Objective: To evaluate mainstream genetic testing using cancer-based criteria in patients with cancer.
Design, Setting, and Participants: A quality improvement study and cost-effectiveness analysis of different BRCA testing selection criteria and access procedures to evaluate feasibility, acceptability, and mutation detection performance was conducted at the Royal Marsden National Health Service Foundation Trust as part of the Mainstreaming Cancer Genetics (MCG) Programme. Participants included 1184 patients with cancer who were undergoing genetic testing between September 1, 2013, and February 28, 2017.
Main Outcomes and Measures: Mutation rates, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were the primary outcomes.
Results: Of the 1184 patients (1158 women [97.8%]) meeting simple cancer-based criteria, 117 had a BRCA mutation (9.9%). The mutation rate was similar in retrospective United Kingdom (10.2% [235 of 2294]) and prospective Malaysian (9.7% [103 of 1061]) breast cancer studies. If traditional family history criteria had been used, more than 50% of the mutation-positive individuals would have been missed. Of the 117 mutation-positive individuals, 115 people (98.3%) attended their genetics appointment and cascade to relatives is underway in all appropriate families (85 of 85). Combining with the equivalent ovarian cancer study provides 5 simple cancer-based criteria for BRCA testing with a 10% mutation rate: (1) ovarian cancer; (2) breast cancer diagnosed when patients are 45 years or younger; (3) 2 primary breast cancers, both diagnosed when patients are 60 years or younger; (4) triple-negative breast cancer; and (5) male breast cancer. A sixth criterion-breast cancer plus a parent, sibling, or child with any of the other criteria-can be added to address family history. Criteria 1 through 5 are considered the MCG criteria, and criteria 1 through 6 are considered the MCGplus criteria. Testing using MCG or MCGplus criteria is cost-effective with cost-effectiveness ratios of $1330 per discounted QALYs and $1225 per discounted QALYs, respectively, and appears to lead to cancer and mortality reductions (MCG: 804 cancers, 161 deaths; MCGplus: 1020 cancers, 204 deaths per year over 50 years). Use of MCG or MCGplus criteria might allow detection of all BRCA mutations in patients with breast cancer in the United Kingdom through testing one-third of patients. Feedback questionnaires from 259 patients and 23 cancer team members (12 oncologists, 8 surgeons, and 3 nurse specialists) showed acceptability of the process with 100% of patients pleased they had genetic testing and 100% of cancer team members confident to approve patients for genetic testing. Use of MCGplus criteria also appeared to be time and resource efficient, requiring 95% fewer genetic consultations than the traditional process.
Conclusions and Relevance: This study suggests that mainstream testing using simple, cancer-based criteria might be able to efficiently deliver consistent, cost-effective, patient-centered BRCA testing.
MATERIALS AND METHODS: This is a cross-sectional study where women aged between 20-80 years were recruited via convenient sampling from villages in Long Banga, Sarawak over a five-day outreach programme. Cervicovaginal selfsamples were obtained and screened for the presence of high-risk human papillomavirus DNA (HR-HPV) using the careHPVTM Test. A self-administered questionnaire was also administered to determine the sociodemographic and perception towards the self-sampling method.
RESULTS: The 55 women recruited consist of ethnic backgrounds of Penan (58.18%), Kenyah (25.45%), Iban (5.45%), Saban (3.64%), Kelabit (3.64%), Malay (1.82%) and Chinese (1.82%). The prevalence of HR-HPV was 1.85% (n=1/55). Nearly 80% of the women were unemployed, and more than half have had attended primary education. Nine (16.4%) have heard about HPV, and seven (13%) knew HPV infection could cause cervical cancer. Three of them had HPV vaccination, and only one (1.85%) knew the brand of the HPV vaccine. Although 40% preferred self-sampling over clinician-collection, only ten (18.2%) women have completed the self-collection perception questionnaire.
CONCLUSION: Primary HPV DNA screening using the selfsampling method can be carried out in the remote areas during the COVID-19 pandemic without compromising mobility restriction.
STUDY DESIGN: The present study was conducted on 151 women with gynecological cancers as the case group and 152 healthy women with no history of such cancers as control group. The dematographic details of participants from both control and case groups were collected using a checklist, and the pattern of their fingerprints was prepared and examined. The data were analyzed for their significance using chi-square test and t- test. Odds ratio with 95% confidence intervals were calculated.
RESULTS: Dermatoglyphic analysis showed that arch and loop patterns significantly changed in cases group as compared to control. However, the odds ratio suggested that loop pattern in 6 or more fingers might be a risk factor for developing gynecological cancers.
CONCLUSION: Our results showed that there is an association between fingerprint patterns and gynecological cancers and so, dermatoglyphic analysis may aid in the early diagnosis of these cancers.
METHODS: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV.
RESULTS: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml-l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers.
CONCLUSIONS: PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.
METHODS: A cross-sectional survey was conducted among primary care physicians (PCPs) in public primary care clinics in Kuala Lumpur, Malaysia. A 30-item self-administered questionnaire was used to assess the knowledge and practice of CRC screening.
RESULTS: The response rate was 86.4% (n = 197/228). Less than half (39.1%) of the respondents answered correctly for all risk stratification scenarios. Mean knowledge score on CRC screening modalities was 48.7% ± 17.7%. The knowledge score was positively associated with having postgraduate educational qualification and usage of screening guidelines. Overall, 69.9% of PCPs reported that they practised screening. However, of these, only 25.9% of PCPs screened over 50% of all eligible patients. PCPs who agreed that screening was cost-effective (odds ratio [OR] 3.34, 95% confidence interval [CI] 1.69‒6.59) and those who agreed that they had adequate resources in their locality (OR 1.92, 95% CI 1.01‒3.68) were more likely to practise screening. Knowledge score was not associated with the practice of screening (p = 0.185).
CONCLUSION: Knowledge and practice of CRC screening was inadequate among PCPs. Knowledge of screening did not translate into its practice. PCPs' perceptions about cost-effectiveness of screening and adequate resources were important determinants of the practice of screening.
RESULTS: The calibration curve showed a linear range between 0.01 fM to 0.01 nM with a limit of detection 0.05 fM. The results showed that the optimum concentration for DNA probe was 5 µM. The good performance of the proposed biosensor was achieved through hybridization of DNA probe-modified SPCE with extracted DNA from clinical samples.
CONCLUSIONS: According to the investigated results, this biosensor can be introduced as a proprietary, accurate, sensitive, and rapid diagnostic method of HPV 18 in the polymerase chain reaction (PCR) of real samples.
OBJECTIVE: To report the first year's screening results for all men at enrollment in the study.
DESIGN, SETTING AND PARTICIPANTS: We recruited men aged 40-69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrollment, and those men with PSA >3 ng/ml were offered prostate biopsy.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types.
RESULTS AND LIMITATIONS: We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%-double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups.
CONCLUSIONS: The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease.
PATIENT SUMMARY: In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment.
METHODS: 417 patients presenting with haematuria were assessed in our Urology Unit. Following confirmation of haematuria, these patients were subjected to imaging techniques and flexible cystoscopy. Parameters analysed included clinical characteristics, imaging results, flexible cystoscopy findings, time delay to diagnoses and eventual treatment and final diagnoses of all cases.
RESULTS: 390 haematuria cases were analysed from 417 consecutive patients with haematuria. After 27 cases were excluded as they had previous history, 245 microscopic and 145 macroscopic. Age range was 17 to 95 years old with predominance of 152 females to 239 males. The racial distribution included 180 Chinese, 100 Indians,95 Malays and 15 other races. The final diagnoses were benign prostatic hyperplasia (22.6%), no cause found (22.3%), other causes (18.7%), urolithiasis (11.5%), urinary tract infection UTI (10.8%), non specific cystitis (10.3%), bladder tumours (2.8%) and other genitourinary tumours (1%). 11 new cases (2.8%) of bladder cancers were diagnosed, with a mean age of 59 years. Only 3 of 245 (1.2%) patients with microscopic haematuria had newly diagnosed bladder tumour compared with 8 of 145 (5.5%) patients with frank haematuria (p=0.016). Mean time taken from onset of symptoms to diagnosis of bladder cancer was 53.3 days with definitive treatment (TURBT) in 20.1 days from diagnosis.
CONCLUSION: - This study has highlighted the common causes of haematuria in our local setting. We recommend that full and appropriate investigations be carried out on patients with frank haematuria especially those above 50 years old in order to provide earlier detection and prompt management of bladder diseases especially tumours.
METHODS: A cross-sectional survey was conducted at the four outpatient clinics of general hospitals in Tehran during the period from July through October, 2009. Bi-variate analyses and multi-variate binary logistic regression were employed to find the socio- demographic predictors of mammography utilization among participants.
RESULTS: The rate of mammography participation was 21.5% and relatively high because of access to general hospital services. More women who had undergone mammography were graduates from university or college, had full-time or part-time employment, were insured whether public or private, reported a positive family history of breast cancer, and were in the middle income level (P <0.01).The largest number of participating women was in the age range of 41 to 50 years. The results of multivariate logistic regression further showed that education (95%CI: 0.131-0.622), monthly income (95%CI: 0.038-0.945), and family history of breast cancer (95%CI: 1.97-9.28) were significantly associated (all P <0.05)with mammography participation.
CONCLUSIONS: The most important issue for a successful screening program is participation. Using a random sample, this study found that the potential predictor variables of mammography participation included a higher education level, a middle income level, and a positive family history of breast cancer for Iranian women after adjusting for all other demographic variables in the model.