Referral of early onset renal cell carcinoma for clinical cancer genetic assessment.

613 Background: Approximately 1-8% of renal cell carcinomas (RCCs) are associated with inherited predisposition. No consensus referral guideline exists for genetic assessment for RCC. Early age of onset, the presence of a family history and type II papillary RCC should trigger clinical genetics referral. We investigated the pattern of cancer genetics referral for early-onset RCC in Ireland. Methods: The number of patients with RCC diagnosed under the age of 50 between 2005 and 2013, was obtained from the National Cancer Registry of Ireland. RCC was defined by the WHO/IARC Classification. The number of patients referred for genetic work-up with RCC < 50 years of age was ascertained from The National Centre for Medical Genetics. Individuals unaffected by RCC but with a family history of RCC were excluded. The database was searched using the following search terms: Von Hippel-Lindau (VHL), Birt-Hogg-Dube (BHD) and RCC; and the clinical reason for referral recorded. Results: 580 patients were diagnosed with RCC below the age of 50. 71 percent were between 40 and 49 years of age (n=410). 52 patients were referred to The National Centre for Medical Genetics. Indications for referral are listed in Table 1. 7 patients were referred for a diagnosis of RCC < 50 years of age. The average age of these patients was 37.8 years. Three of the referrals were for early age of onset of RCC; two referrals were made for early age of onset with a family history of RCC; and two with early onset RCC and bilateral RCCs. This represents a referral rate of approximately 0.01% for early onset RCC in Ireland. Conclusions: Most early onset RCC is not referred for clinical cancer genetics assessment. The heritability of RCC is incompletely understood. Improved referral patterns, increased clinical genetics assessment and a better understanding of the genetic aetiology of RCC may have preventive and therapeutic implications for this disease. [Table: see text]

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Oesophageal cancer: Commonly familial, possibly heritable.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.23 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 23-23

Author(s):

Niamh Peters ◽

Sinead King ◽

Emily O'Donovan ◽

David James Gallagher ◽

John V Reynolds

Keyword(s):

Family History ◽

Oesophageal Cancer ◽

Cancer Genetics ◽

Age At Diagnosis ◽

Degree Relative ◽

Genetic Database ◽

The Family ◽

History Of ◽

Oesophageal Surgery ◽

Genetic Assessment

23 Background: Oesophageal cancer (OC) accounts for 400 deaths in Ireland per year. Prognosis remains poor, and improved prevention is needed. Familial clustering has been described however, The Nordic Twin Study of Cancer does not support a strong hereditability. We investigated familial OC over a decade in Ireland. Methods: The independent records of two national referral services were reviewed: an oesophageal surgery database and a hereditary cancer genetics database. Demographic Factors including family history of OC were recorded from the surgical database. Families containing a single OC diagnosis were identified in the genetics database. Age at diagnosis and additional cancer diagnoses in the family were recorded. Results: 1238 patients with OC were seen at St. James’s Hospital from 2005 to 2015. Demographic characteristics are shown in Table. 641 patients (51%) had a family history of malignancy. Seventy eight (6.3%) reported a family history of OC, 6 (7.6%) of whom had two or more first degree relatives with OC and 10 (13%) had both a first degree and second degree relative with OC. More male relatives were diagnosed with OC than female (59% vs 41%).The majority (24%) with a family history were diagnosed at Stage III, the majority (29%) without a family history were diagnosed at Stage II. 1840 pedigrees from the genetic database were reviewed. No pedigree contained a Proband with OC.4.5%(n = 84) included at least one family member with OC. The median age at diagnosis was 64. Breast, colorectal and gastric were the most commonly associated cancers with median ages of 50,59 and 64 respectively. Conclusions: More than half of patients presenting with OC report a family history of cancer, with likely hereditary and environmental components. OC patients are rarely referred for genetic assessment, possibly due to treatment related morbidity and poor clinical outcome. [Table: see text]

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Hereditary Susceptibility to Breast Cancer: Significance of Age of Onset in Family History and Contribution of BRCA1 and BRCA2

Disease Markers ◽

10.1155/1999/291023 ◽

1999 ◽

Vol 15 (1-3) ◽

pp. 89-92 ◽

Cited By ~ 14

Author(s):

Thomas S. Frank ◽

Amie M. Deffenbaugh ◽

Mark Hulick ◽

Kathryn Gumpper

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Family History ◽

Early Onset ◽

Age Of Onset ◽

Early Onset Breast Cancer ◽

Brca1 And Brca2 ◽

Degree Relative ◽

Age Of Diagnosis ◽

History Of

OBJECTIVE: To correlate mutations in BRCA1 and BRCA2 with family history of breast cancer in a first-degree relative for women diagnosed with breast cancer before age 45 who do not have a personal or family history of ovarian cancer.METHODS: Family history for women with breast cancer diagnosed before age 45 was provided by ordering physicians via a test requisition form designed for this purpose. Gene analysis was performed by dye primer sequencing for the entire coding regions of BRCA1 and BRCA2. Because a personal and family history of ovarian cancer are known to be significantly associated with mutations, women with either were excluded from analysis.RESULTS: Overall, deleterious mutations in BRCA1 or BRCA2 were identified in 85 of 440 women (19%) with breast cancer under 45. Mutations were identified in 73 of 276 women (26%) with a first degree family history of breast cancer compared to 12 of 164 without (7%) (P <.0001). When results were analyzed by the age of diagnosis in first degree relatives, mutations were identified in 56 of 185 women (30%) with at least one first degree relative with breast cancer diagnosed before age 50 compared with 17 of 91 women (19%), where the first degree family history of breast cancer was at or over age 50 (P = .042).CONCLUSION: Among women with breast cancer diagnosed before age 45, a first-degree relative diagnosed with the disease under age 50 is an indicator of a mutation in BRCAl or BRCA2 even in the absence of a family history of ovarian cancer. Therefore, women diagnosed with early-onset breast cancer should be asked about the age of onset in any first-degree relative diagnosed with the disease, as well as about any family history of ovarian cancer. Mutations in BRCA2 account for a substantial proportion of hereditary breast cancer. Therefore, studies that are limited to BRCA1 or that do not analyze by age of onset of breast cancer in relatives may underestimate the contribution of mutations in BRCAl and BRCA2 to women with early onset breast cancer.

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Response to drugs in schizophrenia: the influence of family history, obstetric complications and ventricular enlargement

Psychological Medicine ◽

10.1017/s0033291700008266 ◽

1988 ◽

Vol 18 (3) ◽

pp. 583-592 ◽

Cited By ~ 25

Author(s):

V. L. Nimgaonkar ◽

S. Wessely ◽

L. E. Tune ◽

R. M. Murray

Keyword(s):

Family History ◽

Prospective Study ◽

Age Of Onset ◽

Obstetric Complications ◽

Early Age ◽

Ventricular Enlargement ◽

Familial Predisposition ◽

History Of ◽

A Prospective Study ◽

Antipsychotic Drug Treatment

SynopsisA prospective study of antipsychotic drug treatment showed no difference in response between schizophrenic in-patients with or without a familial predisposition to the illness (N = 53). All patients received at least 600 mg chlorpromazine equivalents antipsychotic medication for 6 weeks. Ventricle brain ratios, ratings of cortical sulcal widening and a history of obstetric complications also failed to account for the variability, but early age of onset was associated with unsatisfactory response.

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Clinical, Pathological and Molecular Characteristics of Chilean Patients with Early-, Intermediate- and Late-Onset Colorectal Cancer

Cells ◽

10.3390/cells10030631 ◽

2021 ◽

Vol 10 (3) ◽

pp. 631

Author(s):

Karin Alvarez ◽

Alessandra Cassana ◽

Marjorie De La Fuente ◽

Tamara Canales ◽

Mario Abedrapo ◽

...

Keyword(s):

Colorectal Cancer ◽

Family History ◽

Age Of Onset ◽

Late Onset ◽

Molecular Characteristics ◽

Family History Of Cancer ◽

Molecular Features ◽

Age Of Diagnosis ◽

History Of ◽

History Of Cancer

Colorectal cancer (CRC) is the second most frequent neoplasm in Chile and its mortality rate is rising in all ages. However, studies characterizing CRC according to the age of onset are still lacking. This study aimed to identify clinical, pathological, and molecular features of CRC in Chilean patients according to the age of diagnosis: early- (≤50 years; EOCRC), intermediate- (51–69 years; IOCRC), and late-onset (≥70 years; LOCRC). The study included 426 CRC patients from Clinica Las Condes, between 2007 and 2019. A chi-square test was applied to explore associations between age of onset and clinicopathological characteristics. Body Mass Index (BMI) differences according to age of diagnosis was evaluated through t-test. Overall (OS) and cancer-specific survival (CSS) were estimated by the Kaplan–Meier method. We found significant differences between the age of onset, and gender, BMI, family history of cancer, TNM Classification of Malignant Tumors stage, OS, and CSS. EOCRC category was characterized by a family history of cancer, left-sided tumors with a more advanced stage of the disease but better survival at 10 years, and lower microsatellite instability (MSI), with predominant germline mutations. IOCRC has shown clinical similarities with the EOCRC and molecular similarities to the LOCRC, which agrees with other reports.

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Season of birth interacts with measures of inbreeding in multiplex schizophrenia pedigrees: evidence from genetic isolates in Daghestan

Open Medicine ◽

10.2478/s11536-006-0041-8 ◽

2006 ◽

Vol 1 (4) ◽

pp. 392-398

Author(s):

Kazima Bulayeva ◽

John McGrath

Keyword(s):

Genetic Diversity ◽

Family History ◽

Age Of Onset ◽

Population Genetic Study ◽

Season Of Birth ◽

High Genetic Diversity ◽

Low Genetic Diversity ◽

High Prevalence ◽

History Of ◽

Genetic Isolates

AbstractWhile the season-of-birth effect is one of the most consistent epidemiological features of schizophrenia, there is a lack of consistency with respect to the interaction between season of birth and family history of schizophrenia. Apart from family history, measures related to consanguinity can be used as proxy markers of genomic heterogeneity. Thus, these measures may provide an alternate, indirect index of genetic susceptibility. We had the opportunity to explore the interaction between season of birth and measure of consanguinity in well-described genetic isolates in Daghestan, some of which are known for their relatively high prevalence of schizophrenia. Our previous population-genetic study showed Daghestan has an extremely high genetic diversity between the ethnic populations and a low genetic diversity within them. The isolates selected for this study include some with more than 200 and some with less than 100 generations of demographical history since their founding. Based on pedigrees of multiply-affected families, we found that among individuals with schizophrenia, the measure of consanguinity was significantly higher in the parents of those born in winter/spring compared to those born in summer/autumn. Furthermore, compared to summer/autumn born, winter/spring born individuals with schizophrenia had an earlier age-of-onset, and more prominent auditory hallucinations. Our results suggest that the offspring of consanguineous marriages, and thus those with reduced allelic heterogeneity, may be more susceptible to the environmental factor(s) underpinning the season-of-the effect in schizophrenia.

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Association of Androgenetic Alopecia with Benign Prostatic Hyperplasia: A Case Control Study

Nepal Journal of Dermatology Venereology & Leprology ◽

10.3126/njdvl.v16i1.19399 ◽

2018 ◽

Vol 16 (1) ◽

pp. 17-23

Author(s):

Manoj Kumar Chaudhary ◽

Sudha Agrawal ◽

Chandra Shekhar Agrawal

Keyword(s):

Benign Prostatic Hyperplasia ◽

Family History ◽

Early Onset ◽

Positive Family History ◽

Prostatic Hyperplasia ◽

Androgenetic Alopecia ◽

Pelvic Ultrasonography ◽

Increased Risk ◽

History Of ◽

Common Pathogenesis

Introduction: Androgenetic alopecia (AGA) is associated with increased risk of several systemic diseases and some environmental factors, however, controversies exist. Since AGA and Benign Prostatic Hyperplasia (BPH) share common pathogenesis and AGA manifests some decades before BPH onset, it may serve as an early marker of BPH.Objective: This study was conducted to know AGA and its association with BPH in men ≥20 years of age.Materials and Methods: Clinically diagnosed cases of AGA (n=176) and 117 age matched healthy controls were enrolled. All cases and controls were subjected for abdomino-pelvic ultrasonography, urinary flowmetry, fasting lipid profiles, glycemic index and body mass index. International Prostate Symptom Score (IPSS) was also assessed.Results: Among 176 patients, 120 (68.18%) had Hamilton-Norwood grade III AGA and 56 (31.82%) had grade IV-VII AGA. In both groups, 140 (79.55%) cases and 93 (79.49%) controls were aged <35 years respectively. Family history of AGA was present in 108 (61.36%) cases and 2 (1.71%) controls. This observation was statistically significant with OR= 89.61 (95%CI 23.67-339.29). Three (1.7%) cases and none of the controls had prostate volume >30ml. Seventeen(9.66%) cases and 4 (3.42%) controls were graded as moderately/severely symptomatic IPSS. Statistically significant association was seen between family history and early onset of hair loss (<35 years) in a male sibling or parent.Conclusion: Although positive family history was associated with early onset of AGA, no association between AGA and BPH could be elicited in our study.

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The Characteristics of Risk Factors in Chinese Young Women with Acute Coronary Syndrome

10.21203/rs.3.rs-19763/v1 ◽

2020 ◽

Author(s):

Ruifang Liu ◽

Fangxing Xu ◽

Yujie Zhou ◽

Tongku Liu

Keyword(s):

Risk Factors ◽

Family History ◽

Young Women ◽

Early Onset ◽

Young Female ◽

Cardiac Insufficiency ◽

Control Group ◽

Significant Difference ◽

Gynecological Diseases ◽

History Of

Abstract Background In recent years, the prevalence rate of ACS in Chinese young women has been increasing significantly, becoming the main cause of death in young female. This study aimed to investigate the characteristics and difference of risk factors in Chinese young women with ACS and to provide references for ACS prevention and treatment. Methods A 1:1 case-control study was conducted to evaluate risk factors of 415 young female patients with ACS (ACS group) who underwent PCI treatment and 415 young female cases without ACS (control group) who were hospitalized and confirmed by coronary angiography to exclude coronary heart disease from January 2010 to August 2016. The average age of the cases in the two groups was respectively (40.77±4.02) years-old and (40.57±4.01) years-old (P> 0.05). Results The risk factors in ACS group were overweight (64.10%), hypertension (49.88%), hyperlipidemia (35.66%), diabetes (23.37%), depression or anxiety disorder (16.62%), gynecological diseases (16.39%), Hyperuricemia (15.18%), family history of early onset coronary heart disease (14.94%), hyperhomocysteinemia (11.33%), hypothyroidism(14.96%), hypercholesterolemia (8.43%) and high c-reactive protein (7.47%), and were statistically significant difference (P<0.01) compared with that of control group. The average number of risk factors per case in ACS group was significantly more than that of control groups (P<0.01). There was a statistically significant difference in the number of combined risk factors of the overweight cases compared between two groups (P<0.01). Regression analysis showed that hyperlipidemia, hyperhomocysteinemia, overweight（obesity）, high CRP, hypertension, hypothyroidism, gynecological diseases, depression or anxiety, cardiac insufficiency, hypercholesterolemia, diabetes, oral contraceptives, family history of early onset CHD, and autoimmune diseases were independent risk factors (P<0.01). The bivariate correlation analysis between CRP level and age was r= -0.158 (P<0.01). This result showed the younger ACS patient is the higher serum CRP. Conclusion The independent risk factors of ACS in young women are hyperlipidemia, hyperhomocysteinemia, overweight, high CRP, hypertension, hypothyroidism, gynecological diseases, depression or anxiety, cardiac insufficiency, hypercholesterolemia, diabetes, oral contraceptives, family history of early onset CHD, and autoimmune diseases. The co-existence of multiple risk factors is the main cause suffering from ACS in young women.

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Clinical, epidemiological and autoimmune associations in childhood vitiligo in Qatar

International Journal of Research in Dermatology ◽

10.18203/issn.2455-4529.intjresdermatol20200594 ◽

2020 ◽

Vol 6 (2) ◽

pp. 151

Author(s):

Haya Al Mannai ◽

Mohamed Allam ◽

Hassan Riad

Keyword(s):

Family History ◽

Autoimmune Diseases ◽

Age Of Onset ◽

Positive Family History ◽

Thyroid Peroxidase ◽

Base Line ◽

Adult Onset ◽

Prognostic Features ◽

History Of ◽

The Mean

Background: Childhood vitiligo although clinically similar to adult onset vitiligo but it has distinct clinical, epidemiological and prognostic features compared to adult onset vitiligo.Methods: This is a retrospective study that was carried out on 85 pediatric patients up to age of 18 years old with the diagnosis of vitiligo, where the clinical and epidemiological data including clinical type of vitiligo, family history of autoimmune diseases like thyroid disorders and diabetes mellitus and laboratory results including anti-thyroid peroxidase antibodies (anti-TPO antibodies), anti-parietal cell antibodies, antinuclear antibodies (ANA), Vitamin D and Vitamin B12 were retrieved from the files of these patients.Results: The mean age of the children affected by vitiligo was 10.4 years, the mean age of onset of vitiligo was 5.4 years, 54 (63.5%) percent were girls and 31 (36.5%) were boys. A positive family history of vitiligo was found in 44.7% of the participants, family history of DM was found in 64.7% of patients and family history of thyroid disease was found in 32.9% of the participants. The prevalence of thyroid autoimmunity was found to be in 22.4% of total participants.Conclusions: Childhood vitiligo has distinct clinical features, more common family history for autoimmune diseases and thyroid autoantibodies rather than overt clinical diseases, which raise the necessity to perform a routine initial immunological and thyroid screening in children with vitiligo and to repeat them at annual bases if there were abnormal values at base line or strong family history.

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