Dataset Information

Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study.

ABSTRACT:

Background

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).

Methods and findings

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.

Conclusions

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.

SUBMITTER: Quintero E

PROVIDER: S-EPMC4854417 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study.

Quintero Enrique E Carrillo Marta M Leoz Maria-Liz ML Cubiella Joaquin J Gargallo Carla C Lanas Angel A Bujanda Luis L Gimeno-García Antonio Z AZ Hernández-Guerra Manuel M Nicolás-Pérez David D Alonso-Abreu Inmaculada I Morillas Juan Diego JD Balaguer Francesc F Muriel Alfonso A

PLoS medicine 20160503 5

<h4>Background</h4>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 neo ...[more]

PMID: 27138769

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Project description:ObjectiveTo assess the risk of colorectal cancer (CRC) in first degree relatives (parents and full siblings) of patients with precursor lesions (polyps) for CRC.DesignCase-control study.SettingLinkage to the multi-generation register and gastrointestinal ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) histopathology cohort in Sweden.Participants68 060 patients with CRC and 333 753 matched controls.Main outcome measuresMultivariable adjusted odds ratios of CRC according to the number of first degree relatives with a colorectal polyp and the histology of polyps and age at diagnosis in first degree relatives. Subgroup analysis was also performed according to age at CRC diagnosis and evaluated the joint association of family history of colorectal polyps and family history of CRC.ResultsAfter adjusting for family history of CRC and other covariates, having a first degree relative with a colorectal polyp (8.4% (5742/68 060) in cases and 5.7% (18 860/333 753) in controls) was associated with a higher risk of CRC (odds ratio 1.40, 95% confidence interval 1.35 to 1.45). The odds ratios ranged from 1.23 for those with hyperplastic polyps to 1.44 for those with tubulovillous adenomas. To better put this risk in perspective, the age specific absolute risk of colon and rectal cancers was estimated according to family history of polyps based on the 2018 national CRC incidence in Sweden. For example, the absolute risk of colon cancer in individuals aged 60-64 years with and without a family history of colorectal polyp was, respectively, 94.3 and 67.9 per 100 000 for men and 89.1 and 64.1 per 100 000 for women. The association between family history of polyps and CRC risk was strengthened by the increasing number of first degree relatives with polyps (≥2 first degree relatives: 1.70, 1.52 to 1.90, P<0.001 for trend) and decreasing age at polyp diagnosis (<50 years: 1.77, 1.57 to 1.99, P<0.001 for trend). A particularly strong association was found for early onset CRC diagnosed before age 50 years (≥2 first degree relatives: 3.34, 2.05 to 5.43, P=0.002 for heterogeneity by age of CRC diagnosis). In the joint analysis, the odds ratio of CRC for individuals with two or more first degree relatives with polyps but no CRC was 1.79 (1.52 to 2.10), with one first degree relative with CRC but no polyps was 1.70 (1.65 to 1.76), and with two or more first degree relatives with both polyps and CRC was 5.00 (3.77 to 6.63) (P<0.001 for interaction).ConclusionsAfter adjusting for family history of CRC, the siblings and children of patients with colorectal polyps are still at higher risk of CRC, particularly early onset CRC. Early screening for CRC might be considered for first degree relatives of patients with polyps.

Project description:Studying sensorimotor and neurocognitive impairments in unaffected family members of individuals with autism may help identify familial pathophysiological mechanisms associated with the disorder.To determine whether atypical sensorimotor or neurocognitive characteristics associated with autism are present in first-degree relatives of individuals with autism.Case-control comparison of neurobehavioral functions.University medical center.Fifty-seven first-degree relatives of individuals with autism and 40 age-, sex-, and IQ-matched healthy control participants (aged 8-54 years).Oculomotor tests of sensorimotor responses (saccades and smooth pursuit); procedural learning and response inhibition; neuropsychological tests of motor, memory, and executive functions; and psychological measures of social behavior, communication skills, and obsessive-compulsive behaviors.On eye movement testing, family members demonstrated saccadic hypometria, reduced steady-state pursuit gain, and a higher rate of voluntary response inhibition errors relative to controls. They also showed lateralized deficits in procedural learning and open-loop pursuit gain (initial 100 milliseconds of pursuit) and increased variability in the accuracy of large-amplitude saccades that were confined to rightward movements. In neuropsychological studies, only executive functions were impaired relative to those of controls. Family members reported more communication abnormalities and obsessive-compulsive behaviors than controls. Deficits across oculomotor, neuropsychological, and psychological domains were relatively independent from one another.Family members of individuals with autism demonstrate oculomotor abnormalities implicating pontocerebellar and frontostriatal circuits and left-lateralized alterations of frontotemporal circuitry and striatum. The left-lateralized alterations have not been identified in other neuropsychiatric disorders and are of interest given atypical brain lateralization and language development associated with the disorder. Similar oculomotor deficits have been reported in individuals with autism, suggesting that they may be familial and useful for studies of neurophysiological and genetic mechanisms in autism.

Dataset Information

Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study.

Background

Methods and findings

Conclusions

Publications

Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study.

Similar Datasets

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