Patient medical records are often fragmented across disparate healthcare databases, potentially resulting in duplicate records that may be detrimental to health care services. These duplicate records ...can be found through a process called record linkage. This paper describes a set of duplicate records in a medical data warehouse found by linking to an external resource containing family history and vital records. Our objective was to investigate the impact database characteristics and linkage methods have on identifying duplicate records using an external resource. Frequency counts were made for demographic field values and compared between the set of duplicate records, the data warehouse, and the external resource. Considerations for understanding the relationship that records labeled as duplicates have with dataset characteristics and linkage methods were identified. Several noticeable patterns were identified where frequency counts between sets deviated from what was expected including how the growth of a minority population affected which records were identified as duplicates. Record linkage is a complex process where results can be affected by subtleties in data characteristics, changes in data trends, and reliance on external data sources. These changes should be taken into account to ensure any anomalies in results describe real effects and are not artifacts caused by datasets or linkage methods. This paper describes how frequency count analysis can be an effective way to detect and resolve anomalies in linkage results and how external resources that provide additional contextual information can prove useful in discovering duplicate records.
A method is described for estimating excess relative risks of a disease from familial factors. Beginning with population-based series of cases and controls, a cohort of each subject's relatives is ...formed and checked for disease against a population based registry. The disease experience of the cohort formed from each subject's relatives is summarized as a kinship-weighted familial standardized incidence ratio (FSIR). The FSIR's are used as exposure estimates in conditional linear excess relative risk models, which may be used not only to screen for significant familial disease aggregations, but also to estimate relative risks, population attributable risks, and gene-environment interactions. The method is demonstrated on 4083 breast cancer cases from Utah and a set of matched controls.
Myosin-X (Myo10) is an unconventional myosin with MyTH4-FERM domains that is best known for its striking localization to the tips of filopodia and its ability to induce filopodia. Although the head ...domain of Myo10 enables it to function as an actin-based motor, its tail contains binding sites for several molecules with central roles in cell biology, including phosphatidylinositol (3,4,5)-trisphosphate, microtubules and integrins. Myo10 also undergoes fascinating long-range movements within filopodia, which appear to represent a newly recognized system of transport. Myo10 is also unusual in that it is a myosin with important roles in the spindle, a microtubule-based structure. Exciting new studies have begun to reveal the structure and single-molecule properties of this intriguing myosin, as well as its mechanisms of regulation and induction of filopodia. At the cellular and organismal level, growing evidence demonstrates that Myo10 has crucial functions in numerous processes ranging from invadopodia formation to cell migration.
The impact of family history of colon cancer on survival after diagnosis with colon cancer is generally unknown. It is possible that family history is indicative of a genetically inherited form of ...disease which may alter survival.
The Utah Population Database was used to evaluate survival after diagnosis with colon cancer among 2236 first primary colon cancer cases. This database includes detailed information about family history and is linked to the Utah Cancer Registry to obtain tumour information.
Stage at diagnosis was the primary factor associated with death from all causes and from colon cancer. An older age at diagnosis, being female, and having a tumour in the ascending segment of the colon also were associated with poorer survival, although after adjusting for stage at diagnosis these associations disappeared. Having a family history of colon cancer had little impact on survival patterns although there were suggestions that men who were diagnosed at age < or = 55 were more likely to die from all causes as well as colon cancer if they had a sibling with colon cancer (hazard rate ratio HRR 2.50, 95% confidence interval CI: 1.03-6.10) relative to men > 55 without a sibling with colon cancer.
From these data it appears that the major factor which increases survival is being diagnosed at an early stage of disease. These data also suggest that younger men who have a sibling with colon cancer may have a different form of colon cancer which increases their risk of dying.
Abstract
Methylenetetrahydrofolate reductase(MTHFR) is a key enzyme in folate metabolism that is critical for DNA methylation, synthesis and repair. Since genetic polymorphisms may modify the ...efficiency of this enzyme, we tested the hypothesis that MTHFR modifies breast cancer (BC) survival using data from the Health, Eating, Activity and Lifestyle (HEAL) Study for 772 incident primary invasive cases (Stage I-IIIA). Over the 5-year follow-up there were 50 women diagnosed with a recurrence and 39 with a new primary. Over 7-years of follow-up, there were 160 deaths; 97 due to BC. In Cox proportional-hazards analysis, carriers of variant alleles of MTHFR polymorphisms, C677T (HR = 0.76, 95% confidence interval CI: 0.51, 1.14) and A1298C (HR = 0.66, 95% CI: 0.44, 1.00), had reduced mortality rates, adjusting for ER status and stage. In women with more severe disease who received chemotherapy, the HR was 5.6(95% CI: 2.8-10.9) for those without the T allele, and 4.3(95% CI: 2.1-9.1) for those with it present (p = 0.09) compared to those without the T allele and no chemotherapy treatment (Table 1). No interaction with chemotherapy was observed for A1298C. C677T may modify the association of chemotherapy in predicting BC survival. There is strong linkage disequilibrium between C677T and A1298C (Lewontin's D’ = 0.94) suggesting two different inheritance patterns; however, recombination between them is documented to be rare. These results should be explored further in clinical populations. Study of interactions with other genes in the folate metabolism pathway (BHMT, TS, MTR, MTRR, SHMT) with BC survival is under investigation
Citation Format: {Authors}. {Abstract title} abstract. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2750. doi:10.1158/1538-7445.AM2011-2750
The TGF-beta signaling pathway has a significant role in breast cancer initiation and promotion by regulating various cellular processes. We evaluated whether genetic variation in eight genes ...(TGF-beta1, TGF-beta2, TGF-betaR1, TGF-betaR2, TGF-betaR3, RUNX1, RUNX2, and RUNX3)is associated with breast cancer risk in women from the Breast Cancer Health Disparities Study. A total of 3,524 cases (1,431 non-Hispanic whites (NHW); 2,093 Hispanics/Native Americans(NA)) and 4,209 population-based controls (1,599 NHWs; 2,610 Hispanics/NAs) were included in analyses. Genotypes for 47 single nucleotide polymorphisms (SNPs) were determined. Additionally, 104 ancestral informative markers estimated proportion of NA ancestry. Associations with breast cancer risk overall, by menopausal status, NA ancestry, and estrogen receptor (ER)/progesterone receptor tumor phenotype were evaluated. After adjustment for multiple comparisons, two SNPs were significantly associated with breast cancer risk: RUNX3 (rs906296 OR.sub.CG/GG = 1.15 95 % CI 1.04-1.26) and TGF-beta1 (rs4803455 OR.sub.CA/AA = 0.89 95 % CI 0.81-0.98). RUNX3 (rs906296) and TGF-betaR2 (rs3773644) were associated with risk in pre-menopausal women (p.sub.adj = 0.002 and 0.02, respectively) and in those with intermediate to high NA ancestry (p.sub.adj = 0.04 and 0.01, respectively). Self-reported race was strongly correlated with NA ancestry (r = 0.86). There was a significant interaction between NA ancestry and RUNXl (rs7279383, p.sub.adj = 0.04). Four RUNX SNPs were associated with increased risk of ER--tumors. Results provide evidence that genetic variation in TGF-beta and RUNX genes are associated with breast cancer risk. This is the first report of significant associations between genetic variants in TGF-beta and RUNX genes and breast cancer risk among women of NA ancestry. Keywords Breast cancer risk * Breast Cancer Health Disparities Study * TGF-beta signaling pathway * Native American ancestry * Hispanic * Non-Hispanic white
Background & Aims:
Microsatellite instability is a property of most tumors occurring in the context of hereditary nonpolyposis colon cancer. Instability also occurs in 10%–15% of apparently sporadic ...colorectal cancers, and it has been hypothesized that this instability may indicate a genetic predisposition to colonic cancer. This study evaluated whether there is a clinically useful association between colon cancer instability and a family history of cancer.
Methods:
Colon cancer cases (n = 188) from a population-based study were evaluated for microsatellite instability with 10 polymerase chain reaction primer sets. Instability results were compared with family history and other clinical and biological characteristics.
Results:
Microsatellite instability was found in 16.5% of tumors. It was predominantly a feature of right-sided tumors (
P = 0.003) and was associated with the youngest and oldest ages at diagnosis (
P = 0.01). Instability was not associated with family history of cancer, sex of the individual, or the glutathione-
S-transferase mu 1 null genotype.
Conclusions:
Although some very small, and as yet undefined, proportion of colon cancer may be caused by inherited mutations leading to microsatellite instability, tumoral instability by itself is not a marker for familiality and should not be considered as evidence for an inherited syndrome.
Misfolded alpha-synuclein (AS) and other neurodegenerative disorder proteins display prion-like transmission of protein aggregation. Factors responsible for the initiation of AS aggregation are ...unknown. To evaluate the role of amyloid proteins made by the microbiota we exposed aged rats and transgenic C. elegans to E. coli producing the extracellular bacterial amyloid protein curli. Rats exposed to curli-producing bacteria displayed increased neuronal AS deposition in both gut and brain and enhanced microgliosis and astrogliosis compared to rats exposed to either mutant bacteria unable to synthesize curli, or to vehicle alone. Animals exposed to curli producing bacteria also had more expression of TLR2, IL-6 and TNF in the brain than the other two groups. There were no differences among the rat groups in survival, body weight, inflammation in the mouth, retina, kidneys or gut epithelia, and circulating cytokine levels. AS-expressing C. elegans fed on curli-producing bacteria also had enhanced AS aggregation. These results suggest that bacterial amyloid functions as a trigger to initiate AS aggregation through cross-seeding and also primes responses of the innate immune system.
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