Family history of colorectal cancer and prevalence of advanced colorectal neoplasia in asymptomatic screened populations in different age groups
Journal Pre-proof Family history of colorectal cancer and prevalence of advanced colorectal neoplasia in asymptomatic screened populations in differen...
Journal Pre-proof Family history of colorectal cancer and prevalence of advanced colorectal neoplasia in asymptomatic screened populations in different age groups Masau Sekiguchi, MD, PhD, Yasuo Kakugawa, MD, Keiko Nakamura, MD, PhD, Minori Matsumoto, MD, Yutaka Tomizawa, MD, MSc, Yoshitaka Murakami, PhD, Yutaka Saito, MD, PhD, Takahisa Matsuda, MD, PhD. PII:
S0016-5107(20)30091-2
DOI:
https://doi.org/10.1016/j.gie.2020.01.033
Reference:
YMGE 11949
To appear in:
Gastrointestinal Endoscopy
Received Date: 14 November 2019 Accepted Date: 16 January 2020
1. Cancer Screening Center, National Cancer Center Hospital, Tokyo, Japan 2. Division of Screening Technology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan 3. Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan 4. Division of Gastroenterology, Harborview Medical Center, University of Washington, Seattle, Washington, USA 5. Department of Medical Statistics, Toho University, Tokyo, Japan
Correspondence to: Masau Sekiguchi, MD, PhD Cancer Screening Center, National Cancer Center Hospital 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
Short title: family history and colorectal neoplasia
Key words: Advanced colorectal neoplasia; colorectal cancer; colorectal cancer screening; family history; first-degree relative
Conflicts of interest: The authors have no conflict of interest.
Author contributions: Masau Sekiguchi and Takahisa Matsuda designed the study and collected and analyzed the data. All authors contributed to the interpretation of the data. Masau Sekiguchi drafted the article. Yasuo Kakugawa, Keiko Nakamura, Minori Matsumoto, Yutaka Tomizawa, Yoshitaka Murakami, Yutaka Saito, and Takahisa Matsuda contributed to the critical revision of the article for important intellectual content. All authors approved the final version of the article.
Acknowledgments: The authors thank H. Nikki March, PhD and Angela Morben, DVM,
ELS
from
Edanz
Group
(www.edanzediting.com/ac)
and
Editage
(www.editage.com) for editing a draft of this manuscript. The present study was supported by JSPS KAKENHI (grant number 17K15978) and the National Cancer Center Research and Development Fund (30-A-16).
Family history of colorectal cancer and prevalence of advanced colorectal neoplasia in asymptomatic screened populations in different age groups
Background and Aims: The clinical significance of a family history (FH) of colorectal cancer (CRC) in first-degree relatives (FDRs) in CRC screening stratified by different age groups of screened individuals is not fully understood. We investigated the relationship between FH and the presence of advanced colorectal neoplasia (ACN) in screened individuals in different age groups. Methods: Data from screened individuals aged 40 to 54 years (n=2,263) and 55 to 69 years (n=2,621) who underwent their first-ever screening colonoscopy were analyzed. The relationship between FH and ACN was examined, and a multivariate logistic regression analysis incorporating other baseline characteristics was performed. Results: Among individuals aged 40 to 54 years, the prevalence of ACN was significantly higher in 249 individuals with affected FDRs than in those without (5.6% vs 1.6%; P<0.01), with an adjusted OR of 3.7 (95% confidence interval, 1.9–7.0; P<0.01), and the prevalence was particularly high in those having FDRs with CRC mortality (7.3%). Among individuals aged 55 to 69 years, the prevalence of ACN was not significantly different between 291 individuals with affected FDRs and those 1
without (5.8% vs 5.8%; P=0.95); however, individuals with 2 FDRs with CRC affection and mortality showed a high prevalence of ACN (17.4% and 42.9%, respectively). Conclusions: An FH of CRC in FDRs was associated with a higher prevalence of ACN in younger individuals with a particularly high impact of the FH of CRC mortality. In contrast, the impact of FH was weaker in older individuals except those having 2 FDRs with CRC affection or mortality.
INTRODUCTION Colorectal cancer (CRC) screening is conducted in many countries to lower the mortality of CRC.1 Various guidelines and recommendations for CRC screening are available from multiple organizations, and many guidelines consider individuals with a family history (FH) of CRC in first-degree relatives (FDRs) as a high-risk group requiring intensive screening.2-6 An FH of CRC in FDRs (excluding known hereditary CRC) is reportedly associated with a higher risk of colorectal neoplasia, and intensive screening is recommended for those with an FH of CRC.2-15 Given the lack of consensus about the association between the age of screened individuals and the influence of an FH of CRC as a risk factor for colorectal neoplasia, the age of screened individuals is not currently incorporated into the CRC screening recommendations for those with an FH of CRC.2-6 Therefore, intensive interventions are 2
generally recommended for those with a positive FH regardless of their age, and intensive interventions may continue to be conducted excessively even for individuals of advanced age.2-6 In this context, the association of age and the influence of FH should be examined further to establish more appropriate screening for those with a positive FH according to their age. Several previous studies, including a recent meta-analysis, have suggested that the influence of an FH of CRC in FDRs as a risk factor for colorectal neoplasia weakens as the age of screened individuals increases.7,8,14 Schoen et al16 evaluated the influence of FH on the risk of CRC incidence and mortality based on the analysis of a large number of individuals participating in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial, and the authors found that individuals aged ≥55 years with one CRC-affected FDR showed only a modest increase in the risk of CRC. Among these previous studies, however, limited studies included detailed information of FH, data from high-quality colonoscopy, and sufficient consideration of confounding factors. As a result, a high level of heterogeneity was observed in the recent meta-analysis.14 Additionally, some reports contradict the finding of a weakening influence of FH in the older population.17,18 In the present study, we examined the relationship between an FH of CRC in FDRs and the presence of advanced colorectal neoplasia (ACN) in asymptomatic
3
screened individuals aged 40 to 54 and 55 to 69 years to determine whether the influence of FH as a risk factor for ACN weakens in older individuals. For the accurate assessment of the relationship, we explored data from high-quality colonoscopy examinations and detailed FH information, with sufficient consideration of potentially confounding factors.
METHODS Study setting and design This study was approved by the Ethics Committee for Clinical Research of the National Cancer Center (NCC) in Tokyo, Japan. The study was conducted using the database of screened individuals at the Cancer Screening Center of the NCC in Tokyo, Japan. The Cancer Screening Center was founded in February 2004 to prospectively evaluate cancer screening programs.19,20 Since then, opportunistic cancer screening has been provided for asymptomatic average-risk individuals; total colonoscopy is mainly used as a primary screening tool for CRC. Screening results have been prospectively accumulated in the database at the Cancer Screening Center. The data of screened individuals aged 40 to 69 years who underwent their first-time screening total colonoscopy at the Cancer Screening Center from February
4
2004 to March 2013 were retrospectively analyzed in this study. Permission for the use of data was obtained from screened individuals involved in this study. During this period, detailed information on an FH of CRC in FDRs was surveyed for each screened individual using a self-administered questionnaire. Their lifestyles, demographic characteristics, and medical history were also surveyed at their first screening.19,20 Hence, the data of that period were used for this study. The age range of 40 to 69 years was selected because it is the main target age for CRC screening, including screening for average-risk populations and intensive screening for potentially high-risk populations with a positive FH.2-6 The data of individuals who met the following criteria were excluded from the present analysis: (1) Data from the self-administered questionnaire were unavailable. (2) The screening colonoscopy procedure was incomplete because of failure to reach the cecum and/or poor bowel preparation. From the above-mentioned database, data on an FH of CRC in FDRs, other baseline characteristics of screened individuals, and colorectal neoplasia detected at the screening colonoscopy were extracted, and the relationship between FH and the presence of ACN was then evaluated.
Colonoscopy procedure and evaluation of ACN
5
ACN was detected and diagnosed endoscopically at the time of screening colonoscopy, and the final diagnoses were confirmed based on pathological evaluation.19,20 ACN consisted of CRC (with invasion beyond the muscularis mucosa) and advanced adenoma (AA; defined as an adenoma with a diameter of ≥10 mm, high-grade dysplasia, or villous histology of ≥25%).21-23 Lesions that were diagnosed as “intramucosal carcinoma” in Japan were classified as advanced adenoma with high-grade dysplasia in this study. All colonoscopy procedures were performed with standard video endoscopic equipment with narrow-band imaging and magnification functions (CF-H260AZI, PCF-Q240ZI; Olympus Corp, Tokyo, Japan).19,20 Colorectal lesions were evaluated under magnification with image-enhanced endoscopy (chromoendoscopy [0.4% indigo carmine dye spraying and, if necessary, 0.05% crystal violet staining] and/or narrow-band imaging). All endoscopists were board-certified by the Japanese Gastrointestinal Endoscopy Society and highly experienced with extensive knowledge in endoscopic diagnosis using magnifying image-enhanced endoscopy.19,20 Bowel cleansing was performed using polyethylene glycol or magnesium citrate, and the Aronchick Scale was used to assess the quality of bowel cleansing; a score of 4 or 5 was judged as poor bowel preparation.19,20,24
6
Evaluation of FH of CRC and other baseline characteristics of screened individuals The following factors of an FH of CRC in FDRs of each screened individual were extracted and evaluated: the presence of CRC in FDRs, FDRs who died of CRC, and FDRs with CRC diagnosed at <50 and <60 years, and the number and type (parent, full sibling, or child) of affected FDRs. The following baseline characteristics that were potentially related to ACN were also extracted and evaluated: age, sex, body mass index, presence of diabetes mellitus, and status of smoking, alcohol drinking, and regular intake of nonsteroidal anti-inflammatory drugs.19,25,26
Statistical analysis The baseline characteristics were assessed and compared between individuals with and without a positive FH using the Mann–Whitney U test for continuous variables and the chi-square test for categorical variables. The characteristics of ACN in individuals with and without a positive FH were assessed in the same way. The relationships between the presence of ACN (CRC and AA) and the aforementioned
7
factors of an FH of CRC were examined by univariate analyses using the chi-square test. A multivariate logistic regression of CRC-affected FDRs and other clinical factors (age, sex, and status of smoking, drinking, and nonsteroidal anti-inflammatory use) was performed to estimate the adjusted odds ratio (OR) of an FH for ACN. All data analyses were performed using SPSS software, version 24.0 (IBM Corp, Armonk, NY, USA).
RESULTS Baseline characteristics of screened individuals aged 40 to 54 and 55 to 69 years A flowchart of the data used in this study is shown in Figure 1. The data of 4,884 asymptomatic screened individuals were used. None of these individuals had inflammatory bowel disease, a history of bowel resection, or an FH of hereditary CRC. Of 2,263 screened individuals aged 40 to 54 years, 249 (11.0%) had FDRs with CRC. No significant difference in the baseline characteristics was observed between these 249 individuals with affected FDRs and the remaining 2,014 individuals without affected FDRs (Table 1). Among the 2,621 screened individuals aged 55 to 69 years, 291 (11.1%) had FDRs with CRC. Similar to the individuals aged 40 to 54 years, there were no significant differences in the baseline characteristics between these 291 individuals and the other 2,330 individuals without affected FDRs (Table 2). 8
Relationship between FH of CRC in FDRs and presence of ACN in individuals aged 40 to 54 years Among 2,263 individuals aged 40 to 54 years, 47 had ACN, including 6 with CRC. The relationship between an FH of CRC in FDRs and the presence of ACN in that population is summarized in Table 1. The prevalence of ACN was significantly higher among individuals with than without affected FDRs (5.6% vs 1.6%; P<0.01). The prevalence of ACN was also higher in individuals with FDRs who had died of CRC, those with CRC-affected parent(s), and those with CRC-affected sibling(s). No statistically significant association was observed between the presence of ACN and the presence of younger affected FDRs (<50 and <60 years). The OR of the presence of affected FDRs for ACN, which was adjusted by all other baseline characteristics, were 3.7 (95% confidence interval [CI], 1.9–7.0; P<0.01). The relationships between the FH and the presence of AA and CRC are also summarized in Table 3. A significantly higher prevalence of AA was observed among individuals with affected FDRs, affected parent(s), and FDRs who had died of CRC. The prevalence of CRC had a significant relationship with the presence of CRC-affected
9
sibling(s) and FDRs with CRC diagnosed at the age of <60 years.
Relationship between FH of CRC in FDRs and presence of ACN in individuals aged 55 to 69 years Among 2,621 individuals aged 55 to 69 years, 151 had ACN, including 15 with CRC. The association between FH and the presence of ACN in these individuals is shown in Table 4. The prevalence of ACN was not significantly different between these 291 individuals with affected FDRs and the other 2,330 individuals without affected FDRs (5.8% vs 5.8%, respectively; P=0.95). There were also no statistically significant relationships between the presence of ACN and the presence of each affected FDR (parent/sibling/child), FDRs who had died of CRC, or younger affected FDRs (<50 and <60 years). Despite this lack of significant associations, individuals with 2 affected FDRs or 2 FDRs with CRC mortality showed a significantly higher prevalence of ACN than the others. The adjusted OR of the presence of affected FDRs for ACN was 1.0 (95% CI, 0.6–1.7; P=0.92). Table 4 also summarizes the relationships between the FH and the presence of AA and CRC. No statistically significant difference was observed in the prevalence of AA between individuals with and without affected FDRs. Only those with 2 FDRs who
10
had died of CRC showed a significantly higher prevalence of AA. The prevalence of CRC was significantly related with the presence of FDRs who had died of CRC, 2 affected FDRs, and FDRs with CRC diagnosed at the age of <50 years.
Characteristics of detected ACN in individuals with and without affected FDRs in both age groups The characteristics of detected ACNs in screened individuals with and without affected FDRs in both age groups are summarized in Table 5. No statistically significant difference was observed between individuals with and without affected FDRs in both age groups with respect to the number of ACN per individual, lesion type, size, location, and macroscopic type.
Prevalence of ACN in screened individuals with/without affected FDRs stratified by age of screened individuals The prevalence of ACN according to the presence of affected FDRs and the age category (in 5-year increments) of screened individuals is shown in Table 6, and the adjusted OR of the presence of affected FDRs for ACN in each age category with the 95% CI is shown in Figure 2. The prevalence of ACN in individuals aged 45 to 49 and
11
50 to 54 years was significantly higher in those with than without a positive FH. However, a statistically significant difference in the prevalence of ACN between those with and without affected FDRs was not observed in individuals aged ≥55 years and in those aged 40 to 44 years. The adjusted OR of the presence of affected FDRs for ACN was 4.4 (95% CI, 2.3–8.7; P<0.01) in individuals aged 45 to 54 years.
DISCUSSION The present study demonstrated the clinical significance of an FH of CRC in FDRs as a risk factor for ACN in younger asymptomatic screened individuals aged 40 to 54 years. In contrast, a positive FH had a weaker impact on relatively older screened individuals aged 55 to 69 years except those with 2 affected FDRs. Under the current circumstances in which no consensus has been reached regarding the relationship between the age of screened individuals and the influence of FH, the findings from our high-quality data confirming the weaker impact of the FH with increasing age of screened populations is meaningful for improving CRC screening and management of individuals with a positive FH. However, we acknowledge that the findings of some other studies are not in accordance with our findings; these other studies showed that the impact of FH is higher in relatively older populations (≥60 years).17,18 We believe that this discrepancy can be explained by the following strengths of our study. 12
First, the baseline characteristics of screened populations other than FH were extensively evaluated in this study. As a result, we were able to assess the true impact of FH on ACN adjusted by other potential confounding factors. Even after adjustment using other potentially confounding factors, a significant relationship between an FH of CRC in FDRs and the presence of ACN was demonstrated in younger individuals aged 40 to 54 years, and not in older individuals aged 55 to 69 years. The second strength of this study is the high quality of the colonoscopies performed and the highly reliable data on ACN detection. As described above, all colonoscopic procedures were performed by highly experienced endoscopists. Although the quality measurements of each endoscopist were not evaluated, the high quality was justified by high adenoma detection rates of the initial screening colonoscopies at the Cancer Screening Center of the NCC, Tokyo during the study period as disclosed in our recent reports (36.7% and 44.5% for those aged ≥40 and ≥50 years, respectively).19,20 The third strength of this study is that detailed information on FH was assessed. Notably, as a result of the detailed assessment, an important novel finding on FH was clarified. CRC death in FDRs as a risk factor for ACN was separately assessed in this study, and the higher impact of CRC death in FDRs on ACN than of the presence of CRC-affected FDRs on ACN was demonstrated in the younger population aged 40 to 54
13
years. We assume that the clinical significance of fatal CRC is greater than that of nonfatal CRC when we assess an FH of CRC. The detailed assessment of FH information in individuals aged 55 to 69 years showed that although the presence of affected FDRs was not a risk factor for ACN, the presence of 2 FDRs with CRC and CRC death were risk factors for ACN. In line with the aforementioned higher clinical significance of CRC death in FDRs in the younger population, the presence of 2 FDRs with CRC death had greater clinical significance than the presence of 2 CRC-affected FDRs. With respect to the type and age at the diagnosis of affected FDRs, no distinctive risk factors for ACN were identified in our analyses. This could be partly due to the insufficient number of several subgroups of individuals stratified by conditions of FH and age. Considering the reported potential clinical significance of age at the time of diagnosis of affected FDRs, further evaluation using a larger dataset is warranted.2-6 Similarly, the clinical significance of more than one affected FDRs in younger populations is worth further evaluation in future studies. Our analysis on the relationships between the FH and the prevalence of AA and CRC has provided us further insights. In the younger age group (40–54 years), the FH of FDRs with CRC and CRC-related mortality was significantly associated with higher prevalence of AA. The prevalence of CRC was also numerically higher among those
14
with affected FDRs (0.8%) than among those without (0.2%), despite the lack of statistically significant difference presumably owing to the small number of CRC cases. It is considered that the FH may affect both AA and CRC in this age group (40–54 years). In contrast, in the older age group (55–69 years), only a small numerical difference with no statistically significant difference was observed in the prevalence of AA between individuals with and without affected FDRs (4.8% vs 5.3%). However, despite the lack of statistical difference, the prevalence of CRC was numerically higher among those with affected FDRs than among those without (1.0% vs 0.5%). The FH may be more strongly associated with CRC than with AA in the older age group (55–69 years). A relatively high prevalence of CRC among detected ACN in those aged 55 to 69 years with the FH also supports this idea. This may be explained as follows. After individuals reach a certain age (55 years), AA can more frequently develop even without the FH owing to increasing age and other factors, as supported by the finding that the prevalence of AA in the older age group without the FH (5.3%) reached the prevalence in the younger age group with affected FDRs (5.2%). The potentially higher prevalence of CRC among individuals with the FH in the older age group may be affected by AAs that developed during their younger age and progressed to CRC without any symptoms. Further studies involving more CRC cases are warranted to
15
validate this hypothetical mechanism. Assessment of the prevalence of ACN in screened populations stratified by age categories (in 5-year increments) suggests that young asymptomatic individuals aged 40 to 44 years have a low risk of ACN regardless of FH. However, because of the relatively small number of individuals aged 40 to 44 years with a positive FH, the significance of FH in this age group cannot be ignored and further assessment using a larger dataset is required. After excluding individuals aged 40 to 44 years from the younger population, the adjusted OR of an FH for ACN was high (4.4; 95% CI, 2.3– 8.7) in those aged 45 to 54 years. This result emphasizes the necessity of careful attention to the FH as a strong risk factor for ACN especially among screened individuals aged 45 to 54 years. How to effectively screen CRC in high-risk populations with a positive FH is of critical importance. In younger populations, particularly those aged 45 to 54 years, total colonoscopy as a primary screening tool for those with a positive FH seems a reasonable option. However, considering that the prevalence of ACN in individuals aged 45 to 49 years with a positive FH is still relatively low (5.6%), the burden of providing total colonoscopy as a primary screening tool for all individuals aged 45 to 49 years with a positive FH may be too high. Although CRC screening is clearly necessary
16
for those aged 45 to 49 years with a positive FH, further discussion regarding the optimal screening method for these individuals is warranted. The consideration of an FH of CRC mortality may be useful for recommendation of intensive screening. In relatively older individuals aged 55 to 69 years, although the presence of CRC in FDRs was not detected as a risk factor for ACN, the presence of 2 FDRs with CRC and CRC death was shown to be a risk factor. The prevalence of ACN in individuals aged 55 to 69 years with 2 FDRs with CRC affection and mortality was high (17.4% and 42.9%, respectively). Therefore, although intensive screening is not required for those aged 55 to 69 years with only one affected FDR, individuals with 2 FDRs with CRC or CRC mortality are considered good candidates for screening using colonoscopy as a primary screening tool. This study has several limitations. First, a single-center database was used, which threatens external validity. Second, data after March 2013 were not used in this study because information on an FH of CRC was not available for that period. Third, selection bias from a health-consciousness perspective may have been present. Fourth, in the stratified assessment for the prevalence of ACN according to age and FH, the number of individuals in some subgroups was not sufficiently large. A larger-scale study would be helpful to further validate the prevalence of ACN stratified by various
17
conditions of age and FH. Fifth, the data regarding FH were based on a self-reported questionnaire in this study. However, self-reported FH information has been reported to be accurate in previous studies.27,28 Sixth, information regarding an FH of CRC in second-degree relatives was not examined in this study, and we acknowledge that such an FH may be related to the incidence of colorectal neoplasia.6,9,12,15 However, as previous studies indicated, the impact of a positive FH in FDRs is believed to be higher than that in second-degree relatives. In conclusion, an FH of CRC in FDRs is a significant risk factor for ACN in younger asymptomatic screened individuals, particularly those aged 45 to 54 years. In contrast, FH may have a weaker impact for relatively older screened populations aged 55 to 69 years except those with 2 affected FDRs. In both age groups, the information of CRC mortality in FDRs may also be helpful for considering optimal screening due to its high influence on the prevalence of ACN.
References 1. Schreuders EH, Ruco A, Rabeneck L, et al. Colorectal cancer screening: a global overview of existing programmes. Gut 2015; 64: 1637–1649. 2. US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for Colorectal Cancer: US Preventive Services Task Force 18
Recommendation Statement. JAMA. 2016; 315: 2564–2575. 3. Cairns SR, Scholefield JH, Steele RJ, et al; British Society of Gastroenterology; Association of Coloproctology for Great Britain and Ireland. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut. 2010; 59: 666–689. 4. Sung JJ, Ng SC, Chan FK, et al; Asia Pacific Working Group. An updated Asia Pacific Consensus Recommendations on colorectal cancer screening. Gut. 2015; 64: 121–132. 5. Wolf AMD, Fontham ETH, Church TR, et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin. 2018; 68: 250–281. 6. Leddin D, Lieberman DA, Tse F, et al. Clinical Practice Guideline on Screening for Colorectal Cancer in Individuals With a Family History of Nonhereditary Colorectal Cancer or Adenoma: The Canadian Association of Gastroenterology Banff Consensus. Gastroenterology. 2018; 155: 1325–1347. 7. Fuchs CS, Giovannucci EL, Colditz GA, et al. A prospective study of family history and the risk of colorectal cancer. N Engl J Med. 1994; 331: 1669–1674. 8. Leu M, Reilly M, Czene K. Evaluation of bias in familial risk estimates: a study of
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common cancers using Swedish population-based registers. J Natl Cancer Inst. 2008; 100: 1318–1325. 9. Taylor DP, Burt RW, Williams MS, et al. Population-based family history-specific risks for colorectal cancer: a constellation approach. Gastroenterology. 2010; 138: 877–885. 10. Armelao F, Paternolli C, Franceschini G, et al. Colonoscopic findings in first-degree relatives of patients with colorectal cancer: a population-based screening program. Gastrointest Endosc. 2011; 73: 527–534. 11. Ng SC, Lau JY, Chan FK, et al. Increased risk of advanced neoplasms among asymptomatic siblings of patients with colorectal cancer. Gastroenterology. 2013; 144: 544–550. 12. Samadder NJ, Curtin K, Tuohy TM, et al. Increased risk of colorectal neoplasia among family members of patients with colorectal cancer: a population-based study in Utah. Gastroenterology. 2014; 147: 814–821. 13. Wong MC, Ching JY, Chiu HM, et al. Risk of Colorectal Neoplasia in Individuals With Self-Reported Family History: A Prospective Colonoscopy Study from 16 Asia-Pacific Regions. Am J Gastroenterol. 2016; 111: 1621–1629. 14. Wong MCS, Chan CH, Lin J, et al. Lower Relative Contribution of Positive Family
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History to Colorectal Cancer Risk with Increasing Age: A Systematic Review and Meta-Analysis of 9.28 Million Individuals. Am J Gastroenterol. 2018; 113: 1819– 1827. 15. Tian Y, Kharazmi E, Sundquist K, et al. Familial colorectal cancer risk in half siblings and siblings: nationwide cohort study. BMJ. 2019; 364: l803. 16. Schoen RE, Razzak A, Yu KJ, et al. Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer. Gastroenterology. 2015; 149: 1438–1445. 17. Tsai FC, Strum WB. Impact of a family history of colorectal cancer on the prevalence of advanced neoplasia at colonoscopy in 4,967 asymptomatic patients. Dig Dis Sci. 2012; 57: 3234–3239. 18. Park CH, Kim NH, Park JH, et al. Impact of family history of colorectal cancer on age-specific prevalence of colorectal neoplasia. J Gastroenterol Hepatol. 2019; 34: 537–543. 19. Sekiguchi M, Kakugawa Y, Matsumoto M, et al. A scoring model for predicting advanced colorectal neoplasia in a screened population of asymptomatic Japanese individuals. J Gastroenterol. 2018; 53: 1109–1119. 20. Sekiguchi M, Otake Y, Kakugawa Y, et al. Incidence of Advanced Colorectal
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Neoplasia in Individuals With Untreated Diminutive Colorectal Adenomas Diagnosed by Magnifying Image-Enhanced Endoscopy. Am J Gastroenterol. 2019; 114: 964–973. 21. Lieberman DA, Weiss DG, Bond JH, et al. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. N Engl J Med. 2000; 343: 162–168. 22. Hamiliton SR, Bosman FT, Boffetta P, et al. Carcinoma of the colon and rectum. In: Bosman FT, Carneiro F, Hruban RH, et al, editors. WHO Classification of Tumors of the Digestive System. 4th ed. Lyon: IARC; 2010. p. 134–146. 23. Winawer SJ, Zauber AG. The advanced adenoma as the primary target of screening. Gastrointest Endosc Clin N Am. 2002; 12: 1–9, v. 24. ASGE Standards of Practice Committee, Saltzman JR, et al. Bowel preparation before colonoscopy. Gastrointest Endosc. 2015; 81: 781–794. 25. Cole BF, Logan RF, Halabi S, et al. Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J Natl Cancer Inst. 2009; 101: 256–266. 26. Peng L, Weigl K, Boakye D, et al. Risk Scores for Predicting Advanced Colorectal Neoplasia in the Average-risk Population: A Systematic Review and Meta-analysis.
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Am J Gastroenterol. 2018; 113: 1788–1800. 27. Aitken J, Bain C, Ward M, et al. How accurate is self-reported family history of colorectal cancer? Am J Epidemiol. 1995; 141: 863–871. 28. Murff HJ, Spigel DR, Syngal S. Does this patient have a family history of cancer? An evidence-based analysis of the accuracy of family cancer history. JAMA. 2004; 292: 1480–1489.
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Table 1. Baseline characteristics of screened individuals. Individuals aged 40 to 54 years.
Total
FH (+)
FH (−) P value
Age, years
n=2,263
n=249
n=2,014
47 (44–50)
48 (44–50)
47 (44–51)
Sex
0.752 0.138
Male
1,299 (57.4)
132 (53.0)
1,167 (57.9)
Female
964 (42.6)
117 (47.0)
847 (42.1)
22.6 (20.7–25.0)
22.6 (20.8–25.1)
22.6 (20.7–25.0)
BMI, kg/m2 Smoking
0.582 0.203
Non-smoker
1,159 (51.2)
137 (55.0)
1,022 (50.7)
Current/ past smoker
1,104 (48.8)
112 (45.0)
992 (49.3)
Alcohol
0.602
Non-drinker
356 (15.7)
42 (16.9)
314 (15.6)
Current/ past drinker
1,907 (84.3)
207 (83.1)
1,700 (84.4)
Regular intake of
0.947
NSAIDs Absent
2,244 (99.2)
247 (99.2)
1,997 (99.2)
Present
19 (0.8)
2 (0.8)
17 (0.8)
Diabetes mellitus
0.459
Absent
2,206 (97.5)
241 (96.8)
1,965 (97.6)
Present
57 (2.5)
8 (3.2)
49 (2.4)
24
Table 2.
Baseline characteristics of screened individuals. Individuals aged 55 to
69 years.
Total
FH (+)
FH (−) P value
Age, years
n=2,621
n=291
n=2,330
61 (58–65)
61 (58–64)
61 (58–65)
Sex
0.558 0.740
Male
1,465 (55.9)
160 (55.0)
1,305 (56.0)
Female
1,156 (44.1)
131 (45.0)
1,025 (44.0)
22.9 (21.1–24.8)
23.0 (21.3–25.3)
22.9 (21.0–24.8)
2
BMI, kg/m Smoking
0.08 0.923
Nonsmoker
1,376 (52.5)
152 (52.2)
1,224 (52.5)
Current/ past smoker
1,245 (47.5)
139 (47.8)
1,106 (47.5)
Alcohol
0.881
Non-drinker
684 (26.1)
77 (26.5)
607 (26.1)
Current/ past drinker
1,937 (73.9)
214 (73.5)
1,723 (73.9)
Regular intake of
0.940
NSAIDs Absent
2,524 (96.3)
280 (96.2)
2,244 (96.3)
Present
97 (3.7)
11 (3.8)
86 (3.7)
Diabetes mellitus
0.829
Absent
2,442 (93.2)
272 (93.5)
2,170 (93.1)
Present
179 (6.8)
19 (6.5)
160 (6.9)
Data are presented as median (interquartile range) or n (%). BMI, body mass index; FH, family history; NSAIDs, nonsteroidal anti-inflammatory drugs.
25
Table 3. Relationships between FH of CRC in FDRs and the presence of ACN in screened individuals. Individuals aged 40 to 54 years. ACN Number
OR for
P
Number
OR for
P
Number
OR for
P
number
(proporti
ACN
value
(proporti
AA
value
(proporti
CRC
value
of
on) of
(95%CI)
on) of
(95%CI)
on) of
(95%CI)
individu
individu
individu
individu
als
als with
als with
als with
ACN
AA
CRC
<0.001 14
Absent
CRC
Total
CRC-affected FDRs Present
AA
3.6 (1.9–
<0.001 13
0.080
3.8 (1.9–
4.1 (0.7– 2 (0.8%)
249 (5.6%)
6.8)
(5.2%)
7.4)
33
Referenc
29
Referenc
22.3) Referenc
2014
4 (0.2%) (1.6%)
e
Number of
(1.4%)
e
e
<0.001 <0.001
0.193
CRC-affected FDRs 2
9
1
240
0
0 (0.0%)
–
0 (0.0%)
–
14
3.7 (2.0–
13
3.9 (2.0–
0 (0.0%)
– 4.2 (0.8–
2 (0.8%) (5.8%)
7.1)
(5.4%)
7.6)
33
Referenc
29
Referenc
23.2) Referenc
2014
4 (0.2%) (1.6%)
e
FDRs with CRC
(1.4%)
e
e
<0.001 <0.001
0.606
death 7 (7.3%) Present
4.2 (1.8–
4.8 (2.1–
96
7 (7.3%) 9.6) 40
Absent
0 (0.0%)
–
11.1)
Referenc
35
Referenc
Referenc
2167
6 (0.3%) (1.8%)
e
Number of FDRs
(1.6%)
e
e
0.001 <0.001
0.875
with CRC death 2
1
1
95
0 (0.0%)
–
7 (7.4%)
4.2 (1.8–
0 (0.0%)
40
Referenc
0 (0.0%)
–
0 (0.0%)
–
4.8 (2.1– 7 (7.4%)
9.7) 0
–
11.2) 35
Referenc
2167
Referenc 6 (0.3%)
(1.8%)
e
(1.6%)
e
e
26
CRC-affected parent
<0.001 12
Present
Absent
3.3 (1.7–
<0.001 12
0.572
3.8 (1.9–
1.8 (0.2–
222
1 (0.5%) (5.4%)
6.4)
(5.4%)
7.6)
35
Referenc
30
Referenc
15.8) Referenc
2041
5 (0.2%) (1.7%)
e
CRC-affected
(1.5%)
e
e
0.095 0.592
0.002
sibling 2 (6.3%)
3.3 (0.8–
14.4 1.7 (0.2–
Present
32
14.0)
1 (3.1%)
1 (3.1%)
(1.6–
12.9) 126.5) 45 Absent
Referenc
41
Referenc
Referenc
2231
5 (0.2%) (2.0%)
e
CRC-affected child
(1.8%)
e
–
Present
0
Absent
2263
e –
–
–
–
–
47
Referenc
42
Referenc
– –
– Referenc
6 (0.3%) (2.1%)
e
FDRs with CRC
(1.9%)
e
e
0.492
diagnosed at <50
0.517
0.808
years Present
22
Absent
2241
0 (0.0%)
–
0 (0.0%)
–
47
Referenc
42
Referenc
0 (0.0%)
– Referenc
6 (0.3%) (2.1%)
e
FDRs with CRC
(1.9%)
e
e
0.458
diagnosed at <60
0.940
0.029
years 2 (3.4%) Present
1.7 (0.4–
58
0.9 (0.1– 1 (1.7%)
7.2) 45 Absent
Referenc
7.7 (0.9– 1 (1.7%)
6.8) 41
67.1)
Referenc
2205
Referenc 5 (0.2%)
(2.0%)
e
(1.9%)
e
e
27
Table 4. Relationships between FH of CRC in FDRs and the presence of ACN in screened individuals. Individuals aged 55 to 69 years ACN Number
Figure 1. Flowchart of selection of the data used in this study Figure 2. Adjusted odds ratio of the presence of affected first-degree relatives for advanced colorectal neoplasia according to age of screened individuals. In each age
32
class, the dot indicates the adjusted odds ratio (OR) of the presence of affected first-degree relatives for advanced colorectal neoplasia, and the vertical line shows the range of the 95% confidence interval (CI) of the adjusted OR on a logarithmic scale. The value of the adjusted OR (with 95% CI) is also shown below the dot in each age category.
