Population-based proband-oriented pedigree information system: application to hypertension with population-based screening data (KCIS No. 25)

Objective To develop a population-based probandoriented pedigree information system that can be easily applied to various diseases in genetic epidemiological studies, making allowance for the capture of theoretical family relationships. Designs and Measurements A population-based proband-oriented pedigree information system with ties of consanguinity based on both population-based household registry data and Keelung Community Integrated Screening data was proposed to build a comprehensive extended family pedigree structure to accommodate a series of genetic studies on different diseases. We also developed an algorithm to efficiently assess how well theoretical family relationships affecting the occurrence of diseases across three generations with respect to the relative relationship score, a quantitative indicator of genetic influence, were captured. Results We applied this population-based probandoriented pedigree information system to estimate the rate of hypertension with various relative relationships given the selection of probands. The degree of capturing complete familial relationships was assessed for three generations. The risk for early onset of hypertension was proportional to the proband-oriented relative relationship score with 2% increased risk and 1% correction for incomplete capture. Conclusions The population-based proband-oriented pedigree information system is powerful and can support various genetic descriptive and analytic epidemiological studies

Assessing interactions of two loci (rs4242382 and rs10486567) in familial prostate cancer : statistical evaluation of epistasis

Understanding the impact of multiple genetic variants and their interactions on the disease penetrance of familial multiple prostate cancer is very relevant to the overall understanding of carcinogenesis. We assessed the joint effect of two loci on rs4242382 at 8q24 and rs10486567 at 7p15.2 to this end. We analyzed the data from a Finnish family-based genetic study, which was composed of 947 men including 228 cases in 75 families, to evaluate the respective effects of the two loci on the disease penetrance; in particular, the occurrence and number of prostate cancer cases within a family were utilized to evaluate the interactions between the two loci under the additive and multiplicative Poisson regression models. The risk alleles A at rs4242382 (OR = 1.14, 95% CI 1.08–1.19, P<0.0001) and a risk allele A at rs10486567 (OR = 1.06, 96%CI 1.01–1.11, P = 0.0208) were found to be associated with an increased risk of familial PrCa, especially with four or more cases within a family. A multiplicative model fitted the joint effect better than an additive model (likelihood ratio test X2 = 13.89, P<0.0001). The influence of the risk allele A at rs10486567 was higher in the presence of the risk allele A at rs4242382 (OR = 1.09 (1.01–1.18) vs. 1.01 (0.95–1.07)). Similar findings were observed in non-aggressive PrCa, but not in aggressive PrCa. We demonstrated that two loci (rs4242382 and rs10486567) are highly associated with familial multiple PrCa, and the gene-gene interaction or statistical epistasis was consistent with the Fisher's multiplicative model. These loci's association and epistasis were observed for non-aggressive but not for aggressive tumors. The proposed statistical model can be further developed to accommodate multi-loci interactions to provide further insights into epistasis.Public Library of Science open acces

Risk Prediction of Prostate Cancer with Single Nucleotide Polymorphisms and Prostate Specific Antigen

Purpose:Combined information on single nucleotide polymorphisms and prostate specific antigen offers opportunities to improve the performance of screening by risk stratification. We aimed to predict the risk of prostate cancer based on prostate specific antigen together with single nucleotide polymorphism information.Materials and Methods:We performed a prospective study of 20,575 men with prostate specific antigen testing and 4,967 with a polygenic risk score for prostate cancer based on 66 single nucleotide polymorphisms from the Finnish population based screening trial of prostate cancer and 5,269 samples of 7 single nucleotide polymorphisms from the Finnish prostate cancer DNA study. A Bayesian predictive model was built to estimate the risk of prostate cancer by sequentially combining genetic information with prostate specific antigen compared with prostate specific antigen alone in study subjects limited to those with prostate specific antigen 4 ng/ml or above.Results:The posterior odds of prostate cancer based on 7 single nucleotide polymorphisms together with the prostate specific antigen level ranged from 3.7 at 4 ng/ml, 14.2 at 6 and 40.7 at 8 to 98.2 at 10 ng/ml. The ROC AUC was elevated to 88.8% (95% CI 88.6-89.1) for prostate specific antigen combined with the risk score based on 7 single nucleotide polymorphisms compared with 70.1% (95% CI 69.6-70.7) for prostate specific antigen alone. It was further escalated to 96.7% (95% CI 96.5-96.9) when all prostate cancer susceptibility polygenes were combined.Conclusions:Expedient use of multiple genetic variants together with information on prostate specific antigen levels better predicts the risk of prostate cancer than prostate specific antigen alone and allows for higher prostate specific antigen cutoffs. Combined information also provides a basis for risk stratification which can be used to optimize the performance of prostate cancer screening.Peer reviewe

Beneficial Effect of Consecutive Screening Mammography Examinations on Mortality from Breast Cancer: A Prospective Study

BackgroundPreviously, the risk of death from breast cancer was analyzed for women participating versus those not participating in the last screening examination before breast cancer diagnosis. Consecutive attendance patterns may further refine estimates.PurposeTo estimate the effect of participation in successive mammographic screening examinations on breast cancer mortality.Materials and MethodsParticipation data for Swedish women eligible for screening mammography in nine counties from 1992 to 2016 were linked with data from registries and regional cancer centers for breast cancer diagnosis, cause, and date of death (Uppsala University ethics committee registration number: 2017/147). Incidence-based breast cancer mortality was calculated by whether the women had participated in the most recent screening examination prior to diagnosis only (intermittent participants), the penultimate screening examination only (lapsed participants), both examinations (serial participants), or neither examination (serial nonparticipants). Rates were analyzed with Poisson regression. We also analyzed incidence of breast cancers proving fatal within 10 years.ResultsData were available for a total average population of 549 091 women (average age, 58.9 years ± 6.7 [standard deviation]). The numbers of participants in the four groups were as follows: serial participants, 392 135; intermittent participants, 41 746; lapsed participants, 30 945; and serial nonparticipants, 84 265. Serial participants had a 49% lower risk of breast cancer mortality (relative risk [RR], 0.51; 95% CI: 0.48, 0.55; P P ConclusionWomen participating in the last two breast cancer screening examinations prior to breast cancer diagnosis had the largest reduction in breast cancer death. Missing either one of the last two examinations conferred a significantly higher risk.Published under a CC BY 4.0 license.</p

Developing a Prediction Model for 7-Year and 10-Year All-Cause Mortality Risk in Type 2 Diabetes Using a Hospital-Based Prospective Cohort Study

Leveraging easily accessible data from hospitals to identify high-risk mortality rates for clinical diabetes care adjustment is a convenient method for the future of precision healthcare. We aimed to develop risk prediction models for all-cause mortality based on 7-year and 10-year follow-ups for type 2 diabetes. A total of Taiwanese subjects aged ≥18 with outpatient data were ascertained during 2007–2013 and followed up to the end of 2016 using a hospital-based prospective cohort. Both traditional model selection with stepwise approach and LASSO method were conducted for parsimonious models’ selection and comparison. Multivariable Cox regression was performed for selected variables, and a time-dependent ROC curve with an integrated AUC and cumulative mortality by risk score levels was employed to evaluate the time-related predictive performance. The prediction model, which was composed of eight influential variables (age, sex, history of cancers, history of hypertension, antihyperlipidemic drug use, HbA1c level, creatinine level, and the LDL /HDL ratio), was the same for the 7-year and 10-year models. Harrell’s C-statistic was 0.7955 and 0.7775, and the integrated AUCs were 0.8136 and 0.8045 for the 7-year and 10-year models, respectively. The predictive performance of the AUCs was consistent with time. Our study developed and validated all-cause mortality prediction models with 7-year and 10-year follow-ups that were composed of the same contributing factors, though the model with 10-year follow-up had slightly greater risk coefficients. Both prediction models were consistent with time

Correlation and presentation of thyroid functional status with thyroid autoantibodies in long-term follow-up of autoimmune thyroiditis: A study of 116 cases

The most common diagnostic finding of autoimmune thyroid disease (AITD) is the presence of antithyroid antibodies. While autoimmune thyroiditis (AT) is a common AITD, aspiration cytology is one of the important diagnostic tools of AT. Methods: We evaluated 116 AT patients with ultrasound-guided aspiration cytology and then analyzed the correlation between thyroid hormone status and thyroid autoantibodies. This was a retrospective analysis with prospective collection of data with a mean follow-up period of 68.8 ± 37.8 months. The patients were classified as either euthyroid, hypothyroid, or hyperthyroid (HT). Of the 116 patients, 22 were hypothyroid, 37 were euthyroid, and 57 were HT. Results: During the follow-up period, 95.5% of the hypothyroid group remained hypothyroid and only one patient improved to euthyroid. In the euthyroid group, 16.2% progressed to hypothyroid and 83.8% remained euthyroid. In the HT group, 8.7% progressed to hypothyroid, 70.2% progressed to euthyroid, and 21.1% remained HT. Most patients with a high titer of thyroglobulin antibody (TgAb) will progress to hypothyroid, and patients with a high titer of thyroid stimulating hormone (TSH) receptor antibody (TRAb) will remain HT. Strong correlations between thyroid functional status and positive number of thyroid autoantibodies were seen in this study. Patients with all the three antibodies positive had a high prevalence of hyperthyroidism. Conclusion: In our study, most patients were HT; this may be because of the early diagnosis and treatment of AT in our clinic. Although antithyroperoxidase antibody (TPOAb) is a hallmark antibody of HT, it cannot predict the initial presentation and clinical outcome

Effectiveness of advice from physician and nurse on smoking cessation stage in Taiwanese male smokers attending a community-based integrated screening program

Introduction A screening program provides a teachable moment for primary prevention such as encouraging smoking cessation. However, little is known about the efficacy of smoking cessation intervention delivered to the general population through a community-based screening program. Material and Methods A quasi-experimental untreated control design with pre-test and post-test was conducted with 42 subjects receiving advice from physician and nurses (the PNA group), 39 receiving an informational leaflet (the leaflet group), and 308 control subjects. Results The overall rate of reaching the action stage was 25 %, 5.7 %, and 7.8 in the PNA group, the leaflet group, and the control group, respectively. In approximately 45–60 % of all participants, the stage remained unchanged. Such an association between the intervention groups and stage changes was statistically significant (p = 0.02). The PNA group was more likely to have the improvement of stage (forward transition toward action stage) than the control group [adjusted odds ratio (aOR) = 2.27 (1.07–4.84)]. Deterioration (backward transition toward precontemplation) in the PNA intervention group was 37 % lower than that in the control group [aOR = 0.63 (0.20–2.01)]. Conclusions This study demonstrated that smoking cessation advice from physician and nurse is conducive to smoking cessation, as shown by greater movement toward and less movement away from smoking cessation through a community-based integrated screening platform