Validity of a personal and family history of cataract and cataract surgery in genetic studies.

PURPOSE:

To determine the accuracy of a history of cataract and cataract surgery (self-report and for a sibling), and to determine which demographic, cognitive, and medical factors are predictive of an accurate history.

METHODS:

All participants in the Salisbury Eye Evaluation (SEE) project and their locally resident siblings were questioned about a personal and family history of cataract or cataract surgery. Lens grading at the slit lamp, using standardized photographs and a grading system, was performed for both SEE participants (probands) and their siblings. Cognitive testing and a history of systemic comorbidities were also obtained for all probands.

RESULTS:

Sensitivity of a history of cataract provided on behalf of a sibling was 32%, specificity 98%. The performance was better for a history of cataract surgery: sensitivity 90%, specificity 89%. For self-report of cataract, sensitivity was also low at 55%, with specificity at 77%. Self-report of cataract surgery gave a much better performance: sensitivity 94%, specificity 100%. Different cutoffs in the definition of cataract had little impact. Factors predicting a correct history of cataract included high school or greater education in the proband (odds ratio [OR] = 1.13, 95% confidence interval [CI]1.02-1.25) and younger sibling (but not proband) age (OR = 0.94 for each year of age, 95% CI 0.90-0.99). Gender, race and Mini-Mental Status Examination (MMSE) result were not predictive.

CONCLUSIONS:

Whereas accurate self and family histories for cataract surgery may be obtainable, it is difficult to ascertain cataract status accurately from history alone.

Parent-child agreement and prevalence estimates of diagnoses in childhood: direct interview versus family history method.

Diagnostic information on children is typically elicited from both children and their parents. The aims of the present paper were to: (1) compare prevalence estimates according to maternal reports, paternal reports and direct interviews of children [major depressive disorder (MDD), anxiety and attention-deficit and disruptive behavioural disorders]; (2) assess mother-child, father-child and inter-parental agreement for these disorders; (3) determine the association between several child, parent and familial characteristics and the degree of diagnostic agreement or the likelihood of parental reporting; (4) determine the predictive validity of diagnostic information provided by parents and children. Analyses were based on 235 mother-offspring, 189 father-offspring and 128 mother-father pairs. Diagnostic assessment included the Kiddie-schedule for Affective Disorders and Schizophrenia (K-SADS) (offspring) and the Diagnostic Interview for Genetic Studies (DIGS) (parents and offspring at follow-up) interviews. Parental reports were collected using the Family History - Research Diagnostic Criteria (FH-RDC). Analyses revealed: (1) prevalence estimates for internalizing disorders were generally lower according to parental information than according to the K-SADS; (2) mother-child and father-child agreement was poor and within similar ranges; (3) parents with a history of MDD or attention deficit hyperactivity disorder (ADHD) reported these disorders in their children more frequently; (4) in a sub-sample followed-up into adulthood, diagnoses of MDD, separation anxiety and conduct disorder at baseline concurred with the corresponding lifetime diagnosis at age 19 according to the child rather than according to the parents. In conclusion, our findings support large discrepancies of diagnostic information provided by parents and children with generally lower reporting of internalizing disorders by parents, and differential reporting of depression and ADHD by parental disease status. Follow-up data also supports the validity of information provided by adolescent offspring.

Family history of cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

Alcohol and tobacco consumption are well-recognized risk factors for head and neck cancer (HNC). Evidence suggests that genetic predisposition may also play a role. Only a few epidemiologic studies, however, have considered the relation between HNC risk and family history of HNC and other cancers. We pooled individual-level data across 12 case-control studies including 8,967 HNC cases and 13,627 controls. We obtained pooled odds ratios (OR) using fixed and random effect models and adjusting for potential confounding factors. All statistical tests were two-sided. A family history of HNC in first-degree relatives increased the risk of HNC (OR=1.7, 95% confidence interval, CI, 1.2-2.3). The risk was higher when the affected relative was a sibling (OR=2.2, 95% CI 1.6-3.1) rather than a parent (OR=1.5, 95% CI 1.1-1.8) and for more distal HNC anatomic sites (hypopharynx and larynx). The risk was also higher, or limited to, in subjects exposed to tobacco. The OR rose to 7.2 (95% CI 5.5-9.5) among subjects with family history, who were alcohol and tobacco users. A weak but significant association (OR=1.1, 95% CI 1.0-1.2) emerged for family history of other tobacco-related neoplasms, particularly with laryngeal cancer (OR=1.3, 95% CI 1.1-1.5). No association was observed for family history of nontobacco-related neoplasms and the risk of HNC (OR=1.0, 95% CI 0.9-1.1). Familial factors play a role in the etiology of HNC. In both subjects with and without family history of HNC, avoidance of tobacco and alcohol exposure may be the best way to avoid HNC.

Analytical relationship between family history and genetic and environmental risks, with application to female breast cancer

It is well established in genetic epidemiology that family history is an important indicator of familial aggregation of disease in a family. A strong genetic risk factor or an environmental risk factor with high familial correlation can result in a strong family history. In this paper, family history refers to the number of first-degree relatives affected with the disease. Cui and Hopper (Journal of Epidemiology and Biostatistics 2001; 6: 331-342) proposed an analytical relationship between family history and relevant genetic parameters. In this paper we expand the relationship to both genetic and environmental risk factors. We established a closed-form formula for family history as a function of genetic and environmental parameters which include genetic and environmental relative risks, genotype frequency, prevalence and familial correlation of the environmental risk factor. The relationship is illustrated by an example of female breast cancer in Australia. For genetic and environmental relative risks less than 10, most of the female breast cancer cases occur between the age of 40 and 60 years. A higher genetic or environmental relative risk will move the peak of the distribution to a younger age. A more common disease allele or more prevalent environmental risk factor will move the peak to an older age. For a proband with breast cancer, it is most likely (with probability ge80%) that none of her first-degree relatives is affected with the disease. To enable the probability of having a positive family history to reach 50%, the environmental relative risks must be extremely as high as 100, the familial correlation as high as 0.8 and the prevalence as low as 0.1. For genetic risk alone, even the relative risk is as high as 100, the probability of having a positive family history can only reach about 30%. This suggests that the environmental risk factor seems to play a more important role in determining a strong family history than the genetic risk factor.

Risk of prostate cancer associated with a family history in an era of rapid increase in prostate cancer diagnosis (Australia)

OBJECTIVE: We conducted a case-control study of prostate cancer and familial risk of the disease in Australia between 1994 and 1998, a period during which the incidence of prostate cancer increased dramatically with widespread use of prostate-specific antigen (PSA) testing. METHODS: 1475 cases and 1405 controls were asked about prostate cancer in their first-degree relatives. Odds ratios (OR) were calculated using logistic regression. RESULTS: Cases were more likely to report a family history of prostate cancer than controls (OR 3.0; 95% confidence interval (CI) 2.3-3.9) and cases reporting an affected relative were younger (58.8 versus 60.9 years, p < 0.0001). The OR for an affected first-degree relative increased with increasing number of affected relatives and decreased with increasing age of the case. The OR for more than one affected first-degree relative was 6.9 (95% CI 2.7-18). The OR for an affected brother was 3.9 (95% CI 2.5-6.1) and for an affected father was 2.9 (95% CI 2.1-3.9) but these were not significantly different (p = 0.2). When analyses were repeated including only diagnoses made in relatives prior to 1992, the risks were generally similar except that the OR for an affected brother decreased to 3.1 (95% CI 1.2-3.9). When only relatives' diagnoses made after 1991 were included results were again similar to those for all relatives, although the effect for brothers was greater and the attenuation with age at diagnosis dissipated. CONCLUSIONS: The recent introduction of PSA testing that has resulted in a greater prevalence of apparent prostate cancer, does not appear to have substantially altered familial risks of disease, although effects associated with brothers may be inflated.

Risk perception, risk communication and message framing : breast cancer and family history

Examines the relationships between risk perception, risk communication, and health protective behaviour in relation to breast cancer and family history. Qualitative research was conducted to develop a printed community resource. Theoretical and practical implications for health behaviour theory and risk communication are identified.

Family history and the Great War in Australia

The boom in family history that is a hallmark of so much historical activity around the globe over the last three decades is one contributor to the resurgence of interest in the Great War itself. In Australia, as elsewhere in the western world, family history and the resources dedicated to it have been expanding rapidly. This chapter investigates recent practices of family history of the Great War in Australia. Our aim is to examine the role of family history in producing and reproducing knowledge of the Great War within Australian families, and the relationship between the conduct and transmission of family history on the one hand, and the contours of cultural memory on the other.

Investigation of single-strand conformational polymorphism of the TP53 gene in women with a family history of breast cancer

Breast cancer in families with germ line mutations in the TP53 gene has been described in the medical literature. Mutation screening for susceptibility genes should allow effective prophylactic and preventive measures. Using single-strand conformational polymorphism, we screened for mutations in exons 5, 6, 7 and 8 of gene TP53 in the peripheral blood of 8 young non-affected members (17 to 36 years old) of families with a history of breast cancer. Studies of this type on young patients (mean age, 25 years) are very rare in the literature. The identification of these mutations would contribute to genetic counseling of members of families with predisposition to breast cancer. The results obtained did not show any polymorphism indicating mutation. In our sample, the familial tumorigenesis is probably related to other gene etiologies.

Genomic alterations in patients showing multiple primary tumors and family history of cancer

Multiple primary tumors (MPT) are a major cause of mortality and morbidity among patients that have survived after the treatment of a first cancer. It has been proposed that after the first primary tumor, high risk of a subsequent tumor could be associated with radiotherapy used as treatment for the first cancer. Other potential risk factors include unhealthy lifestyle, genetic predisposition, aging, environmental determinants or an interaction between these factors. However, an association between the presence of MPT and family history of cancer in cases without clinical and molecular evidence of a known hereditary cancer syndrome is rarely described. Genomic DNA from 12 patients with at least two primary tumors and without mutations on TP53 was evaluated by CytoScan HD Array (Affymetrix). Chromosome Analysis Suite (ChAS) software v.2.0.1 was used considering at least 50 markers for gains; 25 for losses and a minimum of 5Mb for cnLOHs. Data from 1038 phenotypically healthy individuals (Affymetrix) and from Database of Genomic Variants were used as reference. Only alterations found in <1% (rare) or never described (new rare) in the reference population were considered. All cases, except one, presented a family history of cancer. Five cases developed MTP after radiotherapy and only one was located in the same treated area. It was detected 67 rare and 15 new rare genomic alterations encompassing 5.906 genes: 17 losses, 29 gains, and 36 cnLOH. X chromosome presented the higher number of alterations. Two patients with breast cancer presented a large deletion/cnLOH on 7q21. Enrichment analysis revealed 1275 genes associated with breast cancer (p= 0.001), which was diagnosed in 6 patients and their family members (all negative for BRCA1/2 or TP53 mutations). cnLOHs accounted for 44% of all the alterations. A significant proportion of cases (11/12) presented family history of cancer and the patients were not submitted to radiotherapy (7/12). We demonstrated the presence of rare genomic alterations in patients with MPT suggesting their involvement in the MPT development. cnLOH may arise as a new mechanism associated with the risk to develop MPT. All authors have declared no conflicts of interest.

Whitener Family History - Accession 706 - M108 (138)

The Whitener Family History consists of a history written by Robert Campbell Whitener, Sr. in 1987 titled "Gold Mining Son of a Gold Miner" David William Whitener: His Ancestors and Descendants 1717-1987.

A family history of serious complications due to BCG vaccination is a tool for the early diagnosis of severe primary immunodeficiency

Severe Combined Immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency (PID). Complications of BCG vaccination, especially disseminated infection and its most severe forms, are known to occur in immunodeficient patients, particularly in SCID. A carefully taken family history before BCG injection as well as delaying vaccination if PID is suspected could be a simple and effective method to avoid inappropriate vaccination of an immunodeficient child in some cases until the prospect of newborn screening for SCID has been fully developed. We describe a patient with a very early diagnosis of SCID, which was suspected on the basis of the previous death of two siblings younger than one year due to severe complications secondary to the BCG vaccine. We suggest that a family history of severe or fatal reactions to BCG should be included as a warning sign for an early diagnosis of SCID.

Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes

BACKGROUND: Both nutritional and genetic factors are involved in the pathogenesis of nonalcoholic fatty liver disease and insulin resistance. OBJECTIVE: The aim was to assess the effects of fructose, a potent stimulator of hepatic de novo lipogenesis, on intrahepatocellular lipids (IHCLs) and insulin sensitivity in healthy offspring of patients with type 2 diabetes (OffT2D)--a subgroup of individuals prone to metabolic disorders. DESIGN: Sixteen male OffT2D and 8 control subjects were studied in a crossover design after either a 7-d isocaloric diet or a hypercaloric high-fructose diet (3.5 g x kg FFM(-1) x d(-1), +35% energy intake). Hepatic and whole-body insulin sensitivity were assessed with a 2-step hyperinsulinemic euglycemic clamp (0.3 and 1.0 mU x kg(-1) x min(-1)), together with 6,6-[2H2]glucose. IHCLs and intramyocellular lipids (IMCLs) were measured by 1H-magnetic resonance spectroscopy. RESULTS: The OffT2D group had significantly (P < 0.05) higher IHCLs (+94%), total triacylglycerols (+35%), and lower whole-body insulin sensitivity (-27%) than did the control group. The high-fructose diet significantly increased IHCLs (control: +76%; OffT2D: +79%), IMCLs (control: +47%; OffT2D: +24%), VLDL-triacylglycerols (control: +51%; OffT2D: +110%), and fasting hepatic glucose output (control: +4%; OffT2D: +5%). Furthermore, the effects of fructose on VLDL-triacylglycerols were higher in the OffT2D group (group x diet interaction: P < 0.05). CONCLUSIONS: A 7-d high-fructose diet increased ectopic lipid deposition in liver and muscle and fasting VLDL-triacylglycerols and decreased hepatic insulin sensitivity. Fructose-induced alterations in VLDL-triacylglycerols appeared to be of greater magnitude in the OffT2D group, which suggests that these individuals may be more prone to developing dyslipidemia when challenged by high fructose intakes. This trial was registered at clinicaltrials.gov as NCT00523562.