Do individuals with a family history of colorectal cancer adhere to medical recommendations for the prevention of colorectal cancer?

Individuals with a family history of colorectal cancer (CRC), have a two-to-five-fold increased lifetime risk to develop CRC. Thus, they are particularly likely to benefit from adherence to medical recommendations for CRC prevention. Despite this increased risk, previous studies have shown an underutilization of colonoscopy for screening and a paucity of data on lifestyle habits that could enhance colonoscopy rates in this population. The primary aims were (a) to assess CRC screening patterns and lifestyle choices among siblings and children of CRC patients, (b) to ascertain discrepancies between actual behavior and medical recommendations, and (c) to identify family members with multiple unhealthy lifestyle habits. The secondary aim was to test for possible associations between utilization rates for CRC screening and other preventive health services. A cross-sectional study was conducted among 318 first-degree relatives (FDRs) of 164 CRC patients treated at the Tel Aviv Sourasky Medical Center. Interviews were conducted with a structured questionnaire. There was significant underutilization of colonoscopy for screening with only 73 FDRs (23.0 %) adhering to the recommended screening schedule. This rate was slightly improved (N = 58, 31.9 %) among subjects aged 40 years and above, although it was still far below the optimum. A similar result (N = 70, 21.7 %) was observed for other cancer screening tests and routine medical check-ups. A significant association (P < 0.0001) was found for healthful lifestyles, overall use of preventive health services, and adherence to CRC screening recommendations. CRC screening is significantly underutilized among FDRs of CRC patients. FDRs who do not comply with CRC screening guidelines, lead unhealthy lifestyles, and avoid other cancer screening tests are at increased risk and should be addressed specifically in future interventions.     

How much colonoscopy screening should be recommended to individuals with various degrees of family history of colorectal cancer?

BACKGROUND:

Individuals with a family history of colorectal cancer (CRC) are at increased risk for CRC. Current screening recommendations for these individuals are based on expert opinion. The authors investigated optimal screening strategies for individuals with various degrees of family history of CRC based on a cost‐effectiveness analysis.

METHODS:

The MISCAN‐Colon microsimulation model was used to estimate costs and effects of CRC screening strategies, varying by the age at which screening was started and stopped and by screening interval. The authors defined 4 risk groups, characterized by the number of affected first‐degree relatives and their age at CRC diagnosis. For all risk groups, the optimal screening strategy had an incremental cost‐effectiveness ratio of approximately $50,000 per life‐year gained.

RESULTS:

The optimal screening strategy for individuals with 1 first‐degree relative diagnosed after age 50 years was 6 colonoscopies every 5 years starting at age 50 years, compared with 4 colonoscopies every 7 years starting at age 50 years for average risk individuals. The optimal strategy had 10 colonoscopies every 4 years for individuals with 1 first‐degree relative diagnosed before age 50 years, 13 colonoscopies every 3 years for individuals with 2 or more first‐degree relatives diagnosed after age 50 years, and 15 colonoscopies every 3 years for individuals with 2 or more first‐degree relatives of whom at least 1 was diagnosed before age 50 years.

CONCLUSIONS:

The optimal screening strategy varies considerably with the number of affected first‐degree relatives and their age of diagnosis. Shorter screening intervals than the currently recommended 5 years may be appropriate for the highest risk individuals. Cancer 2011;. © 2011 American Cancer Society.     

Breast cancer screening case–control study design: impact on breast cancer mortality

BackgroundRecent case–control studies on the effectiveness of population-based breast cancer screening show differences in the magnitude of breast cancer mortality reduction. We investigated the role played by aspects of the case–control study design on these differences, e.g. the definition of cases and exposure to screening.Material and methodsWe investigated six case–control studies conducted in East Anglia (UK), Wales, Iceland, central and northern Italy, South Australia and The Netherlands.ResultsThe breast cancer mortality reduction in the different case–control studies ranged from 38% to 70% in the screened versus the nonscreened women. We identified differences in design, e.g. the inclusion or exclusion of the first years of screening, and the correction factor for self-selection bias.ConclusionsOverall, the design of the case–control studies was similar. The differences in the magnitude of breast cancer mortality reductions are therefore unlikely to be caused by variations in the design of the case–control studies. These differences must be due to other factors, like the organisation of the service screening programme and the attendance rate. The reduction in breast cancer mortality estimated in these case–control studies indicates that the impact of current mammographic screening is at least consistent with the effect reported by the former randomised screening trials.     

The psychological impact of participating in colorectal cancer screening by faecal immuno-chemical testing – the Australian experience

Background:

Occult blood-based colorectal cancer (CRC) screening may result in adverse psychological outcomes for participants. The aims of this study were to measure the psychological consequences of participating in screening at key points along the screening and diagnostic pathway, and examine variation over time within or between test outcome groups.

Methods:

A total of 301 people (positives=165, negatives=136) aged 50–76 years were surveyed via validated psychological questionnaires after result notification, post colonoscopy (positives only) and 1 year following result notification.

Results:

Negatives scored significantly higher in quality of life domains and lower state anxiety, anger and depression in comparison to positives both after result notification and at 1 year follow-up. Positives had significantly decreased state anxiety and depression at 1 year and improvement in HLoC power and reduced screening decision doubtfulness post colonoscopy. Positives experienced heightened CRC risk perception both after result notification and at 1 year follow-up in comparison to negatives, but reported less difficulty participating in ongoing screening.

Conclusions:

In positives, increased anxiety and doubtfulness about the decision to screen declined over time. Lower CRC risk perception in negatives indicates the need for education to promote CRC screening participation.     

Prognostic impact of histological categorisation of epithelial–mesenchymal transition in colorectal cancer

Background:

The crosstalk between cancer cells and stroma is involved in the acquired capability for metastasis through the induction of epithelial–mesenchymal transition (EMT). We aimed to clarify the prognostic value of the histological category of EMT in colorectal cancer (CRC).

Methods:

Tumour EMT was graded into one of three histological categories on the basis of integrated assessment of poorly differentiated clusters and pro-EMT desmoplasia at the leading edge of the primary tumour (Histology^EMT). Stage II and III CRC patients (cohort 1, N=500) and stage IV patients (cohort 2, N=196) were retrospectively analysed.

Results:

In cohort 1, patients were stratified into three groups with widely different disease-free survival rates (95%, 83% and 39%) on the basis of Histology^EMT (P<0.0001). In cohort 2, Histology^EMT significantly stratified overall survival of patients irrespective of metasectomy. Multivariate analyses indicated that Histology^EMT had a strong prognostic impact independent of staging factors. Statistically, Histology^EMT had a better prognostic stratification power than T and N stages; however, in cohort 2, the power of M substage was superior.

Conclusions:

A histological model to categorise EMT by integrated assessment of dedifferentiation and desmoplastic environment is a potent prognostic index independent of staging factors.     

Accuracy of self-reported family history of cancer in a large case–control study of ovarian cancer

OBJECTIVE: To evaluate the reliability of self-reported family history of cancer in first-degree female relatives and to examine possible determinants of accurate reporting. METHODS: Women with ovarian cancer and controls were recruited between 1995 and 1999 and interviewed. The study comprised 579 cases and 1,564 controls with 6,265 first-degree female relatives. Self-reported familial cancer diagnoses were validated from registry data. Sensitivity, specificity, and kappa were calculated, and possible determinants were examined by logistic regression. RESULTS: The sensitivity of self-reporting ranged from 0.78 to 0.90 for all cancers but was lower for self-reporting of most site-specific cancers, ranging from 0.29 to 0.94. The specificity of self-reporting ranged from 0.91 to 0.99 for cancer in general and from 0.99 to 1.00 for site-specific cancers. Type of relative, age at interview, and length of education influenced the sensitivity and specificity significantly. The odds ratio for ovarian cancer was higher when based on registry data than on self-reported data and was significant (OR = 2.58 vs. 1.56). CONCLUSIONS: Cancer diagnoses in first-degree relatives are not always accurately reported by patients with ovarian cancer or by controls. The results indicate that studies of associations with family cancer history should validate self-reported family cancer diagnoses as carefully as possible.     

Early detection of cancer in the general population: a blinded case–control study of p53 autoantibodies in colorectal cancer

Background:

Recent reports from cancer screening trials in high-risk populations suggest that autoantibodies can be detected before clinical diagnosis. However, there is minimal data on the role of autoantibody signatures in cancer screening in the general population.

Methods:

Informative p53 peptides were identified in sera from patients with colorectal cancer using an autoantibody microarray with 15-mer overlapping peptides covering the complete p53 sequence. The selected peptides were evaluated in a blinded case–control study using stored serum from the multimodal arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening where women gave annual blood samples. Cases were postmenopausal women who developed colorectal cancer following recruitment, with 2 or more serum samples preceding diagnosis. Controls were age-matched women with no history of cancer.

Results:

The 50 640 women randomised to the multimodal group were followed up for a median of 6.8 (inter-quartile range 5.9–8.4) years. Colorectal cancer notification was received in 101 women with serial samples of whom 97 (297 samples) had given consent for secondary studies. They were matched 1 : 1 with 97 controls (296 serial samples). The four most informative peptides identified 25.8% of colorectal cancer patients with a specificity of 95%. The median lead time was 1.4 (range 0.12–3.8) years before clinical diagnosis.

Conclusion:

Our findings suggest that in the general population, autoantibody signatures are detectable during preclinical disease and may be of value in cancer screening. In colorectal cancer screening in particular, where the current need is to improve compliance, it suggests that p53 autoantibodies may contribute towards risk stratification.     

Screening younger women with a family history of breast cancer – does early detection improve outcome?

Women with a family history are often offered mammographic surveillance at an earlier age and with greater frequency than those in the National Breast Screening Programme. In this study, we compared the survival of 62 breast cancer patients diagnosed in the context of a family history clinic offering 12-18 monthly mammographic screening with that of 1108 patients of the same age range but having no exposure to screening. We subtracted the expected additional observation time due to lead time from the survival of the screen-detected cases. Survival was significantly better in the family history group with relative hazards of 0.19 (95% CI 0.07-0.52, P<0.001) for breast cancer death and 0.19 (95% CI 0.08-0.43, P<0.001) for disease-free survival. After correcting for lead-time, the relative hazards were 0.24 (95% CI 0.09-0.66, P=0.005) for breast cancer death and 0.25 (95% CI 0.11-0.57, P<0.001) for disease-free survival. These results strongly suggest that screening younger women with a family history of breast cancer leads to improved survival. More precise estimates of the benefit will accrue from further follow-up and other such studies.     

All in the family? Analyzing the impact of family history in addition to genotype on medullary thyroid carcinoma aggressiveness in MEN2A patients

Several guidelines for patients with multiple endocrine neoplasia 2A (MEN2A) take into account genotype and family history of medullary thyroid carcinoma (MTC) disease aggressiveness. We sought to determine if an association exists independent of genotype, which could provide important information for counseling MEN2A patients in management of their MTC. Pedigrees of patients with ≥5 family members with MEN2A were retrospectively reviewed. Analysis was performed among kindreds with the most frequently observed codon mutation (RET 634). Familial MTC disease aggressiveness was evaluated using: (1) mean age at diagnosis of MTC, (2) current mean age of carriers without MTC, (3) proportion of kindred with MTC with metastatic disease at diagnosis, (4) proportion of kindred with MTC with metastasis/death from MTC as worst outcome, and (5) proportion of kindred with disease progression. 170 affected patients from 12 different MEN2A kindreds met inclusion criteria. The number of affected family members available for study per kindred ranged from 8 to 43 individuals. A difference in mean age of MTC diagnosis was found in screened patients (p = 0.01); mean age of MTC-free patients did not differ (p = 0.93). No differences were noted among kindreds in disease stage at presentation, worst outcome, or progression; marked variation in these measures was noted within families. In conclusion, a difference in age of MTC diagnosis among different RET 634 kindreds was identified. In contrast, notable intra-familial variability in disease aggressiveness was observed. Based on these findings, we recommend counseling patients with codon 634 mutations that their MTC disease course cannot be predicted by that of their relatives.     

Complicating “the good result”: narratives of colorectal cancer screening when cancer is not found

Objectives: In this paper, we analyze narratives from a Photovoice project on colorectal cancer screening that was carried out with people who had undergone screening and were found to not have cancer.

Methods: Three groups, totaling eighteen participants, took part in the project, meeting multiple times over the course of approximately 10 weeks, and discussing photos they took about colorectal cancer screening.

Results: A common way in which the participants conveyed their screening experiences was through reflection on their own or other people's illnesses. Our findings highlight the multiple meanings of receiving a “good” or noncancerous screening result after undergoing cancer screening.

Conclusion: Such findings suggest that framing noncancerous results only in terms of relief or other positive emotions may ignore the realities people and their families face and their remaining concerns. This paper has broader implications for policies to reduce cancer disparities as well as public health and patient-provider communication about screening.     

Stool test for colorectal cancer screening: what is going on?

Given the increasing incidence of colorectal cancer (CRC), performing new and cost-effective stool tests is of particular importance for early diagnosis and treatment. In the present review, we describe the main characteristics, and the performance of the most recently developed stool tests in the screening setting of colorectal tumoral diseases. Most of the studies reported high sensitivity both for adenomas and CRC diagnosis; less than half studies reported also high specificity with respect to stage and localization of the tumor. However, the performance of every single test was extremely variable, reaching >95% specificity for most of DNA-based markers, although lacking sensitivity even in case of invasive CRC. A new potential stool marker of colon cancer is clusterin, a protein of particular interest for its high sensitivity and positive predictive value in patients with highly aggressive CRC.     

Characteristics and screening history of women diagnosed with cervical cancer aged 20–29 years

Background:

There was concern that failure to screen women aged 20–24 years would increase the number of cancers or advanced cancers in women aged 20–29 years. We describe the characteristics of women diagnosed with cervical cancer in England aged 20–29 years and examine the association between the period of diagnosis, screening history and FIGO stage.

Methods:

We used data on 1800 women diagnosed with cervical cancer between April 2007 and March 2012 at age 20–29 from the National Audit of Invasive Cervical Cancers.

Results:

The majority of cancers (995, or 62% of those with known stage) were stage 1A. Cancer at age 20–24 years was rare (12% of those aged 20–29 years), when compared with age 25 (24%) and age 26–29 years (63%); however, cancers in women aged 20–24 years tended to be more advanced and were more often of a rare histological type. For 59% of women under age 30, the cervical cancer was screen detected, most of them (61%) as a result of their first screening test. A three-fold increase in the number of cancers diagnosed at age 25 years was seen since the start of the study period.

Conclusion:

Cervical cancer at age 20–24 years is rare. Most cancers in women under age 30 years are screen detected as microinvasive cancer.     

Family history of cancer and the risk of cancer: a network of case–control studies

BackgroundThe risk of many cancers is higher in subjects with a family history (FH) of cancer at a concordant site. However, few studies investigated FH of cancer at discordant sites.Patients and methodsThis study is based on a network of Italian and Swiss case–control studies on 13 cancer sites conducted between 1991 and 2009, and including more than 12 000 cases and 11 000 controls. We collected information on history of any cancer in first degree relatives, and age at diagnosis. Odds ratios (ORs) for FH were calculated by multiple logistic regression models, adjusted for major confounding factors.ResultsAll sites showed an excess risk in relation to FH of cancer at the same site. Increased risks were also found for oral and pharyngeal cancer and FH of laryngeal cancer (OR = 3.3), esophageal cancer and FH of oral and pharyngeal cancer (OR = 4.1), breast cancer and FH of colorectal cancer (OR = 1.5) and of hemolymphopoietic cancers (OR = 1.7), ovarian cancer and FH of breast cancer (OR = 2.3), and prostate cancer and FH of bladder cancer (OR = 3.4). For most cancer sites, the association with FH was stronger when the proband was affected at age <60 years.ConclusionsOur results point to several potential cancer syndromes that appear among close relatives and may indicate the presence of genetic factors influencing multiple cancer sites.     

Does family history of prostate cancer affect outcomes following radiotherapy?

Objective

To examine family history (FH) as a prognostic factor following radiotherapy (RT).

Materials and methods

Between 1989 and 2007, 1711 men with clinically localized prostate cancer and complete family history who had received RT (median RT dose = 74 Gy) without androgen deprivation therapy were analyzed. FH was defined as any prostate cancer in a first degree relative. For the biochemical failure (BF) outcome, this sample size has 85% power to detect a hazard ratio of 1.56 for positive versus negative FH.

Results

With a median follow-up of 71 months, there was no significant difference in the distribution of Gleason score (GS) or prostate specific antigen (PSA) based on FH. A positive FH was not an independent predictor of BF, distant metastasis (DM), prostate cancer specific mortality (PCSM), or overall mortality (OM) in Cox proportional multivariable analysis. On further analysis in a Cox proportional multivariable analysis, men with two or more first degree relatives with prostate cancer had a significantly higher likelihood of BF and DM than those with no FH, although there was no difference in PCSM or OM. Men with a positive FH (23%) were more likely to be younger, have a lower PSA, and non-palpable disease. There was no interaction between a positive FH and neither race nor treatment era (pre-PSA vs. PSA era).

Conclusions

A positive FH is not a prognostic factor following RT and should not alter standard treatment recommendations. Patients with two or more first degree relatives with prostate cancer had a higher likelihood of BF and DM, but there was no effect on survival. There was no interaction between a positive FH and African American race or treatment era. A positive FH was however, associated with more favorable PSA values and T-stage that may be the result of earlier screening.     

Reliability of cancer family history reported by parents in a case–control study of childhood leukemia

Purpose

To investigate the reliability of family history of cancer reported by parents of children with acute lymphoblastic leukemia (ALL) and parents of healthy control children.

Methods

A total of 301 parents were selected based on positive or negative family history of cancer at baseline, case–control status, and gender of the respondent (mother or father). Baseline responses were compared with responses at the second interview using the same questionnaire. Reliability was measured using proportion of overall agreement, Cohen’s kappa, and Cronbach’s alpha; a logistic regression model was also used to assess the role of the case–control status on overall agreement as the dependent variable.

Results

The overall agreement between interviews was high and similar for cases (85?%) and controls (86?%); there were no consistent effects of respondent gender, age at first interview, or time elapsed between interviews on agreement measures. Agreement measures did not materially vary according to whether respondents were reporting about their mothers, fathers, or siblings.

Conclusions

The study showed very good reliability of reporting family history among young parents of children affected with leukemia and parents of healthy control children.