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Zsofia Kote-Jarai,
Edward J Saunders,
Daniel A Leongamornlert,
Malgorzata Tymrakiewicz,
Tokhir Dadaev,
Sarah Jugurnauth-Little,
Helen Ross-Adams,
Ali Amin Al Olama,
Sara Benlloch,
Silvia Halim, [......],
Ed Dicks,
Caroline Baynes,
Don Conroy,
Stig E Bojesen,
Rudolf Kaaks,
Daniel Vincent,
François Bacot,
Daniel C Tessier,
Douglas F Easton,
Rosalind A Eeles
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ABSTRACT: Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.
Human Molecular Genetics 03/2013; · 7.64 Impact Factor
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Rosalind A Eeles,
Ali Amin Al Olama,
Sara Benlloch,
Edward J Saunders,
Daniel A Leongamornlert,
Malgorzata Tymrakiewicz,
Maya Ghoussaini,
Craig Luccarini,
Joe Dennis,
Sarah Jugurnauth-Little, [......],
Sofia Maia,
Paula Paulo,
Ethan Lange,
Kathleen A Cooney,
Antonis C Antoniou,
Daniel Vincent,
François Bacot,
Daniel C Tessier,
Zsofia Kote-Jarai,
Douglas F Easton
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ABSTRACT: Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10(-8)). More than 70 prostate cancer susceptibility loci, explaining ∼30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies.
Nature Genetics 03/2013; 45(4):385-391. · 35.53 Impact Factor
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ABSTRACT: PURPOSE: Few studies have measured dietary changes made among men diagnosed with prostate cancer (PC) without formal dietary interventions, yet they may offer insight into the needs of PC survivors. This study examined dietary changes in men before and after treatment for PC within the prostate testing for cancer and treatment randomized trial. METHODS: This was a prospective cohort study in community-based men aged 50-69 tested for PC in nine UK areas. 3,935 men completed food frequency questionnaires before diagnosis and 678 with localized PC repeated the questionnaire 1 year later (response 82.7 %). RESULTS: Men subsequently diagnosed with or without PC all consumed similar diets before diagnosis. Diagnosis of PC led to dietary changes, with 234 (34.7 %) men eating more fresh tomatoes (p < 0.0001) and 156 (23.5 %) more tomato products (p = 0.01). 271 (40.0 %) men consumed more protein (p < 0.0001) and 193 (28.6 %) more fruit/vegetable juice (p < 0.0001). Fewer macronutrients were obtained from dairy products (p < 0.01). Men undergoing active monitoring increased their fruit/vegetable juice intake after diagnosis (p = 0.0023) more than men who had surgery or radiotherapy. CONCLUSIONS: Around one-third of men spontaneously adopted a healthier diet and also consumed more 'prostate-healthy' foods following a diagnosis of PC. Dietary choices also differed by radical or monitoring treatments, indicating that men undergoing active surveillance may be more likely to pursue dietary changes as an adjunct therapy. PC survivors can adopt healthier diets, thus providing clinicians with opportunities to support PC survivorship by providing targeted advice beneficial to general and potentially prostate-specific health.
Cancer Causes and Control 03/2013; · 2.88 Impact Factor
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Carolina Bonilla,
Rebecca Gilbert,
John P Kemp,
Nic Timpson,
David M Evans, Jenny L Donovan,
Freddie C Hamdy,
David E Neal,
William D Fraser,
George Davey Smith,
S J Lewis,
Mark Lathrop,
Richard M Martin
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ABSTRACT: BACKGROUND: Ecological and epidemiological studies have identified an inverse association of intensity and duration of sunlight exposure with prostate cancer, which may be explained by a reduction in vitamin D synthesis. Pigmentation traits influence sun exposure and therefore may affect prostate cancer risk. Because observational studies are vulnerable to confounding and measurement error, we used Mendelian randomization to examine the relationship of sun exposure with both prostate cancer risk and the intermediate phenotype, plasma levels of vitamin D. METHODS: We created a tanning, a skin color and a freckling score as combinations of SNPs that have been previously associated with these phenotypes. A higher score indicates propensity to burn, have a lighter skin color and freckles. The scores were tested for association with vitamin D levels (25-hydroxyvitamin-D and 1,25-dihydroxyvitamin-D) and PSA-detected prostate cancer in 3123 white British individuals enrolled in the Prostate Testing for cancer and Treatment (ProtecT) study. RESULTS: The freckling score was inversely associated with 25(OH)D levels (change in 25(OH)D per score unit -0.27; 95%CI: -0.52, -0.01), and the tanning score was positively associated with prostate cancer risk (OR 1.05; 95%CI: 1.02,1.09), after adjustment for population stratification and potential confounders. CONCLUSIONS: Individuals who tend to burn are more likely to spend less time in the sun and consequently have lower plasma vitamin D levels and higher susceptibility to prostate cancer. Impact: The use of pigmentation related genetic scores is valuable for the assessment of the potential benefits of sun exposure with respect to prostate cancer risk.
Cancer Epidemiology Biomarkers & Prevention 02/2013; · 4.12 Impact Factor
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ABSTRACT: PURPOSE: Obesity has been associated with an increased risk of advanced and fatal prostate cancer; adipokines may mediate this association. We examined associations of the adipokines leptin and adiponectin with the stage and grade of PSA-detected prostate cancer. METHODS: We conducted a nested case-control study comparing 311 men with mainly locally advanced (≥T3, N1, or M1 cases) vs. 413 men with localized (T ≤2 & NX-0 & M0 controls) PSA-detected prostate cancer, recruited 2001-2009 from 9 UK regions to the ProtecT study. Associations of body mass index and adipokine levels with prostate cancer stage were determined by conditional logistic regression and with grade (Gleason score ≥7 vs. ≤6) by unconditional logistic regression. RESULTS: Adiponectin was inversely associated with prostate cancer stage in overweight and obese men (OR 0.62; 95 % CI 0.42-0.90; p = 0.01), but not in normal weight men (OR 1.48; 0.77-2.82; p = 0.24) (p for interaction 0.007), or all men (OR 0.86; 0.66-1.11; p = 0.24). There was no compelling evidence of associations between leptin or leptin to adiponectin ratio and prostate cancer stage. No strong associations of adiponectin, leptin, or leptin:adiponectin ratio with grade were seen. CONCLUSIONS: This study provides some evidence that adiponectin levels may be associated with prostate cancer stage, dependent on the degree of adiposity of the man. Our results are consistent with adiponectin countering the adverse effects of obesity on prostate cancer progression.
Cancer Causes and Control 12/2012; · 2.88 Impact Factor
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Santiago Rodriguez,
Osama A Al-Ghamdi,
Kimberley Burrows,
Philip A I Guthrie,
J Athene Lane,
Michael Davis,
Gemma Marsden,
Khalid K Alharbi,
Angela Cox,
Freddie C Hamdy,
David E Neal, Jenny L Donovan,
Ian N M Day
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ABSTRACT: BACKGROUND:Prostate-specific antigen (PSA), a widely used biomarker for prostate cancer (PCa), is encoded by a kallikrein gene (KLK3, kallikrein-related peptidase 3). Serum PSA concentrations vary in the population, with PCa patients generally showing higher PSA concentrations than control individuals, although a small proportion of individuals in the population display very low PSA concentrations. We hypothesized that very low PSA concentrations might reflect gene-inactivating mutations in KLK3 that lead to abnormally reduced gene expression.METHODS:We have sequenced all KLK3 exons and the promoter and searched for gross deletions or duplications in KLK3 in the 30 individuals with the lowest observed PSA concentrations in a sample of approximately 85 000 men from the Prostate Testing for Cancer and Treatment (ProtecT) study. The ProtecT study examines a community-based population of men from across the UK with little prior PSA testing.RESULTS:We observed no stop codons or frameshift mutations, but we did find 30 single-base genetic variants, including 3 variants not described previously. These variants included missense variants that could be functionally inactivating and splicing variants. At this stage, however, we cannot confidently conclude whether these variants markedly lower PSA concentration or activity. More importantly, we identified 3 individuals with different large heterozygous deletions that encompass all KLK3 exons. The absence of a functional copy of KLK3 in these individuals is consistent with their reduced serum PSA concentrations.CONCLUSIONS:The clinical interpretation of the PSA test for individuals with KLK3 gene inactivation could lead to false-negative PSA findings used for screening, diagnosis, or monitoring of PCa.
Clinical Chemistry 11/2012; · 7.91 Impact Factor
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Julius Gudmundsson,
Patrick Sulem,
Daniel F Gudbjartsson,
Gisli Masson,
Bjarni A Agnarsson,
Kristrun R Benediktsdottir,
Asgeir Sigurdsson,
Olafur Th Magnusson,
Sigurjon A Gudjonsson,
Droplaug N Magnusdottir, [......],
Jose I Mayordomo,
Gudmundur V Einarsson,
Rosa B Barkardottir,
Eirikur Jonsson,
Dana Mates,
David E Neal,
Lambertus A Kiemeney,
Unnur Thorsteinsdottir,
Thorunn Rafnar,
Kari Stefansson
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ABSTRACT: In Western countries, prostate cancer is the most prevalent cancer of men and one of the leading causes of cancer-related death in men. Several genome-wide association studies have yielded numerous common variants conferring risk of prostate cancer. Here, we analyzed 32.5 million variants discovered by whole-genome sequencing 1,795 Icelanders. We identified a new low-frequency variant at 8q24 associated with prostate cancer in European populations, rs188140481[A] (odds ratio (OR) = 2.90; P(combined) = 6.2 × 10(-34)), with an average risk allele frequency in controls of 0.54%. This variant is only very weakly correlated (r(2) ≤ 0.06) with previously reported risk variants at 8q24, and its association remains significant after adjustment for all known risk-associated variants. Carriers of rs188140481[A] were diagnosed with prostate cancer 1.26 years younger than non-carriers (P = 0.0059). We also report results for a previously described HOXB13 variant (rs138213197[T]), confirming it as a prostate cancer risk variant in populations from across Europe.
Nature Genetics 10/2012; · 35.53 Impact Factor
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Ali Amin Al Olama,
Zsofia Kote-Jarai,
Fredrick R Schumacher,
Fredrik Wiklund,
Sonja I Berndt,
Sara Benlloch,
Graham G Giles,
Gianluca Severi,
David E Neal,
Freddie C Hamdy, [......],
Shintaro Narita,
Guang-Wen Cao,
Chavdar Slavov,
Vanio Mitev,
Stephen Chanock,
Henrik Gronberg,
Christopher A Haiman,
Peter Kraft,
Douglas F Easton,
Rosalind A Eeles
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ABSTRACT: Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four genome-wide association studies (GWAS) including 5,953 cases of aggressive PrCa and 11,463 controls (men without PrCa). We computed association tests for ~2.6M SNPs and followed up the most significant SNPs by genotyping 49,121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa (OR=1.12 (95% CI 1.03-1.21), P=1.4x10(-8)). This report describes a genetic variant which is associated with aggressive prostate cancer, which is a type of prostate cancer associated with a poorer prognosis.
Human Molecular Genetics 10/2012; · 7.64 Impact Factor
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ABSTRACT: Alcohol is an established carcinogen but not an established risk factor for prostate cancer, despite some recent prospective studies suggesting increased risk among heavy drinkers. The aim of this study was to investigate the role of alcohol on prostate-specific antigen (PSA) levels and prostate cancer risk. 2,400 prostate-specific antigen (PSA) detected prostate cancer cases and 12,700 controls matched on age and general practice were identified through a case-control study nested in the PSA-testing phase of a large UK-based randomized controlled trial for prostate cancer treatment (ProtecT). Linear and multinomial logistic regression models were used to estimate ratios of geometric means (RGMs) of PSA and relative risk ratios (RRRs) of prostate cancer by stage and grade, with 95% confidence intervals (CIs), associated with weekly alcohol intake and drinking patterns. We found evidence of lower PSA (RGM 0.98, 95%CI: 0.98-0.99) and decreased risk of low Gleason-grade (RRR 0.96; 95%CI 0.93-0.99) but increased risk of high-grade prostate cancer (RRR 1.04; 95%CI 0.99-1.08; p(difference) =0.004) per 10 units/week increase in alcohol consumption, not explained by current BMI, blood pressure, co-morbidities, or reverse causation. This is the first large population-based study to find evidence of lower PSA levels for increasing alcohol consumption, with potential public health implications for the detection of prostate cancer. Our results also support a modestly higher risk of high-grade disease for heavy drinkers, but require independent replication to establish the nature of the association of alcohol with low-grade disease, preferably in cohorts with a heterogeneous case-mix. © 2012 Wiley-Liss, Inc.
International Journal of Cancer 10/2012; · 5.44 Impact Factor
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Gisela Orozco,
Chee L Goh,
Ali Amin Al Olama,
Sara Benlloch-Garcia,
Koveela Govindasami,
Michelle Guy,
Kenneth R Muir,
Graham G Giles,
Gianluca Severi,
David E Neal,
Freddie C Hamdy, Jenny L Donovan,
Zsofia Kote-Jarai,
Douglas F Easton,
Steve Eyre,
Rosalind A Eeles
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ABSTRACT: What's known on the subject? and What does the study add? The link between inflammation and cancer has long been reported and inflammation is thought to play a role in the pathogenesis of many cancers, including prostate cancer (PrCa). Over the last 5 years, genome-wide association studies (GWAS) have reported numerous susceptibility loci that predispose individuals to many different traits. The present study aims to ascertain if there are common genetic risk profiles that might predispose individuals to both PrCa and the autoimmune inflammatory condition, rheumatoid arthritis. These results could have potential public heath impact in terms of screening and chemoprevention. OBJECTIVES: • To investigate if potential common pathways exist for the pathogenesis of autoimmune disease and prostate cancer (PrCa). • To ascertain if the single nucleotide polymorphisms (SNPs) reported by genome-wide association studies (GWAS) as being associated with susceptibility to PrCa are also associated with susceptibility to the autoimmune disease rheumatoid arthritis (RA). MATERIALS AND METHODS: • The original Wellcome Trust Case Control Consortium (WTCCC) UK RA GWAS study was expanded to include a total of 3221 cases and 5272 controls. • In all, 37 germline autosomal SNPs at genome-wide significance associated with PrCa risk were identified from a UK/Australian PrCa GWAS. • Allele frequencies were compared for these 37 SNPs between RA cases and controls using a chi-squared trend test and corrected for multiple testing (Bonferroni). RESULTS: • In all, 33 SNPs were able to be analysed in the RA dataset. Proxies could not be located for the SNPs in 3q26, 5p15 and for two SNPs in 17q12. • After applying a Bonferroni correction for the number of SNPs tested, the SNP mapping to CCHCR1 (rs130067) retained statistically significant evidence for association (P= 6 × 10(-4) ; odds ratio [OR]= 1.15, 95% CI: 1.06-1.24); this has also been associated with psoriasis. • However, further analyses showed that the association of this allele was due to confounding by RA-associated HLA-DRB1 alleles. CONCLUSIONS: • There is currently no evidence that SNPs associated with PrCa at genome-wide significance are associated with the development of RA. • Studies like this are important in determining if common genetic risk profiles might predispose individuals to many diseases, which could have implications for public health in terms of screening and chemoprevention.
BJU International 09/2012; · 2.84 Impact Factor
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Iona Cheng,
Gary K Chen,
Hidewaki Nakagawa,
Jing He,
Peggy Wan,
Cathy C Laurie,
Jess Shen,
Xin Sheng,
Loreall C Pooler,
Andrew T Crenshaw, [......],
Lynne R Wilkens,
Kristine R Monroe,
Daniel O Stram,
Kenneth Muir,
Rosalind A Eeles,
Douglas F Easton,
Laurence N Kolonel,
Brian E Henderson,
Loïc Le Marchand,
Christopher A Haiman
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ABSTRACT: BACKGROUND: There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos.METHODS: Our first-stage GWAS of prostate cancer included Japanese (cases/controls = 1,033/1,042) and Latino (cases/controls = 1,043/1,057) from the Multiethnic Cohort (MEC). Significant associations from stage I (P < 1.0 × 10(-4)) were examined in silico in GWAS of prostate cancer (stage II) in Japanese (cases/controls = 1,583/3,386) and Europeans (cases/controls = 1,854/1,894).RESULTS: No novel stage I single-nucleotide polymorphism (SNP) outside of known risk regions reached genome-wide significance. For Japanese, in stage I, the most notable putative novel association was seen with 10 SNPs (P ≤ 8.0 × 10(-6)) at chromosome 2q33; however, this was not replicated in stage II. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage I: OR = 1.45; P = 7.01 × 10(-5) and stage II: OR = 1.58; P = 3.05 × 10(-7)). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele = 1.10; P = 2.71 × 10(-25) and OR = 1.07; P = 1.02 × 10(-16) for Japanese and Latinos, respectively).Conclusion and Impact: Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings show that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos. Cancer Epidemiol Biomarkers Prev; 1-11. ©2012 AACR.
Cancer Epidemiology Biomarkers & Prevention 08/2012; · 4.12 Impact Factor
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ABSTRACT: Assessment of prostate-specific antigen increase with time (PSA growth) is a fundamental component of active surveillance among men with localized prostate cancer. Factors that influence PSA growth, however, are unclear. We evaluated associations of anthropometric and lifestyle factors with age-related PSA growth.
Repeat PSA measures from 404 men, aged 50 to 69 years, with localized prostate cancer undergoing active monitoring were obtained. From log(PSA) measures, age-specific multilevel mixed effect linear models were developed to predict PSA at age 50 years and yearly increase in postdiagnosis PSA. Baseline anthropometric measures, alcohol consumption, occupational class, smoking status, and physical activity were added to the model as covariates.
The median number of repeat PSAs was 13 (range, 2-40), and the mean duration of follow-up was 4.8 years (SD, 2.3). The basic model of age-related PSA growth in men with localized prostate cancer estimated a mean PSA at age 50 of 3.95 ng/mL [95% confidence interval (CI): 3.55 to 4.39] and a yearly increase of 8.50% (95% CI: 7.90% to 9.10%). PSA at age 50 years was 2.1% lower per unit increase in weighted exercise score (95% CI: -3.3 to -0.8), 5.3% lower per 5 cm increase in height (95% CI: -9.4 to -1.1), and 24.5% higher (95% CI: 4.0 to 49.1) in current smokers than never smokers. Similar associations with PSA growth were seen.
Smoking and exercise are modifiable lifestyle factors that may be associated with PSA levels in men with localized prostate cancer undergoing active monitoring/surveillance. Impact: These factors may be useful in understanding etiology of progression. Cancer Epidemiol Biomarkers Prev; 21(10); 1877-85. ©2012 AACR.
Cancer Epidemiology Biomarkers & Prevention 08/2012; 21(10):1877-85. · 4.12 Impact Factor
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ABSTRACT: Context With the routinization of evidence-based medicine and of the randomized-controlled trial (RCT), more patients are becoming 'sites of evidence production' yet, little is known about how they are recruited as participants; there is some evidence that 'substantively valid consent' is difficult to achieve. Objective To explore the views and experiences of nurses recruiting patients to randomized-controlled trials and to examine the extent to which their recruitment practices were patient-centred and patient empowering. Design Semi-structured in-depth interviews; audio recording of recruitment appointments; thematic interactional analysis (drawing on discourse and conversation analysis). Setting and participants Nurses recruiting patients to five publicly funded RCTs and patients consenting to the recording of their recruitment sessions. Main outcome measures The views of recruiting nurses about their recruitment role; the extent to which nurse-patient interactions were patient-centred; the nature of the nurses' interactional strategies and the nature and extent of patient participation in the discussion. Results The nurses had a keen sense of themselves as clinicians and patient advocates and their perceptions of the trial and its interventions were inextricably linked to those of the patients. However, many of their recruitment practices made it difficult for patients to play an active and informed part in the discussion about trial participation, raising questions over the quality of consent decisions. Conclusion Nurses working in patient recruitment to RCTs need to reconcile two different worlds with different demands and ethics. Evidence production, a central task in evidence-based medicine, poses a challenge to patient-centred practice and more research and relevant training are needed.
Health expectations: an international journal of public participation in health care and health policy 06/2012; · 1.80 Impact Factor
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ABSTRACT: PURPOSE: Theory-based approaches are now recommended to design and enact dietary interventions, but their use in cancer trials is unknown. This systematic review examined application of behavior theory to dietary interventions aimed at preventing cancer to improve the design and interpretation of trials. METHODS: Electronic databases were searched (inception-July 2011). Data were synthesized and a theory coding scheme (TCS) used to describe and assess how behavior theory informed interventions. Studies not reporting a dietary behavior intervention informed by a specified behavior change model(s) were excluded. RESULTS: Of 237 potentially eligible studies, only 40 (16.9 %) were relevant, mostly RCTs (34, 85.0 %). Twenty-one interventions targeted diet alone (52.5 %) or integrated diet into a lifestyle intervention (19, 47.5 %). Most (24, 60.0 %) invoked several behavior change models, but only 10 (25.0 %) interventions were reported as explicitly theory-informed and none comprehensively targeted or measured theoretical constructs or tested theoretical assumptions. The 10 theory-informed interventions were more effective at improving diet. CONCLUSIONS: Dietary interventions for cancer prevention improved diet more effectively if they were informed by behavior theory. While behavior theory was often applied to these dietary interventions, they were rarely implemented or described thoroughly. Accurate intervention reporting is essential to assess theoretical quality and facilitate implementation effective behavior change techniques. Guidelines regarding the application and reporting of behavior theory for complex interventions, for example, proposed by the National Institutes of Health and Medical Research Council, should be revised accordingly. Failure to adequately ground dietary interventions in behavior theory may hinder establishing their effectiveness and relationships between diet and cancer.
Cancer Causes and Control 05/2012; · 2.88 Impact Factor
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ABSTRACT: Little is known about factors influencing men's decisions to undergo screening and diagnostic tests for prostate cancer (PCa).
Identify predictors of attendance for prostate-specific antigen (PSA) testing and prostate biopsy.
Literature searches and interviews with men undergoing PSA testing and prostate biopsy formed the basis of a self-report questionnaire designed to identify predictors of health behaviour, which was completed by men eligible for PSA invitation and prostate biopsy. Multitrait scaling analyses established the final questionnaire content. This revised instrument was distributed to a new cohort of men before PSA testing and biopsy invitations were received. Ethical committee approval was obtained from Trent Multicentre Research Ethics Committee (MREC/01/4/025-21/06/2001).
Predictors of health behaviour and attendance rates for PSA test or prostate biopsy were measured. Associations between questionnaire scores and health behaviour (PSA and prostate biopsy attendance) were examined using logistic regression.
The provisional 49-item health behaviour questionnaire was completed by 468 of 810 men (57.8%). Multitrait scaling refined the questionnaire to 26 items in six scales (A: health benefits, B: threats to health, C: barriers to testing, D: health intentions, E: external influences, F: current general health). A total of 1455 of 2657 men (54.8%) completed the revised instrument before invitations for PSA test or biopsy were received; 395 (43.4%) and 434 (91.6%) attended. Strong associations between men's health intentions (scale D) and PSA and biopsy attendance (odds ratio: 1.56 or 3.67, respectively; p<0.001) were observed with modest associations between the other five scales and attendance for PSA testing. Average questionnaire response rates represent the major limitation of this study.
Knowledge and beliefs about PCa and testing predict men's intentions and attendance for PSA testing and prostate biopsy. Understanding men's health behaviour is important for the management of patients seeking PSA testing in general practice.
European urology 01/2012; 62(4):649-55. · 7.67 Impact Factor
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Derek J Rosario,
J Athene Lane,
Chris Metcalfe, Jenny L Donovan,
Andy Doble,
Louise Goodwin,
Michael Davis,
James W F Catto,
Kerry Avery,
David E Neal,
Freddie C Hamdy
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ABSTRACT: To measure the effect of the adverse events within 35 days of transrectal ultrasound guided biopsy from the perspective of asymptomatic men having prostate specific antigen (PSA) testing; to assess early attitude to re-biopsy; to estimate healthcare resource use associated with adverse events due to biopsy; and to develop a classification scheme for reporting adverse events after prostate biopsy.
Prospective cohort study (Prostate Biopsy Effects: ProBE) nested within Prostate Testing for Cancer and Treatment (ProtecT) study. Participants Between 1999 and 2008, 227,000 community dwelling men aged 50-69 years were identified at 352 practices and invited to counselling about PSA testing. 111,148 attended a nurse led clinic in the community, and 10,297 with PSA concentrations of 3-20 ng/mL were offered biopsy within ProtecT. Between February 2006 and May 2008, 1147/1753 (65%) eligible men (mean age 62.1 years, mean PSA 5.4 ng/mL) having 10 core transrectal ultrasound guided biopsy under antibiotic cover in the context of ProtecT were recruited to the ProBE study.
Purpose designed questionnaire administered at biopsy and 7 and 35 days after the procedure to measure frequency and effect of symptoms related to pain, infection, and bleeding; patients' attitude to repeat biopsy assessed immediately after biopsy and 7 days later; participants' healthcare resource use within 35 days of biopsy evaluated by questionnaire, telephone follow-up, and medical note review; each man's adverse event profile graded according to symptoms and healthcare use.
Pain was reported by 429/984 (43.6%), fever by 172/985 (17.5%), haematuria by 642/976 (65.8%), haematochezia by 356/967 (36.8%), and haemoejaculate by 605/653 (92.6%) men during the 35 days after biopsy. Fewer men rated these symptoms as a major/moderate problem-71/977 (7.3%) for pain, 54/981 (5.5%) for fever, 59/958 (6.2%) for haematuria, 24/951 (2.5%) for haematochezia, and 172/646 (26.6%) for haemoejaculate. Immediately after biopsy, 124/1142 (10.9%, 95% confidence interval 9.2 to 12.8) men reported that they would consider further biopsy a major or moderate problem: seven days after biopsy, this proportion had increased to 213/1085 (19.6%, 17.4% to 22.1%). A negative attitude to repeat biopsy was associated with unfavourable experience after the first biopsy, particularly pain at biopsy (odds ratio 8.2, P<0.001) and symptoms related to infection (7.9, P<0.001) and bleeding (4.2, P<0.001); differences were evident between centres (P<0.001). 119/1147 (10.4%, 8.7% to 12.3%) men reported consultation with a healthcare professional (usually their general practitioner), most commonly for infective symptoms. Complete data for all index symptoms at all time points were available in 851 participants. Symptoms and healthcare use could be used to grade these men as follows: grade 0 (no symptoms/contact) 18 (2.1%, 1.3% to 3.3%); grade 1 (minor problem/no contact) 550 (64.6%, 61.4% to 67.8%); grade 2 (moderate/major problem or contact) 271 (31.8%, 28.8% to 35.1%); grade 3 (hospital admission) 12 (1.4%, 0.8% to 2.4%); and grade 4 (death) 0. Grade of adverse event was associated with an unfavourable attitude to repeat biopsy (Kendall's τ-b ordinal by ordinal 0.29, P<0.001).
This study with a high response rate of 89% at 35 days in men undergoing biopsy in the context of a randomised controlled trial has shown that although prostate biopsy is well tolerated by most men, it is associated with significant symptoms in a minority and affects attitudes to repeat biopsy and primary care resource use. These findings will inform men who seek PSA testing for detection of prostate cancer and assist their physicians during counselling about the potential risks and effect of biopsy. Variability in the adverse event profile between centres suggests that patients' outcomes could be improved and healthcare use reduced with more effective administration of local anaesthetic and antibiotics. Trial registration Current Controlled Trials ISRCTN20141297.
BMJ (Clinical research ed.). 01/2012; 344:d7894.
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Trials 12/2011; 12 Suppl 1:A124. · 2.02 Impact Factor
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ABSTRACT: Circulating insulin-like growth factor-I (IGF-I) has been studied extensively in prostate cancer, but there is still little information about IGFs and IGF-binding proteins (IGFBP) in cancers detected by the prostate-specific antigen (PSA) test. Here, we report the findings of a U.K.-based case-control study to investigate circulating IGFs and IGFBPs in PSA-detected prostate cancer with regard to their potential associations with different cancer stages or grades. PSA testing was offered to 110,000 men aged 50 to 69 years from 2002 to 2009. Participants with an elevated level of PSA (≥3.0 ng/mL) underwent prostate biopsy and measurements of blood serum IGF-I, IGF-II, IGFBP-2, and IGFBP-3 obtained at recruitment. We found that serum levels of IGF-II (OR per SD increase: 1.16; 95% CI: 1.08-1.24; P(trend) < 0.001), IGFBP-2 (1.18; 1.06-1.31; P(trend) < 0.01) and IGFBP-3 (1.27; 1.19-1.36; P(trend) < 0.001), but not IGF-I (0.99; 0.93-1.04; P(trend) = 0.62), were associated with PSA-detected prostate cancer. After controlling for IGFBP-3, IGF-II was no longer associated (0.99; 0.91-1.08; P(trend) = 0.62) and IGF-I was inversely associated (0.85; 0.79-0.91; P(trend) < 0.001) with prostate cancer. In addition, no strong associations existed with cancer stage or grade. Overall, these findings suggest potentially important roles for circulating IGF-II, IGFBP-2, and IGFBP-3 in PSA-detected prostate cancer, in support of recent in vitro evidence. Although our findings for IGF-I agree with previous results from PSA screening trials, they contrast with positive associations in routinely detected disease, suggesting that reducing levels of circulating IGF-I might not prevent the initiation of prostate cancer but might, nonetheless, prevent its progression.
Cancer Research 11/2011; 72(2):503-15. · 7.86 Impact Factor
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ABSTRACT: A psychometrically robust patient-completed questionnaire for anal incontinence, which reflects issues of importance to both clinicians and patients, was lacking for assessment purposes.
This study aimed to determine the psychometric properties of a new questionnaire developed to address this need, the International Consultation on Incontinence Questionnaire-Bowels module.
Qualitative studies were used to refine the developmental version of the questionnaire. Quantitative studies were conducted to evaluate its psychometric properties.
Patients were invited to complete the questionnaire via postal administration.
Two hundred sixty-one patients with known bowel symptoms participated in the study (244 females, 17 males; mean age, 59.7 years (range, 24-92)).
The aspects of validity were evaluated in comparison with available evidence, responses to existing instruments, and physiological findings. Reliability was assessed through repeat administration of the questionnaire and evaluation of internal consistency by the Cronbach α coefficient. Responsiveness following treatment was evaluated by the use of the Wilcoxon signed rank test. Exploratory factor analysis was used to derive the final version of the questionnaire with evidence from the above studies.
The final questionnaire contains 17 questions arranged in 3 scored domains: bowel pattern, bowel control, and quality of life, with 4 unscored items included to evaluate important issues from a clinical or patient perspective. The questionnaire demonstrated acceptable validity, "good" to "very good" reliability, and reasonable response to changes in symptom and quality-of-life status following intervention.
Response rates varied according to location.
The International Consultation on Incontinence Questionnaire Bowel module is a psychometrically robust, self-report instrument for the evaluation of anal incontinence and its impact on quality of life. It is suitable for use in individuals with anal incontinence of varying causes. It includes a scoring system for use in clinical practice and research.
Diseases of the Colon & Rectum 10/2011; 54(10):1235-50. · 3.13 Impact Factor
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Simon N Stacey,
Patrick Sulem,
Aslaug Jonasdottir,
Gisli Masson,
Julius Gudmundsson,
Daniel F Gudbjartsson,
Olafur T Magnusson,
Sigurjon A Gudjonsson,
Bardur Sigurgeirsson,
Kristin Thorisdottir, [......],
Eduardo Nagore,
Ulla Vogel,
Lambertus A Kiemeney,
Rajiv Kumar,
José I Mayordomo,
Jon H Olafsson,
Augustine Kong,
Unnur Thorsteinsdottir,
Thorunn Rafnar,
Kari Stefansson
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ABSTRACT: To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
Nature Genetics 09/2011; 43(11):1098-103. · 35.53 Impact Factor
