Health-related predictors of cancer registry-notified cancer of unknown primary site (CUP).

BACKGROUND: The relationship between comorbid disease and health service use and risk of cancer of unknown primary site (CUP) is uncertain. METHODS: A prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia. Baseline questionnaire data were linked to cancer registration, health service records 4-27 months prior to diagnosis, and mortality data. We compared individuals with incident registry-notified CUP (n = 327; 90% C80) to two sets of randomly selected controls (3:1): (i) incident metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In fully adjusted models incorporating sociodemographic and lifestyle factors, people with cancer registry-notified CUP were more likely to have fair compared with excellent self-rated overall health (OR 1.78, 95% CI 1.01-3.14) and less likely to self-report anxiety (OR 0.48, 95% CI 0.24-0.97) than those registered with metastatic cancer of known primary. Compared to general cohort population controls, people registered with CUP were more likely to have poor rather than excellent self-rated overall health (OR 6.22, 95% CI 1.35-28.6), less likely to self-report anxiety (OR 0.28, 95% CI 0.12-0.63), and more likely to have a history of diabetes (OR 1.89, 95% CI 1.15-3.10) or cancer (OR 1.62, 95% CI 1.03-2.57). Neither tertiary nor community-based health service use independently predicted CUP risk. CONCLUSION: Low self-rated health may be a flag for undiagnosed cancer, and an investigation of its clinical utility in primary care appears warranted.

Demographic, social and lifestyle risk factors for cancer registry-notified cancer of unknown primary site (CUP).

BACKGROUND: Little is known about the risk factors for cancer of unknown primary site (CUP). We examined the demographic, social and lifestyle risk factors for CUP in a prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia. METHODS: Baseline questionnaire data were linked to cancer registration, hospitalisation, emergency department admission, and mortality data. We compared individuals with incident cancer registry-notified CUP (n = 327) to two sets of controls randomly selected (3:1) using incidence density sampling with replacement: (i) incident cancer registry-notified metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In a fully adjusted model incorporating self-rated overall health and comorbidity, people diagnosed with CUP were more likely to be older (OR 1.05, 95% CI 1.04-1.07 per year) and more likely to have low educational attainment (OR 1.77, 95% CI 1.24-2.53) than those diagnosed with metastatic cancer of known primary. Similarly, compared to general cohort population controls, people diagnosed with CUP were older (OR 1.10, 95% CI 1.08-1.12 per year), of low educational attainment (OR 1.69, 95% CI 1.08-2.64), and current (OR 3.42, 95% CI 1.81-6.47) or former (OR 1.95, 95% CI 1.33-2.86) smokers. CONCLUSION: The consistent association with educational attainment suggests low health literacy may play a role in CUP diagnosis. These findings highlight the need to develop strategies to achieve earlier identification of diagnostically challenging malignancies in people with low health literacy.

The Kintamani dog: genetic profile of an emerging breed from Bali, Indonesia.

The Kintamani dog is an evolving breed indigenous to the Kintamani region of Bali. Kintamani dogs cohabitate with feral Bali street dogs, although folklore has the breed originating 600 years ago from a Chinese Chow Chow. The physical and personality characteristics of the Kintamani dog make it a popular pet for the Balinese, and efforts are currently under way to have the dog accepted by the Federation Cynologique Internationale as a recognized breed. To study the genetic background of the Kintamani dog, 31 highly polymorphic short tandem repeat markers were analyzed in Kintamani dogs, Bali street dogs, Australian dingoes, and nine American Kennel Club (AKC) recognized breeds of Asian or European origin. The Kintamani dog was identical to the Bali street dog at all but three loci. The Bali street dog and Kintamani dog were most closely aligned with the Australian dingo and distantly related to AKC recognized breeds of Asian but not European origin. Therefore, the Kintamani dog has evolved from Balinese feral dogs with little loss of genetic diversity.

The genetics of epilepsy in the Belgian tervuren and sheepdog.

Idiopathic epilepsy is characterized by recurrent seizure activity without an identifiable underlying anatomic defect. Dogs experiencing repeated bouts of severe seizures are given therapeutic medication to control their frequency and severity. Idiopathic epilepsy has been reported in many dog breeds and was identified as the predominant health issue facing dog breeds in a recent survey by the American Kennel Club. A growing body of evidence supports a hereditary basis for idiopathic epilepsy, with a variety of genetic inheritance models proposed. In the Belgian tervuren and sheepdog, epilepsy is highly heritable with a polygenic mode of inheritance, though apparently influenced by a single autosomal recessive locus of large effect. In an effort to establish molecular linkage between the epileptic phenotype and the locus of large effect, we have screened genomic DNA from families of affected tervuren and sheepdogs with 100 widely dispersed, polymorphic canine microsatellite markers (0.595 average PIC value). Although not significant (LOD scores <3.0), three genomic regions have shown nominal linkage between markers and the epileptic phenotype. Additional related dogs are being screened with these and additional markers to increase the power to detect the presence of a linked locus.

Analysis of genetic variation in 28 dog breed populations with 100 microsatellite markers.

Dog breeds were created by man choosing for select phenotypic traits such as size, shape, coat color, conformation, and behavior. Rigorous phenotypic selection likely resulted in a loss of genetic information. The present study extends previous dog population observations by assessing the genotypic variation within and across 28 breeds representing the seven recognized breed groups of the American Kennel Club (AKC). One hundred autosomal microsatellite markers distributed across the canine genome were used to examine variation within breeds. Resulting breed-specific allele frequencies were then used in an attempt to elucidate phylogeny and genetic distances between breeds. While the set of autosomal microsatellites was useful in describing genetic variation within breeds, establishing the genetic relatedness between breeds was less conclusive. A more accurate determination of breed phylogeny will likely require the use of single-nucleotide polymorphisms (SNPs).

Alternatives to blood as a source of DNA for large-scale scanning studies of canine genome linkages.

Participation and compliance are critical to the success of any large-scale study of canine disease using DNA markers. Most canine genetic studies rely upon DNA extracted from peripheral blood samples. We assessed the utility of buccal swab epithelial cells and toe nails as a source of DNA for use in genomic screening studies. Using eight multiplexed canine microsatellite markers, amplified DNA obtained from peripheral blood, and from freshly extracted buccal epithelial cells, and buccal swab DNA extracted and stored at 20 degrees C for 27 months or extracted from toe nails were compared for three dogs. The accuracy of the genotyping at each locus was identical for each preparation. Buccal swab DNA samples were readily and uniformly amplified and could be stored for years without loss of integrity. Each buccal swab provided sufficient DNA for more than 200 individual PCR reactions. Toe nails provided ample DNA for thousands of PCR reactions and had the added advantage of ease of storage of the original tissues. These studies demonstrate the potential utility of DNA derived from buccal swabs or nails in large-scale genomic scanning and marker linkage studies.

PCR multiplexed microsatellite panels to expedite canine genetic disease linkage analysis.

Modern dog breeds possess large numbers of genetic diseases for which there are currently few candidate genes or diagnostic tests. Linkage of a microsatellite marker to a disease phenotype is often the only available tool to aid in the development of screening tests for disease carriers. Detection of linkage to a specific disease phenotype requires screening of large numbers of markers across known affected and unaffected animals. To establish high throughput genome scanning this study placed 100 canine microsatellite markers, arranged by fragment size and fluorescent dye label, into 12 PCR multiplexed panels. The highest degree of multiplexing was 11 markers per panel while the lowest was five markers per panel; each panel was run in one gel lane on automated DNA sequencers. Selection of the markers was based upon chromosomal or linkage group locations, degree of polymorphism, PCR multiplex compatibility and ease of interpretation. The marker set has an average spacing of 22.25 centiMorgan (cM). Marker polymorphism was evaluated across 28 American Kennel Club (AKC) recognized breeds. The utility of buccal swab vs. blood samples was also validated in this study as all template DNA was derived from swabs obtained and submitted by participating dog breeders and owners. The PCR multiplexed microsatellite panels and sampling method described in this report will provide investigators with a cost effective and expedient means of pursuing linkage studies of specific canine genetic diseases.