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Population-based family history-specific risks for colorectal cancer: a constellation approach.

ABSTRACT: Colorectal cancer (CRC) risk estimates based on family history typically include only close relatives. We report familial relative risk (FRR) in probands with various combinations, or constellations, of affected relatives, extending to third-degree.A population-based resource that includes a computerized genealogy linked to statewide cancer records was used to identify genetic relationships among CRC cases and their first-, second-, and third-degree relatives (FDRs, SDRs, and TDRs). FRRs were estimated by comparing the observed number of affected persons with a particular family history constellation to the expected number, based on cohort-specific CRC rates.A total of 2,327,327 persons included in > or =3 generation family histories were analyzed; 10,556 had a diagnosis of CRC. The FRR for CRC in persons with > or =1 affected FDR = 2.05 (95% CI, 1.96-2.14), consistent with published estimates. In the absence of a positive first-degree family history, considering both affected SDRs and TDRs, only 1 constellation had an FRR estimate that was significantly >1.0 (0 affected FDRs, 1 affected SDR, 2 affected TDRs; FRR = 1.33; 95% CI, 1.13-1.55). The FRR for persons with 1 affected FDR, 1 affected SDR, and 0 affected TDRs was 1.88 (95% CI, 1.59-2.20), increasing to FRR = 3.28 (95% CI, 2.44-4.31) for probands with 1 affected FDR, 1 affected SDR, and > or =3 affected TDRs.Increased numbers of affected FDRs influences risk much more than affected SDRs or TDRs. However, when combined with a positive first-degree family history, a positive second- and third-degree family history can significantly increase risk.

SUBMITTER: Taylor DP

PROVIDER: S-EPMC2831153 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Population-based family history-specific risks for colorectal cancer: a constellation approach.

Taylor David P DP Burt Randall W RW Williams Marc S MS Haug Peter J PJ Cannon-Albright Lisa A LA

Gastroenterology 20091221 3

<h4>Background & aims</h4>Colorectal cancer (CRC) risk estimates based on family history typically include only close relatives. We report familial relative risk (FRR) in probands with various combinations, or constellations, of affected relatives, extending to third-degree.<h4>Methods</h4>A population-based resource that includes a computerized genealogy linked to statewide cancer records was used to identify genetic relationships among CRC cases and their first-, second-, and third-degree rela ...[more]

PMID: 19932107

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Project description:BACKGROUND: With 14.234 diagnoses and over 4047 deaths reported in 2007, colorectal cancer (CRC) is the second most common cancer and second most common cause of cancer-related mortality in Australia. The direct treatment cost has recently been estimated to be around AU$1.2 billion for the year 2011, which corresponds to a four-fold increase, compared the cost reported in 2001. Excluding CRCs due to known rare genetic disorders, 20% to 25% of all CRCs occur in a familial aggregation setting due to genetic variants or shared environmental risk factors that are yet to be characterised. A targeted screening strategy addressed to this segment of the population is a potentially valuable tool for reducing the overall burden of CRC. METHODS: We developed a Markov model to assess the cost-effectiveness of three screening strategies offered to people at increased risk due to a strong family history of CRC. The model simulated the evolution of a cohort of 10,000 individuals from age 50 to 90 years. We compared screening with biennial iFOBT, five-yearly colonoscopy and ten-yearly colonoscopy versus the current strategy of the Australian National Bowel Cancer Screening Programme (i.e. base case). RESULTS: Under the NBCSP scenario, 6,491 persons developed CRC with an average screening lifetime cost of AU$3,441 per person. In comparison, screening with biennial iFOBT, colonoscopy every ten years, and colonoscopy every five years reduced CRC incidence by 27%, 35% and 60%, and mortality by 15%, 26% and 46% respectively. All three screening strategies had a cost under AU$50,000 per life year gained, which is regarded as the upper limit of acceptable cost-effectiveness in the Australian health system. At AU$12,405 per life year gained and an average lifetime expectancy of 16.084 years, five-yearly colonoscopy screening was the most cost-effective strategy. CONCLUSION: The model demonstrates that intensive CRC screening strategies targeting people at increased risk would be cost-effective in the Australian context. Our findings provide evidence that substantial health benefits can be generated from risk-based CRC screening at a relatively modest incremental cost.

Project description:ObjectivesLynch syndrome increases risks for colorectal and other cancers. Though published Lynch syndrome cancer risk-management guidelines are effective for risk-reduction, the condition remains under-recognized. The Cancer Genetics Program at an academic medical center implemented a population-based cancer family history screening program, Detecting Unaffected Individuals with Lynch syndrome, to aid in identification of individuals with Lynch syndrome.MethodsIn this retrospective cohort study, simple cancer family history screening questionnaires were used to identify those at risk for Lynch syndrome. Program navigators triaged and educated those who screened positive about hereditary cancer, and genetic counseling and testing services, offering genetic counseling if eligible. Genetic counseling was provided primarily via telephone. Genetic counselors performed hereditary cancer risk assessment and offered genetic testing via hereditary cancer panels to those eligible. Remote service delivery models via telephone genetic counseling and at-home saliva testing were used to increase access to medical genetics services.ResultsThis program screened 212,827 individuals, over half of whom were considered underserved, and identified 133 clinically actionable genetic variants associated with hereditary cancer. Of these, 47 (35%) were associated with Lynch syndrome while notably, 70 (53%) were not associated with hereditary colorectal cancer. Of 3,344 patients offered genetic counseling after initial triage, 2,441 (73%) elected to schedule the appointment and 1,775 individuals (73%) completed genetic counseling. Among underserved patients, telephone genetic counseling completion rates were significantly higher than in-person appointment completion rates (P < .05). While remote service delivery improved appointment completion rates, challenges with genetic test completion using at-home saliva sample collection kits were observed, with 242 of 1592 individuals (15%) not completing testing.ConclusionPopulation-based cancer family history screening and navigation can help identify individuals with hereditary cancer syndromes across diverse patient populations, but logistics of certain downstream service delivery models can impact outcomes.

Project description:Some cancers are largely preventable through modification of certain behavioral risk factors and preventive screening, even among those with a family history of cancer. This study examined the associations between (1) family cancer history and cancer screening, (2) family history and cancer preventive lifestyle behaviors, and (3) cancer screening and lifestyle behaviors.Data were from the 2009 California Health Interview Survey (n = 12,603). Outcomes included screening for breast cancer (BC) and colorectal cancer (CRC) and six cancer preventive lifestyle behaviors, based on World Cancer Research Fund recommendations. Multivariate logistic regression analyses, stratified by gender and race-ethnicity, examined associations. Predicted probabilities of cancer screening by family cancer history, race-ethnicity, and sex were computed.Family history of site-specific cancer-CRC for men and women, and BC for women-was associated with higher probability of cancer screening for most groups, especially for CRC, but was largely unrelated to other lifestyle behaviors. In the few cases in which family history was significantly associated with lifestyle-for example, physical activity among White and Latino males, smoking among White and Asian females-individuals with a family history had lower odds of adherence to recommendations than those with no family history. Greater overall adherence to lifestyle recommendations was associated with higher odds of up-to-date CRC screening among White and Asian males, and lower odds among Asian females (no significant association with BC screening); this relationship did not vary by family cancer history.The fact that family history of cancer is not associated with better lifestyle behaviors may reflect shared behavioral risks within families, or the lack of knowledge about how certain lifestyle behaviors impact personal cancer risk. Findings can inform interventions aimed at lifestyle behavioral modification for individuals at increased cancer risk due to family history.

Project description:Background & aimsLittle is known about the change in risk conferred by family history of colorectal cancer (CRC) as a person ages. We evaluated the effect of family history on CRC incidence and mortality after 55 years of age, when the risk of early onset cancer had passed.MethodsWe collected data from participants in the randomized, controlled Prostate, Lung, Colorectal and Ovarian cancer screening trial of flexible sigmoidoscopy versus usual care (55-74 years old, no history of CRC), performed at 10 US centers from 1993 to 2001. A detailed family history of colorectal cancer was obtained at enrollment, and subjects were followed for CRC incidence and mortality for up to 13 years.ResultsAmong 144,768 participants, 14,961 subjects (10.3%) reported a family of CRC. Of 2090 incident cases, 273 cases (13.1%) had a family history of CRC; among 538 deaths from CRC, 71 (13.2%) had a family history of CRC. Overall, family history of CRC was associated with an increased risk of CRC incidence (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10-1.50; P<.0001) and increased mortality (HR, 1.31; 95% CI, 1.02-1.69; P = .03). Subjects with 1 first degree relative (FDR) with CRC (n = 238; HR, 1.23; 95% CI, 1.07-1.42) or ≥2 FDRs with CRC (n = 35; HR, 2.04; 95% CI, 1.44-2.86) were at increased risk for incident CRC. However, among individuals with 1 FDR with CRC, there were no differences in risk based on age at diagnosis in the FDR (for FDR <60 years of age: HR, 1.27; 95% CI, 0.97-1.63; for FDR 60-70 years of age: HR, 1.33; 95% CI, 1.06-1.62; for FDR >70 years of age: HR, 1.14; 95% CI, 0.93-1.45; P trend = .59).ConclusionsAfter 55 years of age, subjects with 1 FDR with CRC had only a modest increase in risk for CRC incidence and death; age of onset in the FDR was not significantly associated with risk. Individuals with ≥2 FDRs with CRC had continued increased risk in older age. Guidelines and clinical practice for subjects with a family history of CRC should be modified to align CRC testing to risk. ClinicalTrials.gov number, NCT00002540.

Dataset Information

Population-based family history-specific risks for colorectal cancer: a constellation approach.

Publications

Population-based family history-specific risks for colorectal cancer: a constellation approach.

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