Implementation of Screening Colonoscopy amongst First-Degree Relatives of Patients with Colorectal Cancer in Turkey : a Cross-Sectional Questionnaire Based Survey

Colorectal cancer (CRC) is the second most common cancer following prostate cancer in men and breast cancer in women with worldwide age-standardized incidence rate of 20.1 per 100,000 in men and 14.6 per 100,000 in women depending on the development levels of the countries (Parkin et al., 2002). According to 2007-2008 Cancer Registry Data published by the Ministry of Health in Turkey, CRC was determined to be the third most common cancer in females with prevalence of 7.8% and fourth most common cancer in males with prevalence of 7.5% (Turkish Ministry of Health Public Health Institute, 2008). Approximately 20% to 25% of cases of CRCs occur in patients with a family history of CRC (Johns and Houlston, 2001), while first-degree relatives (FDRs) are at increased risk of CRC with an associated relative risk


Introduction
Colorectal cancer (CRC) is the second most common cancer following prostate cancer in men and breast cancer in women with worldwide age-standardized incidence rate of 20.1 per 100,000 in men and 14.6 per 100,000 in women depending on the development levels of the countries (Parkin et al., 2002).According to 2007-2008 Cancer Registry Data published by the Ministry of Health in Turkey, CRC was determined to be the third most common cancer in females with prevalence of 7.8% and fourth most common cancer in males with prevalence of 7.5% (Turkish Ministry of Health Public Health Institute, 2008).
Approximately 20% to 25% of cases of CRCs occur in patients with a family history of CRC (Johns and Houlston, 2001), while first-degree relatives (FDRs) are at increased risk of CRC with an associated relative risk of 2.24 (Butterworth et al., 2006).
The characteristic pathophysiology of CRC that involves a slow, latent progression from the first appearance of an adenomatous polyp to the development of CRC has made colonoscopy an ideal screening tool to fight CRC (Muto et al., 1975;Murakami et al., 1990).Offering early detection and colonoscopic excision of precancerous polyps before they transform to CRC (Murakami et al., 1990;Winawer et al., 1993;Bronner et al., 2013), screening colonoscopy has been associated with a substantial decrease in the incidence (Winawer et al., 1993) and mortality rate (Kahi et al., 2009) of CRC in average-risk individuals and FDRs of CRC cases (Lieberman, 1995).
Accordingly, FDRs (parent, sibling or child) of patients with CRC or adenomatous polyps are advised to have screening colonoscopy according to current guidelines which state that screening procedures should start at age 40 years or 10 years younger than the earliest diagnosis in their family, whichever comes first (Winawer et al., 2003;Schmiegel et al., 2004).
However, besides lack of a consensus regarding screening guidelines across organizations, poor adherence to recommendations in guidelines concerning screening colonoscopy in high-risk people has been suggested (Sewitch et al., 2007;Ingrand et al., 2009), as well as low participation of FDRs of CRC patients in the procedure that ranges from 30% to 64% (Bleiker et al., 2005;Denis et al., 2007;Ingrand et al., 2009).
Therefore, the present cross-sectional questionnaire based survey was designed to evaluate the implementation of screening colonoscopy amongst the FDRs of patients with CRC in Turkey.

Study population
A total of 400 FDRs (mean(SD)age: 42.5(12.7)years, 55.5% were females) of 136 patients diagnosed with stage International Union Against Cancer (UICC) I-III CRC during their admission to Antalya Training and Research Hospital (n=88, 64.7%) and Ankara Guven Hospital (n=48, 35.3%) were included in this crosssectional questionnaire-survey based on their voluntary participation.
Written informed consent was obtained from each subject following a detailed explanation of the objectives and protocol of the study which was conducted in accordance with the ethical principles stated in the "Declaration of Helsinki" and approved by the institutional ethics committee.

Study parameters
Data on demographic characteristics, localization of CRC and family history for malignancy were collected in patients with CRC based on medical records.Demographic characteristics, relationship to patient and family history for malignancy other than the index case were evaluated in the FDRs of CRC patients with application of a standardized questionnaire form via face to face method.FDRs were also questioned considering screening colonoscopy including collection of data on the knowledge about screening colonoscopy, source of information, rate of recommendation and application of the procedure along with findings in applied cases as well as the risk for Lynch syndrome related cancer.
Additionally, the rates of having knowledge about screening colonoscopy and receiving screening colonoscopy recommendation were compared with respect to hospital type and the risk for Lynch syndrome related cancer as evaluated in accordance with revised Bethesda criteria (Lynch et al., 2007) in the first degree relatives.

Statistical analysis
Statistical analysis was made using STATA version 10.0.Chi-square (χ 2 ) test or Fischer's exact test were used for the comparison of categorical data.Numerical data were analyzed was using Students' t test for variables with normal distribution, while Mann-Whitney U test was used for non-normally distributed variables.Data were expressed as "mean (standard deviation; SD)", minimummaximum and percent (%) where appropriate.p<0.05 was considered statistically significant.

Characteristics of patients diagnosed with CRC
The mean(SD) age at diagnosis of CRC in the index patients (n=136, 64.0% were males) was 60.1(14.0)years.Rectum (30.9%) was the most common tumor localization and family history for malignancy was positive in 31.6% for more than one type of malignancy in 12.5% and CRC in 10.3% (Table 1).

Characteristics of FDRs of patients with colon carcinoma
Mean(SD) age of first degree relatives (55.5% were males) was 42.5(12.7)years and 68.5% were children of patients with CRC.Family history for malignancy except for the index case was positive in 16.0% of FDRs for more than one type of malignancy in 2.3% and CRC in 5.3% (Table 2).

Data on screening colonoscopy in FDRs of patients
Overall 36.3% (n=145) of FDRs of patients with CRC were determined to have knowledge about colonoscopy.Physicians (66.9%), mostly from general surgery (46.4%) and gastroenterology (38.1%) disciplines were the major source of information.Screening colonoscopy was recommended to 19.5% (n=78) of patient relatives, by a surgeon in 60.3% and by a gastroenterologist in 32.1%, while 48.7% (n=38) of these individuals participated in colonoscopy procedures, mostly (57.9%) one year after the index diagnosis.Screening colonoscopy revealed normal findings in 25 of 38 (65.8%) cases, while precancerous  4).
When compared to individuals without a risk, having a risk for Lynch syndrome related cancer was associated with higher likelihood of having knowledge about screening colonoscopy (55.3 vs 31.8%,p<0.001) and receiving a screening colonoscopy recommendation (46.1 vs 13.3%, p<0.001) among FDRs of patients with CRC (Table 4).

Discussion
This cross-sectional questionnaire based survey on the implementation of screening colonoscopy amongst FDRs of patients with CRC in Turkey revealed that 19.5% of FDRs of patients had received a screening colonoscopy recommendation, while only 48.7% of them had participated in the recommended colonoscopy procedures, mostly (57.9%) one year after the diagnosis of index case.Screening colonoscopy revealed normal findings in 65.8%, while a precancerous lesion was detected in 26.3% of screened FDRs of CRC patients.
Despite the evidence supporting reductions in morbidity and mortality related to CRC in average-risk individuals who aged ≥50 years (Nadel et al., 2002;Levenson, 2003;Sewitch et al., 2007), underutilization of CRC screening has been consistently reported in several studies, at rates ranging from 18% to 34% (Bronner et al., 2013).Along with poor adherence to recommendations in guidelines on screening colonoscopy in high-risk people (Ingrand et al., 2009), it has also been suggested that FDRs of CRC patients are likely to disregard recommendations with participation rates ranging from 30% to 64% (Bleiker et al., 2005;Denis et al., 2007;Ingrand et al., 2009).
Accordingly, in our study population, less than 20% of FDRs of CRC patients were determined to receive screening colonoscopy recommendation and less than 50% to participate in screening procedure which is in agreement with the statement that the screening process has only been performed in a minority of people, with a documented elevated risk for CRC (Ruthotto et al., 2007).lesion was detected in 26.3% of screened individuals.In 19.0% of FDRs of patients, there was a detected risk for Lynch syndrome related cancer and further genetic investigation for microsatellite instability was recommended to these individuals (Table 3).
The low rates of offering colorectal cancer screening to FDRs of CRC patients in the present study seems notable given the consistently reported failure of patients to follow the health care provider's advice leading remarkably low uptake rates even if the high proportion of patients have been advised appropriately (Yusoff et al., 2012).
In a past study on FDRs of patients with CRC, it was reported that screening colonoscopies were performed only in 32% of parents (60.1% before the index case, 39.9% after the index case) and in 39% of siblings (31.7% before the index case, 68.3% after the index case) (Ruthotto et al., 2007).Data from a past study conducted with 1534 FDRs (1381 siblings and 153parents) of 406 patients with CRC in revealed that the frequency of screening colonoscopy in parents and siblings of the index patients was 9% and 20% after the diagnosis of CRC in the index patient, respectively, while 38% of the patients was aware of the increased risk for their FDRs (Kilickap et al., 2012).
In our study population, 68.5% of individuals were children of CRC patients, while 30.0%were their siblings.Compliance rate to procedure in our study was slightly higher to include 48.7% of cases eligible for colonoscopy, with application of screening colonoscopy more commonly after (78.9%; after one year in 57.9%) than before (18.4%) the index diagnosis.
A recent family cancer event was indicated as the most common motivator for a FDR to visit a general practitioner (Al-Habsi et al., 2008;Lim et al., 2011), while an increase in the likelihood of having a discussion about family history with a health professional was documented in parallel to the increase in the perceived risk (Honda and Neugut, 2004).Accordingly, higher likelihood of having knowledge about screening colonoscopy and receiving a screening colonoscopy recommendation among FDRs of CRC patients registered at private than research and training hospitals and also among FDRs with than without a risk for Lynch syndrome related cancer in our study population seems to emphasize the pivotal role of a more favorable patient-physician communication as well as the presence and awareness of high risk status in FDRs in better adherence to international guidelines on screening colonoscopy for FDRs of CRC patients.
Detecting precancerous polyps has been associated with a significant reduction in mortality given that the most important part of colorectal neoplasia is derived from polyps (Rex et al., 2000).In this respect, our finding related to identification of a precancerous lesion in 26.3% FDRs who were screened as recommended seems consistent with the well-known increased risk of developing CRC and the range of (6.7-13.3%) of advanced colorectal neoplasia in FDRs of patients with CRC (Ruthotto et al., 2007;Sewitch et al., 2007;Armelo et al., 2011).
While reaching out to FDRs to be able inform them about their level of risk and the corresponding screening recommendations is an integral part of the medical protocol, there is no standardized systematic mechanism for providing information about the risk for family members of the index case (Bronner et al., 2013;Cameron et al., 2013).Notably, in a past study on physician views on screening colonoscopy in FDRs of CRC patients, participated general practitioners were reported to identify that someone other than themselves was better placed to give the information, while gastroenterologist and surgeons preferred the transfer of educational information materials by index patients themselves to their relatives and the latter to their general practitioners (Ingrand et al., 2009).
In this regard, it should be emphasized that consistent with the statement that doctor endorsement is a key factor in promoting screening participation (Lim et al., 2011;Cameron et al., 2013), physicians were the major source of information (66.9%) identified by FDRs of CRC patients in our study population, while general surgeons (46.4%) and gastroenterologists (38.1%) were the principal information providers rather than the family medicine specialists (1.0%).
Unfortunately, it has been documented that ranging from 30% to 69% according to studies, most of the physicians were not aware of the low rates of participation in colonoscopy screening (Longacre et al., 2006;Ingrand et al., 2009) and they were convinced that the great majority of FDRs get themselves screened (Ingrand et al., 2009).Based on the statement that being asked by a health professional about their family history of CRC was a significant predictor of being screened in accordance to guidelines among FDRs (Courtney et al., 2013), it seems necessary to raise awareness of physicians involved in the care of CRC patients about the actual compliance rate of FDRs for screening colonoscopy besides their predominant role as physicians in motivating their patients to participate in screening through their advice and recommendations (Ingrand et al., 2009).
Lack of symptoms related to colon disease has been indicated amongst the most common reasons for low screening colonoscopy rates (Chong et al., 2013), while data from a multicentre questionnaire study in the Asia Pacific regions revealed lesser likelihood of undergoing colonoscopy screening if patients were well and perceived low risk (Koo et al., 2012).
Notably, consistent with the clear evidence for suboptimal adherence to colonoscopy screening among FDRs of CRC patients, an acknowledged high-risk population (Bronner et al., 2013), participation to screening colonoscopy was noted only in 48.7% of FDRs who received a screening colonoscopy recommendation in the present study.Hence, aside from physician's proper adherence to guidelines in terms of recommending screening colonoscopy, patient adherence to participate colonoscopy seems also considerably important in early detection of CRC among FDRs of an index case.
Supporting the demonstration of factors such as knowledge about CRC, a positive attitude toward screening, and physician recommendation amongst the possible predictors for CRC-screening participation in published studies (Ioannou et al., 2003;Ruthotto et al., 2007;Bronner et al., 2013), only 36.3% of FDRs in our study population identified that they had knowledge about screening colonoscopy.Besides, participation in screening colonoscopy after diagnosis in the index patients was reported to be significantly higher in those families where the index patients knew about the increased risk for CRC DOI:http://dx.doi.org/10.7314/APJCP.2014.15.14.5523Screening Colonoscopy by First-Degree Relatives of CRC Cases in Turkey in their families (Ruthotto et al., 2007).
In a past study concerning the risk factors and the health beliefs of Turkish people aged over 50 years regarding colorectal cancer screening, participation rates to colorectal cancer screening programs were reported to be low (11.3%)mostly due to lack of knowledge (81.3%) which was considered as the most important barrier for involvement in CRC screening programs (Tastan et al., 2013).
In a past study concerning the physician cognition to follow CRC screening guidelines in relation to main barriers in the clinical practice, overall poor cognition of CRC screening guidelines for high-risk populations was reported across all practitioners, even among gastroenterologists and oncologists despite their substantial role in the management of CRC (Chen et al., 2013).
Accordingly, by supporting establishment of family cancer registries (Vasen, 2008) along with implementation of training programs for raising awareness among physicians about adherence to guidelines on screening colonoscopy and CRC patients and their FDRs about the risk for CRC could translate into an increase in adherence rates to screening colonoscopy (Lieberman et al., 1995;Bronner et al., 2013).
Certain limitations to this study should be considered.First, the cross-sectional design limits causal inferences.Second, small sample size and potential for self-selection bias are inherent in qualitative methods and should be considered before generalizing the application of our findings in daily practice.
In conclusion, the findings from this cross-sectional questionnaire based survey on the implementation of screening colonoscopy amongst FDRs of patients with CRC in Turkey revealed less than 20% of FDRs of patients had received a screening colonoscopy recommendation, only 46.7% participated in the procedure with detection of precancerous lesion in 26.3%.Emphasizing the integral role of patient-physician communication and awareness of high-risk status in implementation of screening colonoscopy, FDRs of CRC patients from a private than a training-research hospital along with FDRs with than without a risk for Lynch syndrome related cancer were more likely to have knowledge about screening colonoscopy and to receive a screening colonoscopy recommendation.Our findings seem to indicate that rise of awareness about screening colonoscopy amongst patients with CRC and their FDRs and motivation of physicians for targeted screening would improve the participation rate in screening colonoscopy by FDRS of patients with CRC.

Table 4 . Data on Screening Colonoscopy in First Degree Relatives of Patients with Respect to Hospital type and Lynch Syndrome
*Data were shown as n(%)