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Familial Cancer Oct 2016Multiple endocrine neoplasia type 2A (MEN2A) may be rarely associated with cutaneous lichen amyloidosis (CLA), a skin lesion located in the interescapular region. Here,... (Review)
Review
Multiple endocrine neoplasia type 2A (MEN2A) may be rarely associated with cutaneous lichen amyloidosis (CLA), a skin lesion located in the interescapular region. Here, we describe 3 MEN2A-related CLA kindred and perform a systematic review (SR) of the literature on clinical, biochemical and molecular characteristics of MEN2A-related CLA patients. Thirty-eight patients with MEN2A-related CLA followed at our institution were evaluated. The median age at MEN2A diagnosis in our cohort was 25 (13-41) years, 68 % were women and all harbored codon 634 RET mutations. The literature search resulted in 20 publications that contributed with 25 MEN2A families and 214 individuals. The mean age of MEN2A diagnosis was 31 ± 17 years, with 77 % women. The mean age reported by patients to initial skin lesion suggestive to CLA was 20 ± 13 years. All but two kindred harbored mutations at codon 634: C634R 7 kindred (35 %), C634Y 5 kindred (25 %), C634W 3 kindred (15 %), C634G 1 kindred (5 %), V804M 1 kindred (5 %) and S891A 1 kindred (5 %). Most interesting, the standardized CLA prevalence was higher in women (2.3/1.0, P < 0.005). The overall reported prevalence of medullary thyroid carcinoma, CLA, pheochromocytoma and hyperparathyroidism was 94, 51, 30 and 16 %, respectively. SR of literature indicates that MEN2A-related CLA is more frequent in women and presents a high penetrance, being the second most frequent manifestation of the syndrome, preceded only by MTC.
Topics: Adolescent; Adult; Amyloidosis; Female; Humans; Male; Multiple Endocrine Neoplasia Type 2a; Pedigree; Proto-Oncogene Proteins c-ret; Skin Neoplasms; Young Adult
PubMed: 26920351
DOI: 10.1007/s10689-016-9892-6 -
JAMA Neurology Jul 2020Genetic and environmental factors are thought to contribute to cluster headache, and cluster headache can affect multiple members of a family. A thorough understanding...
IMPORTANCE
Genetic and environmental factors are thought to contribute to cluster headache, and cluster headache can affect multiple members of a family. A thorough understanding of its inheritance is critical to understanding the pathogenesis of this debilitating disease.
OBJECTIVE
To systematically review family history rates and inheritance patterns of cluster headache.
EVIDENCE REVIEW
A systematic review was performed in PubMed, Embase, and Cochrane Library. Search criteria were created by a librarian. Articles published between 1985 and 2016, after the publication date of a large review in 1985, were analyzed independently by 2 neurologists to identify family history rates and pedigrees. Pedigrees were analyzed by a genetic counselor.
FINDINGS
A total of 1995 studies were found (1988 through the search criteria and 7 through other means). Forty articles met inclusion criteria: 22 large cohort studies, 1 twin-based study, and 17 case reports or small case series. Across the 22 large cohort studies, the positive family history rate of cluster headache varied between 0% and 22%, with a median of 8.2%. The largest 5 studies, of 1134, 785, 693, 609, and 500 probands each, had a positive family history in 18.0% (numerator not provided), 5.1% (40 of 785 cases), 10.0% (numerator not provided), 2.0% (12 of 609 cases), and 11.2% (56 of 500 cases), respectively. No meta-analysis was performed, given differences in methodologies. Separately, 1 twin-based study examined 37 twin pairs and reported a concordance rate of 5.4% (2 pairs). Finally, 67 pedigrees were identified. Most pedigrees (46 of 67 [69%]) were consistent with an autosomal dominant pattern, but 19 of 67 (28%) were consistent with an autosomal recessive inheritance pattern; 10 pedigrees of probable or atypical cluster headache were identified, and all were consistent with an autosomal dominant inheritance pattern. The sex ratio for cluster headache in identified pedigrees was 1.39 (103:74) in affected men and boys compared with affected women and girls, which is lower than that of the general cluster headache population.
CONCLUSIONS AND RELEVANCE
Cluster headache is an inherited disorder in a subset of families and is associated with multiple hereditary patterns. There is an unexpectedly high preponderance of women and girls with familial cluster headache; genetic subanalyses limited to female participants are necessary to further explore this observation, because these data are otherwise masked by the higher numbers of male participants with cluster headache. Overall, this systematic review supports the notion that familial cluster headache is likely the result of multiple susceptibility genes as well as environmental factors.
Topics: Cluster Headache; Female; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Male; Pedigree
PubMed: 32310255
DOI: 10.1001/jamaneurol.2020.0682 -
Scandinavian Journal of Gastroenterology Aug 2017Risk factors for small intestinal neuroendocrine tumors (SI-NETs) are not well understood. The aim of this systematic literature review was to identify risk factors for... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Risk factors for small intestinal neuroendocrine tumors (SI-NETs) are not well understood. The aim of this systematic literature review was to identify risk factors for SI-NET and to further assess these by meta-analysis.
MATERIAL AND METHODS
PubMed and abstracts from the ENETS and NANETS were searched for studies published until May 2015. Eligible studies were selected according to the PRISMA statement.
RESULTS
Seven studies evaluating six individual populations were included (study accrual period 1980-2012) in the meta-analysis, involving 765 (range 17-325) cases and 502,282 (range 52-498,376) controls. All studies were case-control by design. The following risk factors were reported in ≥2 studies: family history of any cancer, family history of colorectal cancer, ever alcohol use and ever smoking. The pooled OR was 1.34 (95% CI: 1.12-1.60; p < .01; I = 0.0%) for family history of any cancer, 1.43 (95% CI: 1.15-1.79; p < .01; I = 0.0%) for family history of colorectal cancer, 1.04 (95% CI: 0.63-1.72; p = .87; I = 65.0%) for ever alcohol use and 1.40 (95% CI: 1.06-1.86; p < .05; I = 49.3%) for ever smoking.
CONCLUSIONS
Family history of any cancer, family history of colorectal cancer and history of ever smoking were associated with an increased risk of SI-NET by meta-analysis. Alcohol consumption was not a significant risk factor for SI-NET. However, the studies reporting smoking and alcohol had a high degree of heterogeneity. Therefore, further studies are needed for clarification of smoking and alcohol as risk factors for the occurrence of SI-NET.
Topics: Alcohol Drinking; Family Health; Humans; Intestinal Neoplasms; Medical History Taking; Neuroendocrine Tumors; Pedigree; Risk Assessment; Risk Factors; Smoking
PubMed: 28394712
DOI: 10.1080/00365521.2017.1310290 -
Primary Care Diabetes Aug 2017The relatives and partners of people with type 2 diabetes are at increased risk of developing type 2 diabetes. This systematic review examines randomized controlled... (Review)
Review
The relatives and partners of people with type 2 diabetes are at increased risk of developing type 2 diabetes. This systematic review examines randomized controlled trials, written in English that tested an intervention, which aimed to modify behaviors known to delay or prevent type 2 diabetes, among the relatives or partners of people with type 2 diabetes. Study quality was assessed using the Cochrane Collaboration's tool for assessing risk of bias. Seven studies met the inclusion criteria. The majority of studies were at low risk of bias. Six studies tested an intervention in first-degree relatives of people with type 2 diabetes and one in partners. Intervention components and intervention intensity across studies varied, with those targeting diet and physical activity reporting the most significant changes in primary outcomes. Only one study did not observe significant changes in primary outcomes. There were three main recruitment approaches: advertising in the community, recruiting people through their relatives with diabetes, or identifying people as high risk by screening of their own health care contacts. Some evidence was found for potentially successful interventions to prevent type 2 diabetes among the relatives and partners of people with type 2 diabetes, although finding simple and effective methods to identify and recruit them remains a challenge. Future studies should explore the effect of patients' perceptions on their family members' behavior and capitalize on family relationships in order to increase intervention effectiveness.
Topics: Adult; Diabetes Mellitus, Type 2; Diet, Healthy; Exercise; Family; Female; Genetic Predisposition to Disease; Heredity; Humans; Male; Middle Aged; Pedigree; Phenotype; Primary Prevention; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Risk Reduction Behavior; Spouses; Treatment Outcome
PubMed: 28511962
DOI: 10.1016/j.pcd.2017.04.003 -
Frontiers in Genetics 2023Whether human sexuality is the result of nature or nurture (or their complex interplay) represents a hot, often ideologically driven, and highly polarized debate with...
Whether human sexuality is the result of nature or nurture (or their complex interplay) represents a hot, often ideologically driven, and highly polarized debate with political and social ramifications, and with varying, conflicting findings reported in the literature. A number of heritability and behavioral genetics studies, including pedigree-based investigations, have hypothesized inheritance patterns of human sexual behaviors. On the other hand, in most twin, adoption, and nuclear family studies, it was not possible to disentangle between underlying genetic and shared environmental sources. Furthermore, these studies were not able to estimate the precise extent of genetic loading and to shed light both on the number and nature of the putative inherited factors, which remained largely unknown. Molecular genetic studies offer an unprecedented opportunity to overcome these drawbacks, by dissecting the molecular basis of human sexuality and allowing a better understanding of its biological roots if any. However, there exists no systematic review of the molecular genetics of human sexuality. Therefore, we undertook this critical systematic review and appraisal of the literature, with the ambitious aims of filling in these gaps of knowledge, especially from the methodological standpoint, and providing guidance to future studies. Sixteen studies were finally retained and overviewed in the present systematic review study. Seven studies were linkage studies, four studies utilized the candidate gene approach, and five studies were GWAS investigations. Limitations of these studies and implications for further research are discussed.
PubMed: 37693319
DOI: 10.3389/fgene.2023.1184758 -
International Journal of Chronic... 2017Intergenerational associations in chronic obstructive pulmonary disease (COPD) have been well recognized and may result from genetic, gene environment, or exposure to... (Meta-Analysis)
Meta-Analysis Review
"What are my chances of developing COPD if one of my parents has the disease?" A systematic review and meta-analysis of prevalence of co-occurrence of COPD diagnosis in parents and offspring.
INTRODUCTION
Intergenerational associations in chronic obstructive pulmonary disease (COPD) have been well recognized and may result from genetic, gene environment, or exposure to life course factors. Consequently, adult offspring of parents with COPD may be at a greater risk of developing COPD. The aim of this study was to review the prevalence of co-occurrence of COPD in adult offspring with one or both parents having COPD independent of specific genetic variations.
METHODS
In total, five databases were searched for original studies in which prevalence of COPD was reported in both offspring (children) and one or both parents. Studies were excluded if COPD was not clearly defined, COPD was linked to specific genetic variations, COPD was combined with other chronic respiratory conditions, or estimates included other first-degree relatives. Data extraction (ie, sample characteristics, prevalence of COPD, and odds ratio [OR] if reported) was completed by two independent reviewers. A meta-analysis of prevalence and OR was conducted, where possible.
RESULTS
Of the 3,382 citations, 129 full texts were reviewed to include eight studies (six case-control, one cross-sectional, and one cohort) reflecting either prevalence of COPD in offspring of parents with COPD (descendent approach, n=3), which ranged from 0% to 17.3%, or prevalence of people with COPD reporting positive parental history of COPD (antecedent approach, n=5), for which the pooled prevalence was 28.6%. Offspring of people with COPD had 1.57 times greater odds (95% confidence interval =1.29-1.93; <0.001) of having COPD compared with people not having a parental history of COPD.
CONCLUSION
The prevalence of COPD in adult offspring of people with COPD is greater than population-based estimates, and the ORs indicate a higher risk in this group. This offers clinicians a potential strategy for opportunistic screening, early identification, and intervention in this at-risk group.
Topics: Child of Impaired Parents; Genetic Predisposition to Disease; Heredity; Humans; Life Style; Lung; Odds Ratio; Pedigree; Phenotype; Prevalence; Prognosis; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Risk Factors
PubMed: 28182144
DOI: 10.2147/COPD.S123933 -
Digestive Diseases and Sciences Jun 2018Inflammatory bowel disease (IBD) is a devastating immune-mediated disease on the rise in Hispanics living in the USA. Prior observational studies comparing IBD... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inflammatory bowel disease (IBD) is a devastating immune-mediated disease on the rise in Hispanics living in the USA. Prior observational studies comparing IBD characteristics between Hispanics and non-Hispanic whites (NHW) have yielded mixed results.
AIMS
We performed a meta-analysis of observational studies examining IBD phenotype in Hispanics compared to NHW.
METHODS
We conducted a systematic search of US-based studies comparing IBD subtype (Ulcerative Colitis: UC or Crohn's disease: CD) and phenotype (disease location and behavior) between Hispanics and NHW. We evaluated differences in age at IBD diagnosis, the presence of family history and smoking history. A random effects model was chosen "a priori." Categorical and continuous variables were analyzed using odds ratio (OR) or standard mean difference (SMD), respectively.
RESULTS
Seven studies were included with 687 Hispanics and 1586 NHW. UC was more common in Hispanics compared to NHW (OR 2.07, CI 1.13-3.79, p = 0.02). Location of disease was similar between Hispanics and NHW except for the presence of upper gastrointestinal CD, which was less common in Hispanics (OR 0.58, CI 0.32-1.06, p = 0.07). Hispanics were less likely to smoke (OR 0.48, CI 0.26-0.89, p = 0.02) or have a family history of IBD (OR 0.35, CI 0.22-0.55, p < 0.001). CD behavior classified by Montreal classification and age at IBD diagnosis were similar between Hispanics and NHW.
CONCLUSION
UC was more common among US Hispanics compared to NHW. Age at IBD diagnosis is similar for both Hispanics and NHW. For CD, disease behavior is similar, but Hispanics show a trend for less upper gastrointestinal involvement. A family history of IBD and smoking history were less common in Hispanics.
Topics: Age Factors; Colitis, Ulcerative; Crohn Disease; Genetic Predisposition to Disease; Hispanic or Latino; Humans; Observational Studies as Topic; Odds Ratio; Pedigree; Phenotype; Risk Factors; Smoking; United States; White People
PubMed: 29594975
DOI: 10.1007/s10620-018-5022-7 -
The American Journal of Gastroenterology Nov 2015First-degree relatives (FDRs) of patients with celiac disease (CD) are at high risk for CD and prevalence among them varies from 1.6 to 38%. The risk of having CD among... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
First-degree relatives (FDRs) of patients with celiac disease (CD) are at high risk for CD and prevalence among them varies from 1.6 to 38%. The risk of having CD among FDRs if the FDR is sister, brother, mother, father, son, or daughter of index patient with CD is not known. We conducted a meta-analysis and calculated pooled prevalence of CD among FDRs, second-degree relatives (SDRs), and specific relations with index patient.
METHODS
On search of literature, 2,259 articles appeared of which 54 articles were included in this meta-analysis. Diagnosis of CD was based on standard criteria.
RESULTS
Pooled prevalence of CD was 7.5% (95% confidence interval (CI) 6.3%, 8.8%) in 10,252 FDRs and 2.3% (95% CI 1.3%, 3.8%) in 642 SDRs. Pooled prevalence of CD was highest in siblings (8.9%), followed by offsprings (7.9%) and parents (3.0%). Female FDRs had higher prevalence than male FDRs (8.4% vs. 5.2%, P=0.047). While sisters and daughters of index patient had the highest risk of having CD (1 in 7 and 1 in 8, respectively), the risk was 1 in 13 in sons, 1 in 16 in brothers, 1 in 32 in mothers, and 1 in 33 in fathers. There were also differences in the pooled prevalence of CD in FDRs according to their geographic location.
CONCLUSIONS
Pooled prevalence of CD among FDRs is 7.5% and varies considerably with their relationship with the index patient. The risk of CD in FDRs also varies according to gender and geographical location.
Topics: Asia; Celiac Disease; Europe; Fathers; Female; Humans; Male; Mothers; North America; Pedigree; Prevalence; Risk Factors; Sex Factors; Siblings; South America
PubMed: 26416192
DOI: 10.1038/ajg.2015.296 -
The Journal of Steroid Biochemistry and... Nov 201717β-Hydroxysteroid dehydrogenase 3 deficiency is a rare autosomal recessive cause of 46, XY disorders of sex development resulting from HSD17B3 gene mutations, however,... (Review)
Review
17β-Hydroxysteroid dehydrogenase 3 deficiency is a rare autosomal recessive cause of 46, XY disorders of sex development resulting from HSD17B3 gene mutations, however, no case has been reported in East Asia. The aim of this study was to report three Chinese 46, XY females with 17β-HSD3 deficiency in a single center and perform a systematic review of the literature. Clinical examination, endocrine evaluation and HSD17B3 gene sequencing were performed in the three Chinese phenotypically females (two sisters and one unrelated patient). Relevant articles were searched by using the term "HSD17B3" OR "17beta-HSD3 gene" with restrictions on language (English) and species (human) in Pubmed and Embase. All the three phenotypically female subjects showed 46, XY karyotype, inguinal masses, decreased testosterone and increased androstenedione. Two novel homozygous mutations (W284X and c.124_127delTCTT) in HSD17B3 gene were identified. A systematic review found a total of 121 pedigrees/158 patients, with 78.5% (124/158) of patients assigned as females, 15.2% (24/158) from females to males, and 5.1% (8/158) raised as males. The most common mutation was c.277+4C>T (allele frequency: 25/72) for patients from Europe, and R80Q (allele frequency: 21/54) for patients from West Asia. The testicular histology showed normal infantile testicular tissue in 100% (9/9) infantile patients, normal quantity germ cells in 44.4% (8/18) prepubertal patients and 19.0% (4/21) pubertal and adult patients. We reported the first East Asian 17β-hydroxysteroid dehydrogenase 3 deficiency cases. Additional literature reviews found founder effects among patients with different ethnic background and early orchiopexy may benefit fertility in patients assigned as males. These findings may significantly expand the clinical, ethnic and genetic spectrum of 17β-hydroxysteroid dehydrogenase 3 deficiency.
Topics: 17-Hydroxysteroid Dehydrogenases; Adolescent; Asian People; Child; Disorder of Sex Development, 46,XY; Female; Humans; Mutation
PubMed: 28847746
DOI: 10.1016/j.jsbmb.2017.08.012 -
Journal of Clinical Oncology : Official... Jan 2019An ASCO provisional clinical opinion (PCO) offers timely clinical direction to ASCO's membership and other health care providers. This PCO addresses identification and...
PURPOSE
An ASCO provisional clinical opinion (PCO) offers timely clinical direction to ASCO's membership and other health care providers. This PCO addresses identification and management of patients and family members with possible predisposition to pancreatic adenocarcinoma.
METHODS
ASCO convened an Expert Panel and conducted a systematic review of the literature published from January 1998 to June 2018. Results of the databases searched were supplemented with hand searching of the bibliographies of systematic reviews and selected seminal articles and contributions from Expert Panel members' curated files.
PROVISIONAL CLINICAL OPINION
All patients diagnosed with pancreatic adenocarcinoma should undergo assessment of risk for hereditary syndromes known to be associated with an increased risk for pancreatic adenocarcinoma. Assessment of risk should include a comprehensive review of family history of cancer. Individuals with a family history of pancreatic cancer affecting two first-degree relatives meet criteria for familial pancreatic cancer (FPC). Individuals (cancer affected or unaffected) with a family history of pancreatic cancer meeting criteria for FPC, those with three or more diagnoses of pancreatic cancer in same side of the family, and individuals meeting criteria for other genetic syndromes associated with increased risk for pancreatic cancer have an increased risk for pancreatic cancer and are candidates for genetic testing. Germline genetic testing for cancer susceptibility may be discussed with individuals diagnosed with pancreatic cancer, even if family history is unremarkable. Benefits and limitations of pancreatic cancer screening should be discussed with individuals whose family history meets criteria for FPC and/or genetic susceptibility to pancreatic cancer. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .
Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Genetic Counseling; Genetic Predisposition to Disease; Genetic Testing; Heredity; Humans; Pancreatic Neoplasms; Pedigree; Phenotype; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors
PubMed: 30457921
DOI: 10.1200/JCO.18.01489