Impact of colon cancer screening on family history phenotype.
ABSTRACT: If effective cancer screening is more common in people with a family history of cancer, the relationship between family history and cancer incidence may become distorted.To assess the impact of screening on the association between colorectal cancer family history and risk of colorectal cancer, we developed a model to simulate screening patterns in those with and without a family history.The introduction of screening reduces the apparent risk of colorectal cancer associated with family history in subsequent generations. This reduction becomes more pronounced as the difference in the uptake of screening between those with a family history and those without becomes larger.A result of effective screening is that observed family history of colorectal cancer may no longer match inherited risk, and observed family history may fail to be a strong risk factor. This may have implications for exposure-disease relationships if screening is differentially associated with the exposure.
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:To compare screening practices and beliefs in patients with and without a clinically important family history.We mailed a brief questionnaire asking about family history and a second, longer survey asking about knowledge of and beliefs about colorectal cancer to all respondents with a family history and a random sample of respondents without a family history of colorectal cancer. We reviewed electronic medical records for screening examinations and recording of family history.One thousand eight hundred seventy of 6,807 randomly selected patients ages 35-55 years who had been continuously enrolled in a large multispecialty group practice for at least 5 years.Recognition of increased risk, screening practices, and beliefs-all according to strength of family history and patient's age.Nineteen percent of respondents reported a family history of colorectal cancer. In 11%, this history was strong enough to warrant screening before age 50 years. However, only 39% (95% CI 36, 42) of respondents under the age of 50 years said they had been asked about family history and only 45% of those with a strong family history of colorectal cancer had been screened appropriately. Forty-six percent of patients with a strong family history did not know that they should be screened at a younger age than average risk people. Medical records mentioned family history of colorectal cancer in 59% of patients reporting a family history.More efforts are needed to translate information about family history of colorectal cancer into the care of patients.
Project description:BACKGROUND:Colorectal cancer is the fourth most commonly diagnosed cancer in the United States. Approximately 3-10% of the population has an increased risk for colorectal cancer due to family history and warrants more frequent or intensive screening. Yet, <?50% of that high-risk population receives guideline-concordant care. Systematic collection of family health history and decision support may improve guideline-concordant screening for patients at increased risk of colorectal cancer. We seek to test the effectiveness of a web-based, systematic family health history collection tool and decision support platform (MeTree) to improve risk assessment and appropriate management of colorectal cancer risk among patients in the Department of Veterans Affairs primary care practices. METHODS:In this ongoing randomized controlled trial, primary care providers at the Durham Veterans Affairs Health Care System and the Madison VA Medical Center are randomized to immediate intervention or wait-list control. Veterans are eligible if assigned to enrolled providers, have an upcoming primary care appointment, and have no conditions that would place them at increased risk for colorectal cancer (such as personal history, adenomatous polyps, or inflammatory bowel disease). Those with a recent lower endoscopy (e.g. colonoscopy, sigmoidoscopy) are excluded. Immediate intervention patients put their family health history information into a web-based platform, MeTree, which provides both patient- and provider-facing decision support reports. Wait-list control patients access MeTree 12?months post-consent. The primary outcome is the risk-concordant colorectal cancer screening referral rate obtained via chart review. Secondary outcomes include patient completion of risk management recommendations (e.g. colonoscopy) and referral for genetic consultation. We will also conduct an economic analysis and an assessment of providers' experience with MeTree clinical decision support recommendations to inform future implementation efforts if the intervention is found to be effective. DISCUSSION:This trial will assess the feasibility and effectiveness of patient-collected family health history linked to decision support to promote risk-appropriate screening in a large healthcare system such as the Department of Veterans Affairs. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02247336 . Registered on 25 September 2014.
Project description:OBJECTIVE:To explore the risk of colorectal cancer in family members of patients with colorectal cancer, with an emphasis on subtypes of second degree relatives, especially half siblings, which were lacking in the literature. DESIGN:Ambidirectional cohort study. SETTING:Nationwide Swedish Family Cancer Data (record linkage). PARTICIPANTS:All people residing in Sweden and born after 1931, with their biological parents, totalling >16 million individuals (follow-up: 1958-2015); of those with clear genealogy, 173?796 developed colorectal cancer. MAIN OUTCOME MEASURES:Lifetime (0-79 years) cumulative risk and standardised incidence ratio of colorectal cancer among first degree relatives and second degree relatives. RESULTS:The overall lifetime cumulative risk of colorectal cancer in siblings of patients was 7%, which represents a 1.7-fold (95% confidence interval 1.6 to 1.7; n=2089) increase over the risk in those without any family history of colorectal cancer. A similarly increased lifetime cumulative risk (6%) was found among half siblings (standardised incidence ratio 1.5, 95% confidence interval 1.3 to 1.8; n=140). The risk in people with colorectal cancer in both a parent and a half sibling (standardised incidence ratio 3.6, 2.4 to 5.0; n=32) was close to the risk in those with both an affected parent and an affected sibling (2.7, 2.4 to 3.0; n=396). Family history of colorectal cancer in only one second degree relative other than a half sibling (without any affected first degree relatives), such as a grandparent, uncle, or aunt, showed minor association with the risk of colorectal cancer. CONCLUSION:Family history of colorectal cancer in half siblings is similarly associated with colorectal cancer risk to that in siblings. The increase in risk of colorectal cancer among people with one affected second degree relative was negligible, except for half siblings, but the risk was substantially increased for a combination of family history in one affected second degree relative and an affected first degree relative (or even another second degree relative). These evidence based findings provide novel information to help to identify people at high risk with a family history of colorectal cancer that can potentially be used for risk adapted screening.
Project description:BACKGROUND:There is growing evidence for personalizing colorectal cancer screening based on risk factors. We compared the cost-effectiveness of personalized colorectal cancer screening based on polygenic risk and family history to uniform screening. METHODS:Using the MISCAN-Colon model, we simulated a cohort of 100 million 40-year-olds, offering them uniform or personalized screening. Individuals were categorized based on polygenic risk and family history of colorectal cancer. We varied screening strategies by start age, interval and test and estimated costs, and quality-adjusted life years (QALY). In our analysis, we (i) assessed the cost-effectiveness of uniform screening; (ii) developed personalized screening scenarios based on optimal screening strategies by risk group; and (iii) compared the cost-effectiveness of both. RESULTS:At a willingness-to-pay threshold of $50,000/QALY, the optimal uniform screening scenario was annual fecal immunochemical testing (FIT) from ages 50 to 74 years, whereas for personalized screening the optimal screening scenario consisted of annual and biennial FIT screening except for those at highest risk who were offered 5-yearly colonoscopy from age 50 years. Although these scenarios gained the same number of QALYs (17,887), personalized screening was not cost-effective, costing an additional $428,953 due to costs associated with determining risk (assumed to be $240 per person). Personalized screening was cost-effective when these costs were less than ?$48. CONCLUSIONS:Uniform colorectal cancer screening currently appears more cost-effective than personalized screening based on polygenic risk and family history. However, cost-effectiveness is highly dependent on the cost of determining risk. IMPACT:Personalized screening could become increasingly viable as costs for determining risk decrease.
Project description:BACKGROUND: Mortality associated with colorectal cancer can be reduced by early detection. However, the participation of eligible people in colorectal cancer screening is thought to be inadequate. We examined the frequency of colorectal cancer screening in 4 Canadian provinces and the influence of patient contact with a family physician on the uptake of cancer screening. METHODS: We performed analyses using data from the 2003 Canadian Community Health Survey. The study population included 12,776 people at average risk for colon cancer living in British Columbia, Saskatchewan, Ontario, and Newfoundland and Labrador who were aged 50 years or older and who were eligible for colorectal cancer screening. We assessed the proportion of respondents who reported having previous colorectal cancer screening tests and the degree of contact with a family physician. RESULTS: The provincial response rates for the survey were 78.5%-87.0%. The proportion of respondents who reported any history of colorectal cancer screening was 23.5%. This value dropped to 17.6% when only up-to-date screening was considered (screening within the time frame recommended in guidelines). The proportion of people with up-to-date colorectal cancer screening varied significantly among provinces, but it was low in all provinces sampled. Contact with a family physician was associated with increased colorectal cancer screening. Compared with no physician contact, the odds of screening associated with 1-2 physician contacts in the 12 months before the survey was 1.97 (95% confidence interval [CI] 1.56-2.48], and the odds of screening associated with more than 4 contacts was 2.75 (95% CI 2.14-3.53). INTERPRETATION: Self-reported colorectal cancer screening falls well below acceptable levels. People with increased contact with a family physician are more likely than those without contact to report a history of up-to-date colorectal cancer screening.
Project description:BACKGROUND:The Australian National Bowel Cancer Screening Programme (NBCSP) was introduced in 2006. When fully implemented, the programme will invite people aged 50 to 74 to complete an immunochemical faecal occult blood test (iFOBT) every 2 years. METHODS AND FINDINGS:To investigate colorectal cancer (CRC) screening occurring outside of the NBCSP, we classified participants (n = 2,480) in the Australasian Colorectal Cancer Family Registry (ACCFR) into 3 risk categories (average, moderately increased, and potentially high) based on CRC family history and assessed their screening practices according to national guidelines. We developed a microsimulation to compare hypothetical screening scenarios (70% and 100% uptake) to current participation levels (baseline) and evaluated clinical outcomes and cost for each risk category. The 2 main limitations of this study are as follows: first, the fact that our cost-effectiveness analysis was performed from a third-party payer perspective, which does not include indirect costs and results in overestimated cost-effectiveness ratios, and second, that our natural history model of CRC does not include polyp sojourn time, which determines the rate of cancerous transformation. Screening uptake was low across all family history risk categories (64%-56% reported no screening). For participants at average risk, 18% reported overscreening, while 37% of those in the highest risk categories screened according to guidelines. Higher screening levels would substantially reduce CRC mortality across all risk categories (95 to 305 fewer deaths per 100,000 persons in the 70% scenario versus baseline). For those at average risk, a fully implemented NBCSP represented the most cost-effective approach to prevent CRC deaths (AUS$13,000-16,000 per quality-adjusted life year [QALY]). For those at moderately increased risk, higher adherence to recommended screening was also highly cost-effective (AUS$19,000-24,000 per QALY). CONCLUSION:Investing in public health strategies to increase adherence to appropriate CRC screening will save lives and deliver high value for money.
Project description:BACKGROUND: The incidence of colorectal cancer can be decreased by appropriate use of screening modalities. Patients with a family history of colon cancer and of African-American ethnicity are known to be at higher risk of developing colorectal cancer. We aimed to determine if there is a lack of physician knowledge for colorectal cancer screening guidelines based on family history and ethnicity. Between February and April 2009 an anonymous web-based survey was administered to a random sample selected from a national list of 25,000 internists, family physicians and gastroenterologists. A stratified sampling strategy was used to include practitioners from states with high as well as low CRC incidence. All data analyses were performed following data collection in 2009. RESULTS: The average knowledge score was 37 ± 18% among the 512 respondents. Gastroenterologists averaged higher scores compared to internists, and family physicians, p = 0.001. Only 28% of physicians correctly identified the screening initiation point for African-Americans while only 12% of physicians correctly identified the screening initiation point and interval for a patient with a family history of CRC. The most commonly cited barriers to referring high-risk patients for CRC screening were "patient refusal" and "lack of insurance reimbursement." CONCLUSIONS: There is a lack of knowledge amongst physicians of the screening guidelines for high-risk populations, based on family history and ethnicity. Educational programs to improve physician knowledge and to reduce perceived barriers to CRC screening are warranted to address health disparities in colorectal cancer.
Project description:First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ?60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer).This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer ("familial-risk group") and 3,038 as asymptomatic with average-risk for colorectal cancer ("average-risk group"). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ?60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36-2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ?60 y (OR 1.03; 95% CI 0.83-1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90-1.58, p = 0.20). After the age of 50 y, men developed advanced neoplasia over two times more frequently than women and advanced neoplasia appeared at least ten y earlier. Fewer colonoscopies by 2-fold were required to detect one advanced neoplasia in men than in women. Major limitations of this study were first that although average-risk individuals were consecutively included in a randomized control trial, this was not the case for all individuals in the familial-risk cohort; and second, the difference in age between the average-risk and familial-risk cohorts.Individuals having two FDR with colorectal cancer showed an increased risk of advanced neoplasia compared to those with average-risk for colorectal cancer. Men had over 2-fold higher risk of advanced neoplasia than women, independent of family history. These data suggest that screening colonoscopy guidelines should be revised in the familial-risk population.
Project description:BACKGROUND & AIMS:Guidelines for initiating colorectal cancer (CRC) screening are based on family history but do not consider lifestyle, environmental, or genetic risk factors. We developed models to determine risk of CRC, based on lifestyle and environmental factors and genetic variants, and to identify an optimal age to begin screening. METHODS:We collected data from 9748 CRC cases and 10,590 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colorectal Transdisciplinary study, from 1992 through 2005. Half of the participants were used to develop the risk determination model and the other half were used to evaluate the discriminatory accuracy (validation set). Models of CRC risk were created based on family history, 19 lifestyle and environmental factors (E-score), and 63 CRC-associated single-nucleotide polymorphisms identified in genome-wide association studies (G-score). We evaluated the discriminatory accuracy of the models by calculating area under the receiver operating characteristic curve values, adjusting for study, age, and endoscopy history for the validation set. We used the models to project the 10-year absolute risk of CRC for a given risk profile and recommend ages to begin screening in comparison to CRC risk for an average individual at 50 years of age, using external population incidence rates for non-Hispanic whites from the Surveillance, Epidemiology, and End Results program registry. RESULTS:In our models, E-score and G-score each determined risk of CRC with greater accuracy than family history. A model that combined both scores and family history estimated CRC risk with an area under the receiver operating characteristic curve value of 0.63 (95% confidence interval, 0.62-0.64) for men and 0.62 (95% confidence interval, 0.61-0.63) for women; area under the receiver operating characteristic curve values based on only family history ranged from 0.53 to 0.54 and those based only E-score or G-score ranged from 0.59 to 0.60. Although screening is recommended to begin at age 50 years for individuals with no family history of CRC, starting ages calculated based on combined E-score and G-score differed by 12 years for men and 14 for women, for individuals with the highest vs the lowest 10% of risk. CONCLUSIONS:We used data from 2 large international consortia to develop CRC risk calculation models that included genetic and environmental factors along with family history. These determine risk of CRC and starting ages for screening with greater accuracy than the family history only model, which is based on the current screening guideline. These scoring systems might serve as a first step toward developing individualized CRC prevention strategies.