The role of hereditary nonpolyposis colorectal cancer in the management of familial ovarian cancer.

PURPOSE: Familial ovarian cancer is most often associated with hereditary breast and ovarian cancer, implicating mutations in the BRCA1 and BRCA2 genes. Hereditary nonpolyposis colorectal cancer, another common syndrome, is also associated with ovarian cancer and is caused by DNA mismatch repair genes. We sought to identify the role of hereditary nonpolyposis colorectal cancer in women with family histories of ovarian cancer. METHODS: The likelihood of a genetic syndrome in 226 oophorectomized women in the Gilda Radner Familial Ovarian Cancer Registry was determined by pedigree analysis using clinical criteria and by calculating the probability of a mutation in genes responsible for hereditary breast and ovarian cancer and hereditary nonpolyposis colorectal cancer using available risk models. RESULTS: Some 86% had a BRCA gene mutation likelihood of 7.8% or higher, warranting consideration of hereditary breast and ovarian cancer. Of the 32 women below this threshold, 4 (12.5%) had family histories that met criteria for clinical diagnosis of hereditary nonpolyposis colorectal cancer. In addition, 16 women (7%) with a BRCA mutation likelihood greater than 7.8% met clinical criteria for hereditary nonpolyposis colorectal cancer or warranted its inclusion in the differential diagnosis. Among all study respondents, 9% had family histories warranting consideration of hereditary nonpolyposis colorectal cancer. CONCLUSION: Hereditary nonpolyposis colorectal cancer should be considered in the differential diagnosis of women with family histories of ovarian cancer.     

Mouse models of human familial cancer syndromes

As many as 5% of human cancers appear to be of hereditable etiology. Of the more than 50 characterized familial cancer syndromes, most involve disease affecting multiple organs and many can be traced to one or more abnormalities in specific genes. Studying these syndromes in humans is a difficult task, especially when it comes to genes that may manifest themselves early in gestation. It has been made somewhat easier with the development of genetically engineered mice (GEM) that phenotypically mimic many of these inheritable human cancers. The past 15 years has seen the establishment of mouse lines heterozygous or homozygous null for genes known or suspected of being involved in human cancer syndromes, including APC, ATM, BLM, BRCA1, BRCA2, LKB1, MEN1, MLH, MSH, NF1, TP53, PTEN, RB1, TSC1, TSC2, VHL, and XPA. These lines not only provide models for clinical disease and pathology, but also provide avenues to investigate molecular pathology, gene-gene and protein-tissue interaction, and, ultimately, therapeutic intervention. Possibly of even greater importance, they provide a means of looking at placental and fetal tissues, where genetic abnormalities are often first detected and where they may be most easily corrected. We will review these mouse models, examine their usefulness in medical research, and furnish sources of animals and references.     

The prevalence of allergic skin test reactivity to eight common aeroallergens in the U.S. population: results from the second National Health and Nutrition Examination Survey

Immediate hypersensitivity skin tests to eight select allergens were performed on a sample (N = 16,204) of the civilian noninstitutional population of the United States, 6 to 74 years of age, in the second National Health and Nutrition Examination Survey (NHANES II). The eight allergens were house dust, cat, dog, Alternaria, mixed giant/short ragweed, oak, perennial ryegrass, and Bermuda grass. Skin test reactivity was defined as a mean erythema diameter greater than or equal to 10.5 mm at the 20-minute reading. Overall, 20.2% of the participants reacted to at least one allergen. Peak reactivity occurred in the 12 to 24-year-old age group. Reactivity was higher in blacks versus whites, but the difference did not reach statistical significance (23.2% versus 19.8%; p greater than 0.05). Male participants had an increased prevalence of reactivity versus female participants in whites (22.0% versus 17.6%), but not in blacks (23.2% versus 23.3%). Skin test reactivity increased in both whites and blacks with increasing income and education. The prevalence of skin test reactivity was higher in urban versus rural areas, but the difference was statistically significant only for whites (whites, 21.6% versus 16.4%; blacks, 23.8% versus 18.4%; p greater than 0.05). With logistic regression, the most important predictors of skin test reactivity in whites were age, sex, urban residence, and poverty status. In blacks, the most important predictors were age, urban residence, and poverty status.     

The prevalence of delayed and advanced sleep phase syndromes

To determine the prevalence of the delayed sleep phase syndrome (DSPS) and the contrasting advanced sleep phase syndrome (ASPS), a cross-sectional nationwide epidemiological study was performed in Norway. Screening questionnaires were sent to a random sample of 10,000 adult individuals (18-67 y), of both sexes, taken from the National register of Norway. The response rate was 77%. Diagnoses of DSPS and ASPS were based on International Classification of Sleep Disorders (ICSD) criteria. All individuals suspected of having DSPS or ASPS were requested to fill out a second questionnaire, and a sleep log for four weeks. Subjects for whom the suspicion of DSPS or ASPS could be upheld were contacted by telephone for a final confirmation. Of the 129 possible DSPS cases identified from the screening questionnaires, 17 (9 f; 8 m) remained with the confirmed diagnosis of DSPS. The prevalence was calculated to be 0.17% (95% Confidence Intervals: 0.10-0.28). Thirteen individuals had a mild to moderate DSPS and four had a severe DSPS. The mean age of onset was 15.4 y, and mean duration was 19.2 y. There was no significant correlation between prevalence and age. A sleep phase delay (MSPD) induced by social/environmental or psychological factors was found in 55 subjects (prevalence = 0.72%). Using strict ICSD criteria, no case of ASPS was detected, confirming earlier assumptions of the extreme rarity of this condition.     

Gene discovery in familial cancer syndromes by exome sequencing: prospects for the elucidation of familial colorectal cancer type X

Recent advances in genotyping and sequencing technologies have provided powerful tools with which to explore the genetic basis of both Mendelian (monogenic) and sporadic (polygenic) diseases. Several hundred genome-wide association studies have so far been performed to explore the genetics of various polygenic or complex diseases including those cancers with a genetic predisposition. Exome sequencing has also proven very successful in elucidating the etiology of a range of hitherto poorly understood Mendelian disorders caused by high-penetrance mutations. Despite such progress, the genetic etiology of several familial cancers, such as familial colorectal cancer type X, has remained elusive. Familial colorectal cancer type X and Lynch syndrome are similar in terms of their fulfilling certain clinical criteria, but the former group is not characterized by germline mutations in DNA mismatch-repair genes. On the other hand, the genetics of sporadic colorectal cancer have been investigated by genome-wide association studies, leading to the identification of multiple new susceptibility loci. In addition, there is increasing evidence to suggest that familial and sporadic cancers exhibit similarities in terms of their genetic etiologies. In this review, we have summarized our current knowledge of familial colorectal cancer type X, discussed current approaches to probing its genetic etiology through the application of new sequencing technologies and the recruitment of the results of colorectal cancer genome-wide association studies, and explore the challenges that remain to be overcome given the uncertainty of the current genetic model (ie, monogenic vs polygenic) of familial colorectal cancer type X.     

The Prevalence of Short Sleep Duration by Industry and Occupation in the National Health Interview Survey

Study Objectives:

To explore whether employment in industries likely to have non-standard work schedules (e.g., manufacturing and service) and occupations with long work-weeks (e.g., managerial/ professional, sales, and transportation) is associated with an increased risk of short sleep duration.

Design:

Cross-sectional epidemiologic survey.

Setting:

Household-based face-to-face survey of civilian, non-institutionalized US residents.

Participants:

Sample adults interviewed for the National Health Interview Survey in 1985 or 1990 (N = 74,734) or between 2004 and 2007 (N = 110,422). Most analyses focused on civilian employed workers interviewed between 2004 and 2007 (N = 66,099).

Interventions:

N/A

Measurements and Results:

The weighted prevalence of self-reported short sleep duration, defined as ≤6 h per day, among civilian employed workers from 2004-2007 was 29.9%. Among industry categories, the prevalence of short sleep duration was greatest for management of companies and enterprises (40.5%), followed by transportation/warehousing (37.1%) and manufacturing (34.8%). Occupational categories with the highest prevalence included production occupations in the transportation/warehousing industry, and installation, maintenance, and repair occupations in both the transportation/warehousing industry and the manufacturing industry. In the combined sample from 1985 and 1990, 24.2% of workers reported short sleep duration; the prevalence of short sleep duration was significantly lower during this earlier time period compared to 2004–2007 for 7 of 8 industrial sectors.

Conclusions:

Self-reported short sleep duration among US workers varies by industry and occupation, and has increased over the past two decades. These findings suggest the need for further exploration of the relationship between work and sleep, and development of targeted interventions for specific industry/occupation groups.

Citation:

Luckhaupt SE; Tak S; Calvert GM. The prevalence of short sleep duration by industry and occupation in the National Health Interview Survey. SLEEP 2010;33(2):149-159     

Molecular pathology of familial gastric cancer, with an emphasis on hereditary diffuse gastric cancer

Gastric cancer is one of the major causes of cancer-related death worldwide. Familial clustering is observed in about 10% of cases; 1-3% of cases are hereditary. In the latter group, a syndrome which has been well characterised is hereditary diffuse gastric cancer; this is specifically associated with CDH1 (E-cadherin) germline mutations in about 30% of families. In this article, the state of the art of familial gastric cancer regarding the clinical, molecular and pathology features is reviewed, as well as the practical aspects for a correct diagnosis and clinical management.     

The role of internalizing and externalizing liability factors in accounting for gender differences in the prevalence of common psychopathological syndromes

BACKGROUND: We hypothesized that gender differences in average levels on the internalizing and externalizing factors that account for co-morbidity among common psychopathological syndromes in both men and women account for gender differences in the prevalence of specific syndromes. METHOD: The latent structure of 11 syndromes was examined in a middle-aged (mean age=52.66 years, s.d.=5.82) sample of 2992 (37% men) members of the community-based Minnesota Twin Registry (MTR) assessed using 10 scales of the Psychiatric Diagnostic Screening Questionnaire (PDSQ) and an adult antisocial behavior scale. Confirmatory factorial invariance models were applied to a best-fitting, internalizing-externalizing model. RESULTS: A 'strong gender invariance model' fit best, indicating that gender differences in the means of individual syndromes were well accounted for by gender differences in mean levels of internalizing and externalizing. Women exhibited higher mean levels of internalizing (d=0.23) and lower mean levels of externalizing (d=-0.52) than men. CONCLUSIONS: These findings suggest that risk factors for common mental disorders exhibiting gender differences may influence prevalence at the latent factor level. Future research may benefit from focusing on both the latent factor and individual syndrome levels in explaining gender differences in psychopathology.     

The kaleidoscope of autoimmunity: multiple autoimmune syndromes and familial autoimmunity

Three related lines of evidence sustain the common origin for autoimmune diseases (ADs). First, the clinical evidence corresponding to the kaleidoscope of autoimmunity, which is the co-occurrence of various ADs within an individual or co-occurrence within members of a nuclear family. Second, the physiopathologic evidence indicating that the pathologic mechanisms might be similar among ADs. Last, the genetic evidence indicating that autoimmune phenotypes could represent pleiotropic outcomes of nonspecific disease genes. The two conditions that better illustrate the kaleidoscope of autoimmunity are multiple autoimmune syndromes and familial autoimmunity. The multiple autoimmune syndromes consist of the presence of three or more well-defined autoimmune conditions in a single patient. The familial autoimmunity is defined as the presence of diverse ADs on multiple members of a nuclear family. Herein, both the multiple autoimmune syndromes and familial autoimmunity are discussed and various epidemiological factors considered in the context of the common genetic background of autoimmunity.     

Sleep Duration and Cardiovascular Disease: Results from the National Health Interview Survey

Background:

Previous studies have shown that both short and long sleep durations are related to increased likelihood of diabetes and hypertension. However, the relation between sleep duration and cardiovascular disease (CVD) is not clear. We examined the hypothesis that compared with sleep duration of 7 hours, shorter and longer sleep durations are independently related to CVD.

Methods:

We conducted a cross-sectional study of 30,397 National Health Interview Survey 2005 participants ≥ 18 years of age (57.1% women). Sleep duration was categorized as ≤ 5 hours, 6 hours, 7 hours, 8 hours, and ≥ 9 hours. The main outcome of interest was the presence of any CVD (n = 2146), including myocardial infarction, angina, and stroke.

Results:

We found both short and long sleep durations to be independently associated with CVD, independent of age, sex, race-ethnicity, smoking, alcohol intake, body mass index, physical activity, diabetes mellitus, hypertension, and depression. Compared with a sleep duration of 7 h (referent), the multivariate odds ratio (95% confidence interval) of CVD was 2.20 (1.78, 2.71), 1.33 (1.13, 1.57), 1.23 (1.06, 1.41), and 1.57 (1.31, 1.89) for sleep duration ≤ 5 h, 6 h, 8 h, and ≥ 9 h. This association persisted in subgroup analyses by gender, race-ethnicity, and body mass index categories. Also, similar associations were observed when we examined myocardial infarction and stroke separately.

Conclusion:

Compared with sleep duration of 7 h, there was a positive association between both shorter and longer sleep durations and CVD in a representative sample of US adults. These results suggest that sleep duration may be an important marker of CVD.

Citation:

Sabanayagam C; Shankar A. Sleep duration and cardiovascular disease: results from the National Health Interview Survey. SLEEP 2010;33(8):1037-1042.     

Probable common origin of a hereditary fundus dystrophy (Sorsby''s familial pseudoinflammatory macular dystrophy) in an English and Australian family.

A genealogical link was established six generations back between a family living in England and Australia, and one of the families reported originally by Sorsby et al (1949) as suffering from autosomal dominant inflammatory macular dystrophy (fundus dystrophy). The onset--in the fifth decade of life--and the progress of the condition, which usually ends in blindness, has been observed in a number of patients and the prodromal development of a colour vision deficiency in some of them confirmed. This defect is fundamentally different from the X-linked colour vision defects and merits further investigation.     

Insomnia associated with valerian and melatonin usage in the 2002 National Health Interview Survey

STUDY OBJECTIVE: Many people use dietary supplements or herbal products to help them sleep. We analyzed the associations between melatonin use and insomnia and between valerian use and insomnia in a representative sample of the United States population. DESIGN AND PARTICIPANTS: The data reported upon here were collected in the 2002 Alternative Health/Complementary and Alternative Medicine (CAM) Supplement to the National Health Interview Survey. This was a survey of 31,044 personal interviews that constituted an age-representative and socioeconomically representative sample of the civilian noninstitutionalized population of the United States. RESULTS: Of the survey sample, 5.9% used valerian and 5.2% used melatonin. Of those using valerian, 29.9% endorsed insomnia as 1 reason for CAM use, and, of melatonin users, 27.5% endorsed insomnia as 1 reason for CAM use. Relatively greater use occurred in individuals under age 60 years. The decision to use such substances was made in consultation with a health care provider less than half of the time. CONCLUSIONS: Large segments of the United States population used valerian or melatonin for insomnia within the year preceding the survey, and usage typically fell outside the purview of the health care system.     

The genetics of hereditary colon cancer

The genetic basis of sporadic colorectal cancer has illuminated our knowledge of human cancer genetics. This has been facilitated and catalyzed by an appreciation and deep understanding of the forms of colorectal cancer that harbor an inherited predisposition, including familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome, the hamartomatous polyposis syndromes, and certain other rare syndromes. Identification of germline mutations in pivotal genes underlying the inherited forms of colorectal cancer has yielded many dividends, including functional dissection of critical molecular pathways that have been revealed to be important in development, cellular homeostasis, and cancer; new approaches in chemoprevention, molecular diagnostics and genetic testing, and therapy; and underscoring genotypic-phenotypic relationships.