scholarly journals Family history assessment significantly enhances delivery of precision medicine in the genomics era

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Yasmin Bylstra ◽  
Weng Khong Lim ◽  
Sylvia Kam ◽  
Koei Wan Tham ◽  
R. Ryanne Wu ◽  
...  
Keyword(s):  
Family History ◽  
Cancer Risk ◽  
Clinical Care ◽  
Genomic Analysis ◽  
Population Level ◽  
Cancer Genes ◽  
Family History Information ◽  
Screening Programs ◽  
Family History Assessment ◽  
Risk Of Cancer

Abstract Background Family history has traditionally been an essential part of clinical care to assess health risks. However, declining sequencing costs have precipitated a shift towards genomics-first approaches in population screening programs rendering the value of family history unknown. We evaluated the utility of incorporating family history information for genomic sequencing selection. Methods To ascertain the relationship between family histories on such population-level initiatives, we analysed whole genome sequences of 1750 research participants with no known pre-existing conditions, of which half received comprehensive family history assessment of up to four generations, focusing on 95 cancer genes. Results Amongst the 1750 participants, 866 (49.5%) had high-quality standardised family history available. Within this group, 73 (8.4%) participants had an increased family history risk of cancer (increased FH risk cohort) and 1 in 7 participants (n = 10/73) carried a clinically actionable variant inferring a sixfold increase compared with 1 in 47 participants (n = 17/793) assessed at average family history cancer risk (average FH risk cohort) (p = 0.00001) and a sevenfold increase compared to 1 in 52 participants (n = 17/884) where family history was not available (FH not available cohort) (p = 0.00001). The enrichment was further pronounced (up to 18-fold) when assessing only the 25 cancer genes in the American College of Medical Genetics (ACMG) Secondary Findings (SF) genes. Furthermore, 63 (7.3%) participants had an increased family history cancer risk in the absence of an apparent clinically actionable variant. Conclusions These findings demonstrate that the collection and analysis of comprehensive family history and genomic data are complementary and in combination can prioritise individuals for genomic analysis. Thus, family history remains a critical component of health risk assessment, providing important actionable data when implementing genomics screening programs. Trial registration ClinicalTrials.gov NCT02791152. Retrospectively registered on May 31, 2016.

scholarly journals Family History Assessment Significantly Enhances Delivery of Precision Medicine in the Genomics Era

2020 ◽  
Author(s):  
Yasmin Bylstra ◽  
Weng Khong Lim ◽  
Sylvia Kam ◽  
Koei Wan Tham ◽  
R. Ryanne Wu ◽  
...  
Keyword(s):  
Family History ◽  
Cancer Risk ◽  
Clinical Care ◽  
Fold Increase ◽  
Genomic Sequencing ◽  
Cancer Genes ◽  
Screening Programs ◽  
Family History Assessment ◽  
Potential Impact ◽  
Group 2

AbstractBackgroundFamily history has traditionally been an essential part of clinical care to assess health risks. However, declining sequencing costs have precipitated a shift towards genomics-first approaches in population screening programs, with less emphasis on family history assessment. We evaluated the utility of family history for genomic sequencing selection.MethodsWe analysed whole genome sequences of 1750 healthy research participants, with and without preselection based on standardised family history collection, screening 95 cancer genes.ResultsThe frequency of likely pathogenic/ pathogenic (LP/P) variants in 884 participants with no family history available (FH not available group) (2%) versus 866 participants with family history available (FH available group) (3.1%) was not significant (p=0.158). However, within the FH available group, amongst 73 participants with an increased family history cancer risk (increased FH risk), 1 in 7 participants carried a LP/P variant inferring a six-fold increase compared with 1 in 47 participants assessed at average family history cancer risk (average FH risk) and a seven-fold increase compared to the FH not available group. The enrichment was further pronounced (up to 18-fold) when assessing the 25 cancer genes in the ACMG 59-gene panel. Furthermore, 63 participants had an increased family history cancer risk in absence of an apparent LP/P variant.ConclusionOur findings show that systematic family history collection remains critical for health risk assessment, providing important actionable data and augmenting the yield from genomic data. Family history also highlights the potential impact of additional hereditary, environmental and behavioural influences not reflected by genomic sequencing.

Abstract 434: The Majority of Outpatients With Severe Hypercholesterolemia at an Academic Tertiary Centre Have Not Been Screened for FH

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Ezim Ajufo ◽  
Masako Ueda ◽  
Erik Hossain ◽  
Tracey Sikora ◽  
Scott M Damrauer ◽  
...  
Keyword(s):  
Family History ◽  
Clinical Care ◽  
University Of Pennsylvania ◽  
Family History Information ◽  
Tertiary Centre ◽  
The Us ◽  
Statin Prescription ◽  
History Of ◽  
Ascvd Risk ◽  
The University

Background: National and International guidelines recommend, as a minimum, that individuals with LDL-C ≥190mg/dL are asked about a family history of ASCVD and hypercholesterolemia to screen for familial hypercholesterolemia (FH), a monogenic condition that carries considerable ASCVD risk. However, FH is grossly underdiagnosed and undertreated in the US. One reason for this may be failure to screen severely hypercholesterolemic individuals for FH. Hypothesis: We evaluated the hypothesis that poor identification of FH might be due to inadequate screening for FH among individuals with severe hypercholesterolemia. Methods: An EHR query was used to identify active adult patients in the University of Pennsylvania outpatient EHR database (N=310 802) with LDL-C≥220mg/dL, excluding secondary causes of hypercholesterolemia. The EHR was then systematically reviewed for structured notation of family history information. Result: The query identified 3,475 individuals with severely elevated LDL-C. Among them, only 47.9% (1666) had family history data relating to ASCVD (968), hypercholesterolemia (336) or both (362) in the EHR. The history was positive in 94.2% (1569) of these cases. Overall, patients with LDL-C ≥220mg/dL were more likely to be screened (OR 1.57; 95% CI 1.47-1.68) than those with LDL <220mg/dL. Within the former group, the odds of being screened were higher in Caucasians (OR 1.52; 95% CI 1.33-1.75), with more severe LDL-C elevation or a history of ASCVD (OR 1.36; 95% CI 1.10 - 1.67). Conversely, the presence of diabetes (OR 0.73; 95% CI 0.61-0.86) or hypertension (OR 0.82; 95% CI 0.72-0.94), made screening less likely to occur. Interestingly, the setting of clinical care was also important; individuals seen in secondary care (OR 1.68; 95% CI 1.41-2.26), general (OR 1.69, 95% CI 1.47-1.95) or preventative cardiology (OR 1.82; 95% CI 1.47-2.25) were more likely to be screened. Finally, statin prescription was more common in those screened (OR 1.39; 95% CI 1.16-1.88), but this did not affect LDL-C goal achievement. Conclusion: At a large academic centre, the majority of outpatients with severe hypercholesterolemia had no record of being screened for FH. This report sheds light on factors that might be relevant to the underdiagnosis of FH in the US.

Demographic variation and risk factors regarding breast cancer among female in Southern Punjab, Pakistan

2021 ◽  
pp. 1-16
Author(s):  
Waheed Ahmad ◽  
Sabika Firasat ◽  
Muhammad Sohail Akhtar ◽  
Kiran Afshan ◽  
Kaukab Jabeen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Logistic Regression ◽  
Family History ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Conditional Logistic Regression ◽  
Positive Family History ◽  
Study Cohort ◽  
Screening Programs

Objective: Breast cancer is a second major cause of female death worldwide. This study aimed to explore epidemiology, clinical profiles and contribution of reproductive and non-reproductive risk factors in breast cancer development among females from South Punjab, Pakistan. Methods: Data was collected through hospitals between October 2017 and March 2018 and study got approval by Bioethical Committee of Quaid-i-Azam University in September, 2017. A total of 163 cases and 163 age-matched controls were recruited through non-probability consecutive sampling method. All histologically confirmed patients irrespective of age, family history, clinical presentation and histopathological type were included in the study as cases. Patients, who were not willing to participate were excluded from the study. Details regarding socio-demographic characteristics, family history of cancer, reproductive health and lifestyle factors were recorded using a structured questionnaire. Conditional logistic regression was performed to calculate odds ratios at 95% confidence intervals for breast cancer by menstrual and reproductive factors after adjustment of potential confounders. Conditional logistic regression was also applied for various demographic and medical risk factors/exposures. Results: We found positive family history and hypertension significantly linked to an increased breast cancer risk (adjusted O.R >1.5, 95% CI, P<0.05) whereas, intense physical activity, increased anthropometric measurements and breastfeeding per child in months were inversely associated with breast cancer risk (adjusted O.R <1.0, 95% CI, P<0.05) in our study cohort. Conclusion: Our study reaffirms contribution of established risk factors for breast cancer, highlights protective factors and necessitates awareness/screening programs to reduce breast cancer burden in upcoming generations. Continuous...

scholarly journals Potential of polygenic risk scores for improving population estimates of women’s breast cancer genetic risks

2021 ◽  
Author(s):  
Michael Wolfson ◽  
Steve Gribble ◽  
Nora Pashayan ◽  
Douglas F. Easton ◽  
Antonis C. Antoniou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Risk Stratification ◽  
Breast Cancer Incidence ◽  
Population Level ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Risk Algorithm

Abstract Purpose Breast cancer risk has conventionally been assessed using family history (FH) and rare high/moderate penetrance pathogenic variants (PVs), notably in BRCA1/2, and more recently PALB2, CHEK2, and ATM. In addition to these PVs, it is now possible to use increasingly predictive polygenic risk scores (PRS) as well. The comparative population-level predictive capability of these three different indicators of genetic risk for risk stratification is, however, unknown. Methods The Canadian heritable breast cancer risk distribution was estimated using a novel genetic mixing model (GMM). A realistically representative sample of women was synthesized based on empirically observed demographic patterns for appropriately correlated family history, inheritance of rare PVs, PRS, and residual risk from an unknown polygenotype. Risk assessment was simulated using the BOADICEA risk algorithm for 10-year absolute breast cancer incidence, and compared to heritable risks as if the overall polygene, including its measured PRS component, and PV risks were fully known. Results Generally, the PRS was most predictive for identifying women at high risk, while family history was the weakest. Only the PRS identified any women at low risk of breast cancer. Conclusion PRS information would be the most important advance in enabling effective risk stratification for population-wide breast cancer screening.

scholarly journals Family history of cancer in first degree relatives and risk of cancer of unknown primary

2021 ◽  
Author(s):  
Alexander L. R. Grewcock ◽  
Karlijn E. P. E. Hermans ◽  
Matty P. Weijenberg ◽  
Piet A. Brandt ◽  
Caroline Loef ◽  
...  
Keyword(s):  
Family History ◽  
Cancer Of Unknown Primary ◽  
Unknown Primary ◽  
Family History Of Cancer ◽  
First Degree Relatives ◽  
History Of ◽  
Risk Of Cancer ◽  
History Of Cancer

scholarly journals Risk of Cancer Following the Use of N-Nitrosodimethylamine (NDMA) Contaminated Ranitidine Products: A Nationwide Cohort Study in South Korea

2021 ◽  
Vol 10 (1) ◽  
pp. 153
Author(s):  
Hong Jin Yoon ◽  
Jie-Hyun Kim ◽  
Gi Hyeon Seo ◽  
Hyojin Park
Keyword(s):  
Cohort Study ◽  
Cancer Risk ◽  
South Korea ◽  
Primary Study ◽  
Study Cohort ◽  
Matched Cohort ◽  
Cancer Outcomes ◽  
H2 Receptor Antagonist ◽  
Carcinogenic Agent ◽  
Risk Of Cancer

N-nitrosodimethylamine (NDMA), a known carcinogenic agent, was recently detected in some products of ranitidine. Several studies have investigated the detectability of NDMA, in drugs and their risks. However, only a few epidemiological studies have evaluated cancer risk from the use of such individual drugs. This study investigates the risk of cancer in ranitidine users. We conducted an observational population-based cohort study using the Health Insurance Review and Assessment databases, which contain information about the use of medicines in South Korea. The primary study cohort consisted of ranitidine users (n = 88,416). For controls, we enrolled users of famotidine, another H2-receptor antagonist in which no NDMA has been detected. A 4:1 matched cohort was constructed to compare cancer outcomes of the two groups. Our matched cohort comprised of 40,488 ranitidine users and 10,122 famotidine users. There was no statistical difference in the overall cancer risk between the ranitidine and famotidine groups (7.45% vs. 7.56%, HR 0.99, 95% CI 0.91–1.07, p = 0.716). Additionally, no significant differences were observed in the analysis of 11 single cancer outcomes. We found no evidence that exposure to NDMA through ranitidine increases the risk of cancer.

Prediction of 10-year and lifetime risk of cancer in individual patients with established cardiovascular disease, results from UCC-SMART and CANTOS

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C.C Van 't Klooster ◽  
P.M Ridker ◽  
N.R Cook ◽  
J.G.J.V Aerts ◽  
J Westerink ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Lung Cancer ◽  
Cancer Risk ◽  
Prediction Models ◽  
Funding Source ◽  
Cancer Models ◽  
Total Cancer ◽  
The Cantos ◽  
Risk Of Cancer

Abstract Background As treatment for cardiovascular disease (CVD) has improved substantially over the last decades, more patients survive acute CVD manifestations and are at risk for developing cancer as well as recurrent CVD. Due to similar risk factors, including smoking and obesity, patients with established CVD are at higher risk for cancer. Objectives The aim of this study was to develop and externally validate prediction models for the estimation of 10-year and lifetime risk for total, colorectal, and lung cancer in patients with established CVD. Methods Data from patients with established CVD from the UCC-SMART prospective cohort study (N=7,280) were used for model development, and data from the CANTOS trial (N=9,322) were used for model validation. Predictors were selected based on previously published cancer risk prediction models or cancer risk factors, easy clinical availability, and availability in the derivation dataset (UCC-SMART cohort). A Fine and Gray competing risk-adjusted lifetime model was developed for total, colorectal, and lung cancer. Results Selected predictors were age, sex, smoking status, weight, height, alcohol use, antiplatelet use, diabetes mellitus, and C-reactive protein. External calibration for 4-year risks of the total cancer, colorectal cancer, and lung cancer models was good (Figure 1), and C-statistics were 0.63–0.74 in the CANTOS trial population. Median predicted lifetime risks in CANTOS were 26% (range 1%-52%) for total cancer, 4% (range 0%-13%) for colorectal cancer, and 5% (range 0%-37%) for lung cancer. Conclusions Lifetime and 10-year risk of cancer can be estimated with easy to measure variables in patients with established CVD, showing a wide distribution of predicted lifetime risks for total cancer and lung cancer. Using these lifetime models in clinical practice could increase understanding of cancer risk and aid in emphasizing healthy lifestyle changes. Figure 1. Calibration plots of cancer models Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): University Medical Center; Additional funding: CANTOS trial was funded by Novartis Pharmaceuticals.

scholarly journals Blood Pressure Trajectories Across the Life Course

2021 ◽  
Vol 34 (3) ◽  
pp. 234-241
Author(s):  
Norrina B Allen ◽  
Sadiya S Khan
Keyword(s):  
Blood Pressure ◽  
Measurement Errors ◽  
Clinical Care ◽  
Population Level ◽  
Cumulative Exposure ◽  
Older Adulthood ◽  
Individual Level ◽  
The Life Course ◽  
Level Group ◽  
Improve Health

Abstract High blood pressure (BP) is a strong modifiable risk factor for cardiovascular disease (CVD). Longitudinal BP patterns themselves may reflect the burden of risk and vascular damage due to prolonged cumulative exposure to high BP levels. Current studies have begun to characterize BP patterns as a trajectory over an individual’s lifetime. These BP trajectories take into account the absolute BP levels as well as the slope of BP changes throughout the lifetime thus incorporating longitudinal BP patterns into a single metric. Methodologic issues that need to be considered when examining BP trajectories include individual-level vs. population-level group-based modeling, use of distinct but complementary BP metrics (systolic, diastolic, mean arterial, mid, and pulse pressure), and potential for measurement errors related to varied settings, devices, and number of readings utilized. There appear to be very specific developmental periods during which divergent BP trajectories may emerge, specifically adolescence, the pregnancy period, and older adulthood. Lifetime BP trajectories are impacted by both individual-level and community-level factors and have been associated with incident hypertension, multimorbidity (CVD, renal disease, cognitive impairment), and overall life expectancy. Key unanswered questions remain around the additive predictive value of BP trajectories, intergenerational contributions to BP patterns (in utero BP exposure), and potential genetic drivers of BP patterns. The next phase in understanding BP trajectories needs to focus on how best to incorporate this knowledge into clinical care to reduce the burden of hypertensive-related outcomes and improve health equity.

scholarly journals The Association of Nighttime Fasting Duration and Prostate Cancer Risk: Results from the Multicase-Control (MCC) Study in Spain

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2662
Author(s):  
Anna Palomar-Cros ◽  
Ana Espinosa ◽  
Kurt Straif ◽  
Beatriz Pérez-Gómez ◽  
Kyriaki Papantoniou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Lower Risk ◽  
Night Shift ◽  
Prostate Cancer Risk ◽  
Meal Timing ◽  
Risk Of Cancer ◽  
Fasting Duration ◽  
Population Controls ◽  
Reduced Risk

Nighttime fasting has been inconclusively associated with a reduced risk of cancer. The purpose of this study was to investigate this association in relation to prostate cancer risk. We examined data from 607 prostate cancer cases and 848 population controls who had never worked in night shift work from the Spanish multicase-control (MCC) study, 2008–2013. Through an interview, we collected circadian information on meal timing at mid-age. We estimated odds ratios (OR) and 95% confidence intervals (CI) with unconditional logistic regression. After controlling for time of breakfast, fasting for more than 11 h overnight (the median duration among controls) was associated with a reduced risk of prostate cancer compared to those fasting for 11 h or less (OR = 0.77, 95% 0.54–1.07). Combining a long nighttime fasting and an early breakfast was associated with a lower risk of prostate cancer compared to a short nighttime fasting and a late breakfast (OR = 0.54, 95% CI 0.27–1.04). This study suggests that a prolonged nighttime fasting duration and an early breakfast may be associated with a lower risk of prostate cancer. Findings should be interpreted cautiously and add to growing evidence on the importance of chrononutrition in relation to cancer risk.

scholarly journals Diabetes, Antidiabetic Medications and Cancer Risk in Type 2 Diabetes: Focus on SGLT-2 Inhibitors

2021 ◽  
Vol 22 (4) ◽  
pp. 1680
Author(s):  
Mariusz Dąbrowski
Keyword(s):  
Type 2 Diabetes ◽  
Cancer Risk ◽  
The European Union ◽  
Sodium Glucose Cotransporter ◽  
Incidence And Mortality ◽  
Increasing Risk ◽  
Risk Of Cancer ◽  
Diabetes And Obesity ◽  
Increased Activity

In the last decade, cancer became the leading cause of death in the population under 65 in the European Union. Diabetes is also considered as a factor increasing risk of cancer incidence and mortality. Type 2 diabetes is frequently associated with being overweight and obese, which also plays a role in malignancy. Among biological mechanisms linking diabetes and obesity with cancer hyperglycemia, hyperinsulinemia, insulin resistance, increased levels of growth factors, steroid and peptide hormones, oxidative stress and increased activity of pro-inflammatory cytokines are listed. Antidiabetic medications can modulate cancer risk through directly impacting metabolism of cancer cells as well as indirectly through impact on risk factors of malignancy. Some of them are considered beneficial (metformin and thiazolidinedions—with the exception of bladder cancer); on the other hand, excess of exogenous insulin may be potentially harmful, while other medications seem to have neutral impact on cancer risk. Inhibitors of the sodium-glucose cotransporter-2 (SGLT-2) are increasingly used in the treatment of type 2 diabetes. However, their association with cancer risk is unclear. The aim of this review was to analyze the anticancer potential of this class of drugs, as well as risks of site-specific malignancies associated with their use.

Sign in / Sign up

Export Citation Format

Share Document