scholarly journals Familial colorectal cancer risk in half siblings and siblings: nationwide cohort study

BMJ ◽  
2019 ◽  
pp. l803 ◽  
Author(s):  
Yu Tian ◽  
Elham Kharazmi ◽  
Kristina Sundquist ◽  
Jan Sundquist ◽  
Hermann Brenner ◽  
...  

AbstractObjectiveTo 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.DesignAmbidirectional cohort study.SettingNationwide Swedish Family Cancer Data (record linkage).ParticipantsAll 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 measuresLifetime (0-79 years) cumulative risk and standardised incidence ratio of colorectal cancer among first degree relatives and second degree relatives.ResultsThe 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.ConclusionFamily 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.

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2299-2299
Author(s):  
Karine Gauthier ◽  
Elham Sabri ◽  
Susan R. Kahn ◽  
Philip S Wells ◽  
David Anderson ◽  
...  

Abstract Abstract 2299 Introduction: The duration of anticoagulation after unprovoked venous thromboembolism (VTE) has been characterized as the most important unanswered question in clinical thrombosis management. This has led to research to identify predictors of recurrent VTE to identify high-risk patients who might warrant indefinite anticoagulation. Many clinicians assume that a family history of VTE is a predictor of recurrent VTE. This study aims to assess the value of family history as a predictor for recurrent VTE. Methods: Prospective multi-center multi-national cohort study recruited patients with a first objectively proven unprovoked VTE who completed 5 to 7 months of anticoagulation therapy. A detailed family history of VTE was completed for every subject. The information recorded included the number of affected relatives, whether they were first or second degree relatives and if the VTE was unprovoked or secondary. Patients were then followed for recurrent VTE. Results: 664 subjects were enrolled between October 2001 and March 2006, 649 subjects were followed for a mean duration of 3.8 years (3.6–3.98 95% C.I.). The mean age of subjects in this cohort was 53 years (min-max 18–95) and 49% of subjects were females. A family history of VTE in at least 1 first-degree relative was recorded for 112 (17.3%) subjects. A total of 142 (21.9%) suspected VTE events were adjudicated as recurrences. The recurrence rate was 5.94% (4.89–7.15 95% C.I.) per patient-year for patients without any family history of VTE, and it was 4.82% (3.02–7.30 95% C.I.) per patient-year in patients with a family history of VTE in at least 1 first-degree relative. In secondary analyses, neither a family history of unprovoked VTE, multiple unprovoked VTE, in first-degree nor second-degree relatives was a predictor of recurrent VTE. A multivariate analysis was performed to adjust for known risk factors for VTE recurrence, but the adjusted hazard ratios were again not significantly different. Conclusion: A family history of VTE is not a predictor for recurrent VTE, and therefore should not be used to segregate unprovoked VTE patients in high- and low-risk categories. Disclosures: No relevant conflicts of interest to declare.


2013 ◽  
Vol 95 (8) ◽  
pp. 586-590 ◽  
Author(s):  
JK Randall ◽  
CS Good ◽  
JM Gilbert

Introduction We report the outcomes of a long-term surveillance programme for individuals with a family history of colorectal cancer. Methods The details of patients undergoing a colonoscopy having been referred on the basis of family history of colorectal cancer were entered prospectively into a database. Further colonoscopy was arranged on the basis of the findings. The outcomes assessed included incidence of cancer and adenoma identification at initial and subsequent colonoscopy. Results The records of 2,293 patients (917 men; median patient age: 51 years) were entered over 22 years, giving data on 3,982 colonoscopies. Eight adverse events (0.2%) were recorded. Twenty-seven cancers were found at first colonoscopy and thirteen developed during the follow-up period. There were significantly more cancers identified in those with more than one first-degree relative with cancer than in other groups (p=0.01). The number of adenomas identified at subsequent surveillance colonoscopies remained constant with between 9.3% and 12.0% of patients having adenomas that were removed. Two-thirds (68%) of patients with cancer and three-quarters (77%) with adenomas fell outside the British Society of Gastroenterology (BSG) 2006 guidelines. Conclusions Repeated colonoscopy continues to yield significant pathology including new cancers. These continue to occur despite removal of adenomas at prior colonoscopies. The majority of patients with cancers and adenomas fell outside the BSG 2006 guidelines; more would have fallen outside the 2010 guidelines.


2009 ◽  
Vol 125 (4) ◽  
pp. 918-925 ◽  
Author(s):  
Ji-Hyun Jang ◽  
Michelle Cotterchio ◽  
Steven Gallinger ◽  
Julia A. Knight ◽  
Darshana Daftary

Author(s):  
Yu Tian ◽  
Elham Kharazmi ◽  
Hermann Brenner ◽  
Xing Xu ◽  
Kristina Sundquist ◽  
...  

Background: The aim of this study was to explore the risk of invasive colorectal cancer (CRC) in relatives of patients with colorectal carcinoma in situ (CCIS), which is lacking in the literature. Patients and Methods: We collected data from Swedish family-cancer datasets and calculated standardized incidence ratio (SIR) and cumulative risk of CRC in family histories of CCIS in first- and second-degree relatives. Family history was defined as a dynamic (time-dependent) variable allowing for changes during the follow-up period from 1958 to 2015. Of 12,829,251 individuals with available genealogical data, 173,796 were diagnosed with CRC and 40,558 with CCIS. Results: The lifetime (0–79 years) cumulative risk of CRC in first-degree relatives of patients with CCIS was 6.5%, which represents a 1.6-fold (95% CI, 1.5–1.7; n=752) increased risk. A similarly increased lifetime cumulative risk (6.7%) was found among first-degree relatives of patients with CRC (SIR, 1.6; 95% CI, 1.6–1.7; n=6,965). An increased risk of CRC was also found in half-siblings of patients with CCIS (SIR, 1.9; 95% CI, 1.1–3.0; n=18) and also in half-siblings of patients with CRC (SIR, 1.7; 95% CI, 1.3–2.1; n=78). Moreover, the increased risk of CRC was higher for younger age at diagnosis of CCIS in the affected first-degree relative and for younger age at diagnosis of CRC in the index person. Conclusions: Results of this study show that first-degree relatives and half-siblings of patients with CCIS have an increased risk of CRC, which is comparable in magnitude to the risk of those with a family history of invasive CRC. These findings extend available evidence on familial risk of CRC and may help to refine guidelines and recommendations for CRC screening.


2011 ◽  
Vol 18 (03) ◽  
pp. 344-349
Author(s):  
MUTAHIR A. TUNIO ◽  
ALTAF HASHMI ◽  
REHAN MOHSIN ◽  
Gohar Sultan

Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common form of hereditary bowel cancer. Multiple generations are affected with colorectal cancer at relatively young age, between 25 and 45 years. Objective: To investigate the frequency of HNPCC in Pakistani population, due to the high incidence of colorectal cancer in younger Pakistani adults and prevalence of consanguinity in this region conducted this study. Period: November 2008 and January 2010. Methodology: Ninty histopathologically confirmed colorectal cancer patients between 12- 50 years and their families were interviewed using a detailed questionaire. The questions about family history of colorectal cancer, history of other cancers, age at diagnosis and consanguinity were asked. The pedigrees were drawn for all families based on given information. Hospital records were also reviewed to confirm cancers reported in relatives. Amsterdam criteria was used to label a family as HNPCC. Results: Seventeen patients (18.9%) had one or more first or second degree relatives under age 50 years with colorectal cancers suggestive of HNPCC. Another 15 patients (16.7%) had first or second degree relatives with a family history of other extra-colonic cancers including ovarian, breast, endometrium, lung, parotid, brain and bladder cancer. Of these 30 patients (33.3%) reported that their parents were first degree cousins. Conclusions: 1. High frequency of HNPCC is seen in Pakistani population. 2. Higher proportion of colorectal cancer is seen in young Pakistanis. Strong prevalence of consanguineous marriages could be important factors for HNPCC occurrence in Pakistan. Future studies with large sample size along with genetic testing and screening programmes are warranted. 


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10542-10542
Author(s):  
Zhe Pan ◽  
Junfeng Huang ◽  
Mingkai Huang ◽  
Zhiyuan Yao ◽  
Jiongqiang Huang ◽  
...  

10542 Background: The incidence of colorectal cancer among persons aged < 50 years (early-onset colorectal cancer, EOCRC) has increased since the early 1990s. However, the risk factors contributing to this trend remain largely unknown. Methods: We conducted a retrospective study of participants who were aged < 50 years and without a previous cancer history, using the China Kadoorie Biobank cohort study. We analyzed data related to demographics, lifestyle habits, family history, and comorbidities of EOCRC cases with participants without colorectal cancer in this age group (controls). Univariate and multivariate-adjusted cox regression models were used to estimate the associations with risk factors. Results: We identified 225 EOCRC cases and 88842 controls that include the final analyses. Of the 225 EOCRC patients, 105 (46.7%) were colon cancers and 120 (53.3%) were rectum cancers. EOCRC cases were older, have more intake of fish and eggs, have higher BMIs, diabetes, and family history of cancer compared with controls (P < 0.05). After adjustment for potential confounding factors, increasing age (HR 2.18, 95%CI 2.05-2.31), BMI (HR 1.06, 95%CI 1.01-1.11), family history of cancer (HR 1.41, 95%CI 1.00-1.98), and more intake of fish (HR 1.54, 95%CI 1.09-2.19) were significantly associated with a higher risk of EOCRC. In sensitivity analyses stratified by cancer site (colon and rectum), the results remained consistent. Conclusions: Based on the large Chinese cohort study, we found increasing age, higher BMI or obesity, family history of cancer, and more intake of fish were independent risk factors for EOCRC. Further studies are needed to identify factors that cause the increasing incidence of EOCRC in China and other countries, and explore the potential mechanism behind.[Table: see text]


2006 ◽  
Vol 24 (34) ◽  
pp. 5395-5402 ◽  
Author(s):  
Louise S. Acheson ◽  
Stephen J. Zyzanski ◽  
Kurt C. Stange ◽  
Amy Deptowicz ◽  
Georgia L. Wiesner

Purpose A detailed family history is important for cancer risk assessment, but obtaining it is time consuming and infrequently accomplished in practice. The Genetic Risk Easy Assessment Tool (GREAT) conducts a computer-administered family history interview and immediately generates a pedigree diagram in digital form. The purpose of this study was to validate family cancer histories produced by patients using the computer tool in comparison with pedigrees made by genetic counselors. Methods Patients scheduled for genetics consultation recorded their family histories using the GREAT, separate from their genetic counseling session. The presence of each relative; presence, type, and age at diagnosis of cancers; and cancer geneticist's risk assessment were compared for 120 pairs of pedigrees produced by counselors versus computer tool. Results The automated telephone interview took a mean of 33.5 minutes and was highly acceptable to respondents. Ninety-four percent of first-degree relatives, 67% of second-degree relatives, and 38% of third-degree relatives were identical on paired pedigrees; computer-generated pedigrees included additional relatives. Sixty-three percent of all cancers were identified by both family histories, with 90% agreement on the type of cancer. There was very good agreement (κ = 0.70; correlation = 0.77) between the geneticist's breast cancer risk assessments based on computer versus counselors' pedigrees. In a subsample of 61 users, test-retest reliability for the computer-administered questionnaire was high (φ = 0.94 for cancers in first-degree and φ = 0.91 in second-degree relatives). Conclusion The GREAT computer-administered questionnaire provides an acceptable, reliable, and valid way of collecting an unverified but extensive family history of cancer and displaying it as a pedigree, in an entirely automated process.


PLoS Medicine ◽  
2020 ◽  
Vol 17 (11) ◽  
pp. e1003431
Author(s):  
Uzair Ali Khan ◽  
Mahdi Fallah ◽  
Kristina Sundquist ◽  
Jan Sundquist ◽  
Hermann Brenner ◽  
...  

Background Colorectal cancer (CRC) incidence is increasing among young adults below screening age, despite the effectiveness of screening in older populations. Individuals with diabetes mellitus are at increased risk of early-onset CRC. We aimed to determine how many years earlier than the general population patients with diabetes with/without family history of CRC reach the threshold risk at which CRC screening is recommended to the general population. Methods and findings A nationwide cohort study (follow-up:1964–2015) involving all Swedish residents born after 1931 and their parents was carried out using record linkage of Swedish Population Register, Cancer Registry, National Patient Register, and Multi-Generation Register. Of 12,614,256 individuals who were followed between 1964 and 2015 (51% men; age range at baseline 0–107 years), 162,226 developed CRC, and 559,375 developed diabetes. Age-specific 10-year cumulative risk curves were used to draw conclusions about how many years earlier patients with diabetes reach the 10-year cumulative risks of CRC in 50-year-old men and women (most common age of first screening), which were 0.44% and 0.41%, respectively. Diabetic patients attained the screening level of CRC risk earlier than the general Swedish population. Men with diabetes reached 0.44% risk at age 45 (5 years earlier than the recommended age of screening). In women with diabetes, the risk advancement was 4 years. Risk was more pronounced for those with additional family history of CRC (12–21 years earlier depending on sex and benchmark starting age of screening). The study limitations include lack of detailed information on diabetes type, lifestyle factors, and colonoscopy data. Conclusions Using high-quality registers, this study is, to our knowledge, the first one that provides novel evidence-based information for risk-adapted starting ages of CRC screening for patients with diabetes, who are at higher risk of early-onset CRC than the general population.


2011 ◽  
Vol 29 (28) ◽  
pp. 3747-3752 ◽  
Author(s):  
Cezary Cybulski ◽  
Dominika Wokołorczyk ◽  
Anna Jakubowska ◽  
Tomasz Huzarski ◽  
Tomasz Byrski ◽  
...  

Purpose To estimate the risk of breast cancer in a woman who has a CHEK2 mutation depending on her family history of breast cancer. Patients and Methods Seven thousand four hundred ninety-four BRCA1 mutation–negative patients with breast cancer and 4,346 control women were genotyped for four founder mutations in CHEK2 (del5395, IVS2+1G>A, 1100delC, and I157T). Results A truncating mutation (IVS2+1G>A, 1100delC, or del5395) was present in 227 patients (3.0%) and in 37 female controls (0.8%; odds ratio [OR], 3.6; 95% CI, 2.6 to 5.1). The OR was higher for women with a first- or second-degree relative with breast cancer (OR, 5.0; 95% CI, 3.3 to 7.6) than for women with no family history (OR, 3.3; 95% CI, 2.3 to 4.7). If both a first- and second-degree relative were affected with breast cancer, the OR was 7.3 (95% CI, 3.2 to 16.8). Assuming a baseline risk of 6%, we estimate the lifetime risks for carriers of CHEK2 truncating mutations to be 20% for a woman with no affected relative, 28% for a woman with one second-degree relative affected, 34% for a woman with one first-degree relative affected, and 44% for a woman with both a first- and second-degree relative affected. Conclusion CHEK2 mutation screening detects a clinically meaningful risk of breast cancer and should be considered in all women with a family history of breast cancer. Women with a truncating mutation in CHEK2 and a positive family history of breast cancer have a lifetime risk of breast cancer of greater than 25% and are candidates for magnetic resonance imaging screening and for tamoxifen chemoprevention.


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