High Risk Indicators: Microscopic Lesions, Personal and Family History, Assessment, and Management

No single parameter or combination of parameters seemed suitable for general screening. However, a combination of family history, assessment of skin dryness, and cord blood IgE could be used to identify newborns at high risk of allergy for participation in prevention studies.

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

Genome Medicine ◽

10.1186/s13073-020-00819-1 ◽

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.

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658 An Audit of Frequency of Cancer Genetics Referral in Patients with a Family History of Colorectal Cancer

British Journal of Surgery ◽

10.1093/bjs/znab134.464 ◽

2021 ◽

Vol 108 (Supplement_2) ◽

Author(s):

M Abbakar ◽

T James ◽

P Boxall ◽

M Lim

Keyword(s):

Family History ◽

High Risk ◽

Hereditary Cancer ◽

Risk Category ◽

Average Risk ◽

Insufficient Data ◽

High Risk Patients ◽

Amsterdam Criteria ◽

Family History Questionnaire ◽

Risk Patients

Abstract Introduction Guidelines on the management of hereditary colorectal cancers were updated in 2019. In this study, data from patients within the colonoscopy surveillance programme for hereditary cancer at York Teaching Hospitals Trust were analysed to assess category of risk and appropriateness of referrals to regional geneticists. Method After examination of electronic records and clinical notes, patients were assigned a risk category of average, moderate or high according to the Amsterdam criteria and latest BSG/ACPGBI/UKCGG guidelines. Patients were then assessed to see if a concurrent referral had been made to the regional cancer genetic services. Results There were 228 patients. 72(31.6%) patients were in the average, 81(35.5%) in the moderate and 41(18%) were in the high-risk category. 34 (14.9%) patients with insufficient data and/or assessments were in the indeterminate category. 18 of 72 (25%) patients with average risk were unnecessarily referred to the regional genetics team, while 5/41(12%) of high-risk patients were not. A large proportion of patients with insufficient data (19/34, 55.8%) were rightly or wrongly, referred to the regional genetics team. Conclusions Assessment of hereditary cancer risk is difficult in the absence of good quality information. Risk assessment may be improved with use of a dedicated family history questionnaire/template - this facilitates identification of high-risk patients that benefit most from referral to geneticists.

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Cancer Previvors in an Active Duty Service Women Population: An Opportunity for Prevention and Increased Force Readiness

Military Medicine ◽

10.1093/milmed/usaa485 ◽

2020 ◽

Author(s):

Leann A Lovejoy ◽

Clesson E Turner ◽

Craig D Shriver ◽

Rachel E Ellsworth

Keyword(s):

Genetic Testing ◽

Family History ◽

High Risk ◽

Cancer Predisposition ◽

Clinical Genetic ◽

High Risk Women ◽

Clinical Genetic Testing ◽

Pathogenic Mutations ◽

History Of ◽

Risk Reducing

Abstract Background The majority of active duty service women (ADS) are young, have access to healthcare, and meet fitness standards set by the U.S. military, suggesting that ADS represent a healthy population at low risk of cancer. Breast cancer is, however, the most common cancer in ADS and may have a significant effect on troop readiness with lengthy absence during treatment and inability to return to duty after the treatment. The identification of unaffected ADS who carry germline mutations in cancer predisposition genes (“previvors”) would provide the opportunity to prevent or detect cancer at an early stage, thus minimizing effects on troop readiness. In this study, we determined (1) how many high-risk ADS without cancer pursued genetic testing, (2) how many previvors employed risk-reducing strategies, and (3) the number of undiagnosed previvors within an ADS population. Methods The Clinical Breast Care Project (protocol WRNMMC IRB #20704) database of the Murtha Cancer Center/Walter Reed National Military Medical Center was queried to identify all ADS with no current or previous history of cancer. Classification as high genetic risk was calculated using National Comprehensive Cancer Network 2019 guidelines for genetic testing for breast, ovary, colon, and gastric cancer. The history of clinical genetic testing and risk-reducing strategies was extracted from the database. Genomic DNA from ADS with blood specimens available for research purposes were subjected to next-generation sequencing technologies using a cancer predisposition gene panel. Results Of the 336 cancer-free ADS enrolled in the Clinical Breast Care Project, 77 had a family history that met National Comprehensive Cancer Network criteria for genetic testing for BRCA1/2 and 2 had a family history of colon cancer meeting the criteria for genetic testing for Lynch syndrome. Of the 28 (35%) high-risk women who underwent clinical genetic testing, 11 had pathogenic mutations in the breast cancer genes BRCA1 (n = 5), BRCA2 (n = 5), or CHEK2 (n = 1). Five of the six ADS who had a relative with a known pathogenic mutation were carriers of the tested mutation. All of the women who had pathogenic mutations detected through clinical genetic testing underwent prophylactic double mastectomy, and three also had risk-reducing salpingo-oophorectomy. Two (6%) of the 33 high-risk ADS tested only in the research setting had a family history of breast/ovarian cancer and carried pathogenic mutations: one carried a BRCA2 mutation, whereas the other carried a mutation in the colon cancer predisposition gene PMS2. No mutations were detected in the 177 low-risk women tested in the research setting. Discussion Within this unaffected cohort of ADS, 23% were classified as high risk. Although all of the previvors engaged in risk-reduction strategies, only one-third of the high-risk women sought genetic testing. These data suggest that detailed family histories of cancer should be collected in ADS and genetic testing should be encouraged in those at high risk. The identification of previvors and concomitant use of risk-reduction strategies may improve health in the ADS and optimize military readiness by decreasing cancer incidence.

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Colorectal Cancer Family History Assessment

Clinical Journal of Oncology Nursing ◽

10.1188/11.cjon.e75-e82 ◽

2011 ◽

Vol 15 (5) ◽

pp. E75-E82 ◽

Cited By ~ 7

Author(s):

Patricia Paul Kelly

Keyword(s):

Colorectal Cancer ◽

Family History ◽

Cancer Family ◽

Cancer Family History ◽

Family History Assessment

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Iodine status and its determinants in subpopulation of pregnant women in rural Central India

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20180191 ◽

2018 ◽

Vol 7 (2) ◽

pp. 665

Author(s):

Surekha A. Tayade ◽

Shakuntala Chhabra

Keyword(s):

Family History ◽

High Risk ◽

Pregnant Women ◽

Iodine Deficiency ◽

Tertiary Care ◽

Central India ◽

Iodized Salt ◽

High Risk Population ◽

Iodine Status ◽

Rich Food

Background: There is an increased demand for iodine and thyroid hormones, in pregnancy starting from the early weeks of pregnancy suggesting that there may be a need for additional supplements of iodine in high risk population to prevent iodine deficiency and its associated disorders. Hence this study was undertaken to determine the iodine status and its determinants in a subpopulation of pregnant women from a rural area of Central India.Methods: A hospital based, cross-sectional, observational study was carried out among pregnant women seeking antenatal care at Kasturba Hospital of MGIMS, Sewagram, a rural tertiary care institute in central India. Information was collected about demographic variables, use of iodized salt, iodine rich food and goitrogens as part of diet and other determinants. Spot urine samples were obtained, and assessment of urine iodine concentration was done by using Sandell-Kolthoff reaction.Results: Among 250 pregnant women of first trimester, iodine deficiency (ID) was present in 11.8 %, of which 59.25% had mild deficiency, 33.33% moderate deficiency and 7.4% severe deficiency. More women with iodine deficiency were of higher age, had less formal education and belonged to lower middle and lower economic class. Higher number of women with iodine deficiency had family history of thyroid disorders compared to iodine sufficient (18.51% versus 5.58%), more iodine deficient commonly had goitrogens (cabbage, cauliflower, radish, sweet potato, soya etc) as part of their meals (77.77% versus 68.60%), lesser women with ID ate iodine rich food (fish, milk yoghurt, bread) (18.51% versus 68.60%) and fewer of them used iodized salt during food preparation (25.92% versus 69.95%) compared to iodine sufficient, with a significant difference.Conclusions: Iodine deficiency is prevalent in pregnant women in this geographic region of central India. Age, low socioeconomic status, lack of education, family history, low intake of iodized salt and iodine rich food and more consumption of goitrogenic food as part of diet are risk factors. Appropriate health education, promoting use of iodized salt, quality assurance of universal salt iodization by household survey and screening in high risk group is suggested.

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Prostate cancer screening characteristics in men with BRCA1/2 mutations attending a high-risk prevention clinic

Canadian Urological Association Journal ◽

10.5489/cuaj.1970 ◽

2014 ◽

Vol 8 (11-12) ◽

pp. 783 ◽

Cited By ~ 3

Author(s):

Richard Walker ◽

Alyssa Louis ◽

Alejandro Berlin ◽

Sheri Horsburgh ◽

Robert G. Bristow ◽

...

Keyword(s):

Prostate Cancer ◽

Family History ◽

High Risk ◽

Prostate Cancer Screening ◽

Brca2 Mutation ◽

Aggressive Disease ◽

Mutation Carriers ◽

The Family ◽

History Of ◽

Prevention Clinic

Introduction: The prostate-specific antigen (PSA) era and resultant early detection of prostate cancer has presented clinicians with the challenge of distinguishing indolent from aggressive tumours. Mutations in the BRCA1/2 genes have been associated with prostate cancer risk and prognosis. We describe the prostate cancer screening characteristics of BRCA1/2 mutation carriers, who may be classified as genetically-defined high risk, as compared to another high-risk cohort of men with a family history of prostate cancer to evaluate the utility of a targeted screening approach for these men.Methods: We reviewed patient demographics, clinical screening characteristics, pathological features, and treatment outcomes between a group of BRCA1 or BRCA2 mutation carriers and age-matched men with a family history of prostate cancer followed at our institutional Prostate Cancer Prevention Clinic from 1995 to 2012.Results: Screening characteristics were similar between the mutation carriers (n = 53) and the family history group (n = 53). Some cancers would be missed in both groups by using a PSA cut-off of >4 ug/L. While cancer detection was higher in the family history group (21% vs. 15%), the mutation carrier group was more likely to have intermediate- or high-risk disease (88% vs. 36%). BRCA2 mutation carriers were more likely to have aggressive disease, biological recurrence, and distant metastasis.Conclusions: In our cohort, regular screening appears justified for detecting prostate cancer in BRCA1 and BRCA2 carriers and other high-risk populations. Lowering PSA cut-offs and defining monitoring of PSA velocity as part of the screening protocol may be useful. BRCA2 is associated with more aggressive disease, while the outcome for BRCA1 mutation carriers requires further study. Large multinational studies will be important to define screening techniques for this unique high-risk population.

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