221 (75,9%) tiveram mais de um parceiro na vida; 20 (6,9%) tiveram mais de um parceiro nos últimos 12 meses; 220 (75,6%) relataram não usar preservativos; 90 (30,2%) referiram ter pratica de sexual anal; 46 (15,8%) DST prévia. No modelo final de regressão logística, ter idade entre 30-49 anos [OR=4,4 (IC95%:1,01-19,04); história de tabagismo [OR=2,43 (IC95% 1,14-5,18)]; a prática de coito anal [OR=2,35 (IC95% 1,10-5,03)] e ter teste de captura híbrida para HPV de alto risco positivo [OR=11,23 (IC95% 4,79-26,36)] permaneceram independentemente associados à lesão de alto grau/câncer cervical. Conclusões: Os resultados mostram alta prevalência de lesões precursoras de carcinoma cervical e alta prevalência de HPV de alto risco. O HPV mais prevalente foi o HPV 16, seguido do HPV 31. Os fatores de risco associados à HSIL/carcinoma foram ter idade entre 30 e 49 anos, ser tabagista, relatar prática de coito anal e ter resultado positivo para HPV de alto risco. O estudo enfatiza a importância das estratégias de prevenção e assistência para o controle do câncer cervical.

Made available in DSpace on 2014-06-11T19:35:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-25Bitstream added on 2014-06-13T18:46:16Z : No. of bitstreams: 1 silva_fs_dr_araiq.pdf: 2849421 bytes, checksum: 9c4094e5d741a2f65f25f770fedc84be (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / No Brasil, a queima da cana de açúcar é utilizada para facilitar a colheita, mas este procedimento causa grande poluição ambiental devido a quantidade de fuligem lançada na atmosfera. O material particulado (MP) emitido contém inúmeros contaminantes, tais como: hidrocarbonetos policíclicos aromáticos (HPAs) e elementos. A cidade de Araraquara/SP possui cerca de 200.000 habitantes e é cercada por plantações de cana de açúcar, sendo que a prática de queimada é constante no período da safra (abril-novembro, todos os anos). Neste trabalho, determinou-se a concentração elementar e de HPAs em MP na cidade de Araraquara durante o período da safra (S) e da entre safra (E) da cana de açúcar. Foram coletadas 60 amostras (E) e 220 amostras (S) para a análise de HPAs, e 10 amostras (E) e 10 amostras (S) para a análise elementar. As amostras foram coletadas utilizando um amostrador dicotômico (vazão: 10 L min-1, 24 h) com filtros de PTFE (37 mm, 2 μm de tamanho de poro). Para a análise de HPAs, dez filtros de PTFE contendo o MP foram extraídos em banho de ultrassom com acetona/n-hexano (1:1 v/v), sendo que as análises foram efetuadas por HPLC/FLD. A análise elementar foi efetuada por fluorescência de raios X por energia dispersiva (EDXRF), sem tratamento prévio das amostras. A concentração mediana de HPAs totais foi de 1,9 ng m-3 (E) e 6,2 ng m-3 (S). A concentração mediana de benzo[a]pireno, HPA considerado carcinogênico, foi de 0,026 ng m-3 e 0,15 ng m-3 para os períodos de E e S, respectivamente. O risco potencial de câncer associado à exposição a HPAs por inalação, foi estimado com base na concentração de benzo[a]pireno equivalente (BaPeq), onde a toxicidade de uma mistura de HPAs é definida pela concentração de cada substância multiplicada pelo seu fator de equivalência de toxicidade relativa (FET). Os valores medianos encontrados para... / In Brazil, the sugar cane crops are burned to facilitate the harvesting, this procedure causes environmental pollution from the large amounts of soot that are released into the atmosphere. This particulate matter (MP) contains numerous contaminants such as polycyclic aromatic hydrocarbons (PAHs) and metals. The city of Araraquara, located at central area from São Paulo State, has around 200,000 inhabitants and is surrounded by sugarcane plantations (46,994 ha of total cultivated area, in the harvest 2008/2009). In this study, PAHs concentrations and elemental composition in the MP were determined in Araraquara city during the sugarcane harvesting (HV) and non-harvesting (NHV) seasons. 60 samples were collected during the NHV and 220 samples during the HV seasons for the analysis of PAHs. 10 samples were collected during the NHV and 10 samples during the HV season for the analysis of Si, K, Ca, Ti, V, Fe, Sr, Cr, Ni, Mn, Cu, Zn, As, Cd, Pb, Sb, Al, S and Cl. The samples were collected using a dichotomous sampler (10 L min-1, 24 h) with PTFE filters. Ten filters sets were extracted (ultrasonic bath with hexane/acetone (1:1 v/v)) and analyzed by HPLC/FLD for the analysis of PAHs. Information concerning the bulk elemental concentration was provided by energy-dispersive x-ray fluorescence (EDXRF). The median concentration for total PAHs was 1.9 ng m-3 (NHV) and 6.2 ng m-3 (HV). Benzo[a]pyrene median concentration was 0.026 ng m-3 and 0.15 ng m-3 for the NHV and HV seasons, respectively. The potential cancer risk associated to inhalation exposure was estimated based on the benzo[a]pyrene toxic equivalence (BaPeq), where the overall toxicity of a PAH mixture is defined by the concentration of each compound multiplied... (Complete abstract click electronic access below)

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Many medical devices have been shifting to personal platforms such as smartphones due to its ubiquitous availability, variety of included sensors, robust communication, and user-friendliness. By utilizing smartphones as a medical sensing device should improve the early detection of abnormalities and the long-term monitoring of health conditions. Tissue abnormalities will be detected by touch sensation due to mechanical property changes within the tissue. However, touch sensation is unquantifiable and subjective. We integrate the smartphone with a tactile sensor to build a portable and personalized tissue assessment device based on changes in mechanical properties. The Smartphone Tactile Imaging Probe (STIP) is developed to quantify the mechanical properties of the tissue. The proposed system has a dual-sensing mode: compression-based sensing (STIP-C) and indentation-based sensing (STIP-I). STIP–C is designed to detect and measure the size and hardness of the inclusion. It assesses mechanical property changes caused by the tumor inside the tissue. STIP–I is designed to measure the pitting parameters and viscoelastic properties of the tissue. This system will assess the viscoelasticity changes caused by fluid retention within the tissue. STIP estimates mechanical and viscoelastic behavior changes in the tissue and provides the risk evaluation of an underlying health problem. Breast cancer risk assessment and edema severity level classification are the main applications of STIP. We estimate the breast cancer risk by incorporating the patient’s personal risk value into the STIP-C data associated with the tumor mechanical properties to improve the risk assessment accuracy. To classify the edema severity level, the STIP-I measures the pitting parameters and viscoelastic properties of the tissue. From these parameters, we build a Viscoelastic Pitting Recovery (VPR) model. The model illustrates the changes in tissue viscoelastic behavior associated with the edema severity level. Using the VPR model, we use the thresholding method to classify the edema cases. We also developed customized phantoms representing the different amounts of fluid retention in the tissue. The experimental result found a relationship between the amounts of pitted depth from STIP-I and the fluid amount of a phantom. In this dissertation, we developed and tested a portable tissue mechanical property estimation system. The interchangeable dual-mode STIP sensing probe and risk assessment methods were developed for the breast tumor malignancy and edema severity applications. / Electrical and Computer Engineering

In light of health disparities involving African Americans having disproportionately high rates of obesity, type II diabetes, cancer risk, heart disease and hypertension, the study was conducted with an all-Black adult sample (n= 470). Some 53.0% were female and the sample had a mean age of 32 years. The study evaluated the Knowledge of Physical Activity and Dietary Intake Guidelines Survey (KOPA-DIGS-40) as a new True-False knowledge test—with all True items. The study found moderately high levels of knowledge using the KOPA-DIGS-40. Findings using paired t-tests found evidence that ratings for (1) knowledge of guidelines and (2) self-efficacy for adherence to guidelines were significantly higher after taking the test. The study found noteworthy predictors of a higher KOPA-DIGS-40 score to be older age, higher education, and higher Body Mass Index. The study focused on three time periods (1-before the COVID-19 pandemic, 2-during the pandemic, 3-currently) and ratings on four health dimensions (1-physical health, 2-mental/emotional health, 3-physical activity level, 4-eating a healthy diet). Findings showed declines on the four dimensions during the pandemic, yet by Spring 2023 there were significant improvements—with a return by Spring 2023 to pre-pandemic levels. Findings suggested evidence of resilience after experiencing the stress of a global pandemic. Thus, a resilience theory and framework may be vital in guiding a future era of health disparities research with African Americans. Further, the study found an increase in social support during the pandemic, which continued into their current lives. Future research should continue to utilize the innovation of the genre of research reflected in this study’s use of the new Knowledge of Physical Activity and Dietary Intake Guidelines Survey (KOPA-DIGS-40)—as a True-False test with all True items; this follows from evidence the KOPA-DIGS-40 served as a brief online e-health intervention associated with increases in (1) knowledge of the guidelines and (2) self-efficacy for adherence to physical activity and dietary intake guidelines. Given the high rates of obesity, type II diabetes, cancer risk, heart disease and hypertension for African Americans, the findings make an important contribution to the literature—while suggesting future directions in research and interventions.

Lynch syndrome (LS), Lynch-like syndrome (LLS) and familial colorectal cancer type X (FCCX) are different entities of familial cancer predisposition leading to an increased risk of colorectal cancer (CRC). The aim of this prospective study was to characterise and to compare the risks for adenoma and CRC in these three risk groups. Data was taken from the registry of the German Consortium for Familial Intestinal Cancer. Patients were prospectively followed up in an intensified colonoscopic surveillance programme that included annual examinations. Cumulative risks for adenoma and CRC were calculated separately for LS, LLS and FCCX, and then for males and females. Multivariate Cox regression was used to analyse the independent contributions of risk group, mismatch repair gene (within LS), sex and previous adenoma. The study population comprised 1448 individuals (103 FCCX, 481 LLS and 864 LS). The risks were similar for colorectal adenomas, but different for first and metachronous CRC between the three risk groups. CRC risk was highest in LS, followed by LLS and lowest in FCCX. Male sex and a prevalent adenoma in the index colonoscopy were associated with a higher risk for incident adenoma and CRC. In patients with LS, CRC risks were particularly higher in female MSH2 than MLH1 carriers. Our study may support the development of risk-adapted surveillance policies in LS, LLS and FCCX. What's new? While associations between colorectal cancer (CRC) risk and Lynch syndrome (LS) are well-described, less is known about CRC risks linked to the closely related Lynch-like syndrome (LLS) and familial colorectal cancer type X (FCCX). In this prospective follow-up study of patients with LS, LLS, and FCCX, risks were similar for colorectal adenomas but considerably different for first and metachronous CRCs. In addition, LS females who carried MSH2 mutations had notably higher CRC risks than female MLH1 mutation carriers. The identification of variations in carcinogenic pathways between LS, LLS, and FCCX could enable risk-adapted CRC surveillance for these syndromes.

Chiu Yuk Lan. / "December 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 160-185) / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Radiation from Computed Tomography (CT) is now the major contributor to population radiation dose. Despite controversy around the dose-effect relationship of radiation from CT, the linear non-threshold (LNT) theory is endorsed by many authorities, and constitutes the basis of cancer risk estimates. The purpose of this study was (1) a literature review of radiobiological theories, and methods of dose saving stategies in CT; (2) to highlight the importance of dose saving in CT, and to demonstrate how dose can be saved in a radiology department: Following a 40% reduction in reference X-ray tube current for a CT of the urinary tract, the effecitve dose and estimated lifetime attributable risk of incident cancer due to this CT in a group (n=103) were reduced by 37% and 38% in an age and sex-matched group respectively. The literature review showed that the public health implications of CT radiation exposure remain uncertain. / Health Studies / M.A. (Public Health)