Biomedical subjects

Polly Newcomb

Publications and source records attributed to Polly Newcomb.

6 recordsLinked to original sources

PubMed2005

Identifying target populations for screening or not screening using logic regression.

Colorectal cancer remains a significant public health concern despite the fact that effective screening procedures exist and that the disease is treatable when detected at early stages. Numerous risk factors for colon cancer have been identified, but none are very predictive alone. We sought to determine whether there are certain combinations of risk factors that distinguish well between cases and controls, and that could be used to identify subjects at particularly high or low risk of the disease to target screening. Using data from the Seattle site of the Colorectal Cancer Family Registry, we fit logic regression models to combine risk factor information. Logic regression is a methodology that identifies subsets of the population, described by Boolean combinations of binary coded risk factors. This method is well suited to situations in which interactions between many variables result in differences in disease risk. We found that neither the logic regression models nor stepwise logistic regression models fit for comparison resulted in criteria that could be used to direct subjects to screening. However, we believe that our novel statistical approach could be useful in settings where risk factors do discriminate between cases and controls, and illustrate this with a simulated data set.

Adult↗

PubMed2005

Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X.

CONTEXT: Approximately 60% of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown. OBJECTIVE: To determine if cancer risks in AC-I families with no apparent deficiency in DNA MMR are different from cancer risks in AC-I families with DNA MMR abnormalities. DESIGN, SETTING, AND PARTICIPANTS: Identification (1997-2001) of 161 AC-I pedigrees from multiple population- and clinic-based sources in North America and Germany, with families grouped into those with (group A) or without (group B) MMR deficiency by tumor testing. A total of 3422 relatives were included in the analyses. MAIN OUTCOME MEASURES: Cancer incidence in groups A and B (excluding the 3 affected members used to define each pedigree as AC-I) and computed age- and sex-adjusted standardized incidence ratios (SIRs) using Surveillance, Epidemiology, and End Results data. RESULTS: Group A families from both population- and clinic-based series showed increased incidence of the HNPCC-related cancers. Group B families showed increased incidence only for colorectal cancer (SIR, 2.3; 95% confidence interval, 1.7-3.0) and to a lesser extent than group A (SIR, 6.1; 95% confidence interval, 5.2-7.2) (P<.001). CONCLUSIONS: Families who fulfill AC-I criteria but who have no evidence of a DNA MMR defect do not share the same cancer incidence as families with HNPCC-Lynch syndrome (ie, hereditary MMR deficiency). Relatives in such families have a lower incidence of colorectal cancer than those in families with HNPCC-Lynch syndrome, and incidence may not be increased for other cancers. These families should not be described or counseled as having HNPCC-Lynch syndrome. To facilitate distinguishing these entities, the designation of "familial colorectal cancer type X" is suggested to describe this type of familial aggregation of colorectal cancer.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Family history assessment to detect increased risk for colorectal cancer: conceptual considerations and a preliminary economic analysis.

BACKGROUND: Although the rationale for earlier screening of persons with a family history of colorectal cancer is plausible, there is no direct evidence that earlier assessment is either effective or cost-effective. OBJECTIVE: To estimate the clinical and economic effect of using family history assessment to identify persons for colorectal cancer screening before age 50. METHODS: We developed a decision model to compare costs and outcomes for two scenarios: (a) standard population screening starting at age 50; (b) family history assessment at age 40, followed by screening colonoscopy at age 40 for those with a suggestive family history of colorectal cancer. The analysis was conducted using the health insurer perspective. RESULTS: Using U.S. population estimates, 22 million would be eligible for family history assessment, and one million would be eligible for early colonoscopy; 2,834 invasive cancers would be detected, and 29,331 life years would be gained. The initial program cost would be USD $900 million. The discounted cost per life year gained of family history assessment versus no assessment equals USD $58,228. The results were most sensitive to the life expectancy benefit from earlier screening, the cost of colonoscopy, and the relative risk of colon cancer in those with a family history. CONCLUSIONS: The cost-effectiveness of family history assessment for colorectal cancer approaches that of other widely accepted technologies; yet, the results are sensitive to several assumptions where better data are needed. Because of the relatively high prevalence of family history in the population, careful analysis and empirical data are needed.

Adult↗

PubMed2004

Limitations of the odds ratio in gauging the performance of a diagnostic, prognostic, or screening marker.

A marker strongly associated with outcome (or disease) is often assumed to be effective for classifying persons according to their current or future outcome. However, for this assumption to be true, the associated odds ratio must be of a magnitude rarely seen in epidemiologic studies. In this paper, an illustration of the relation between odds ratios and receiver operating characteristic curves shows, for example, that a marker with an odds ratio of as high as 3 is in fact a very poor classification tool. If a marker identifies 10% of controls as positive (false positives) and has an odds ratio of 3, then it will correctly identify only 25% of cases as positive (true positives). The authors illustrate that a single measure of association such as an odds ratio does not meaningfully describe a marker's ability to classify subjects. Appropriate statistical methods for assessing and reporting the classification power of a marker are described. In addition, the serious pitfalls of using more traditional methods based on parameters in logistic regression models are illustrated.

Biomarkers↗

PubMed2003

Attitudes towards genetic screening for predisposition to colon cancer among cancer patients, their relatives and members of the community. Results of focus group interviews.

OBJECTIVE: To compare knowledge of and interest in genetic testing for hereditary colon cancer syndromes. METHODS: Colorectal cancer patients, first-degree relatives of colon cancer patients and controls were recruited from a familial cancer registry. Focus groups explored attitudes about genetic testing. RESULTS: All three groups conveyed interest in testing, but lacked knowledge about testing and its implications. After receiving information regarding the potential benefits and costs of testing (including insurance and employment issues) all three groups were disinclined to be tested. The reasons varied among risk groups. CONCLUSIONS: When informed about the costs and implications of testing, individuals may be reluctant to undergo genetic testing, regardless of baseline risk. Barriers to testing will vary depending on the perceived risk of carrying a mutation.

Colorectal Neoplasms↗

PubMed2002

Hormone replacement therapy in relation to breast cancer.

CONTEXT: Studies of long-term hormone replacement therapy (HRT) suggest an associated increased risk of breast cancer, but whether this association differs according to histologic type of cancer has not been extensively studied. OBJECTIVE: To determine whether the association between HRT and risk of breast cancer varies by HRT formulation and differs across histologic cancer types. DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study among 705 postmenopausal women enrolled in the Group Health Cooperative of Puget Sound (GHC) who were aged 50 to 74 years and had primary invasive breast cancer diagnosed between July 1, 1990, and December 31, 1995 (cases), and 692 randomly selected aged-matched female members of GHC (controls). MAIN OUTCOME MEASURE: Incidence and type of breast cancer by duration of HRT use in the 5-year period ending 1 year before diagnosis, which was ascertained from computerized pharmacy records. RESULTS: The incidence of breast cancer, all histologic types combined, was increased by 60% to 85% in recent long-term users of HRT, whether estrogen alone or estrogen plus progestin. Longer use of HRT (odds ratio [OR], 3.07 for 57 months or more; 95% confidence interval [CI], 1.55-6.06) and current use of combination therapy (OR, 3.91; 95% CI, 2.05-7.44) were associated with increased risk of lobular breast cancer. Long-term HRT use was associated with a 50% increase in nonlobular cancer (OR, 1.52 for 57 months or more; 95% CI, 1.01-2.29). CONCLUSION: Our data add to the growing body of evidence that recent long-term use of HRT is associated with an increased risk of breast cancer and that such use may be related particularly to lobular tumors.

Aged↗