scholarly journals Importance of Family History of Colorectal Carcinoma In Situ Versus Invasive Colorectal Cancer: A Nationwide Cohort Study

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.

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Trasias Mukama ◽  
Mahdi Fallah ◽  
Hermann Brenner ◽  
Xing Xu ◽  
Kristina Sundquist ◽  
...  

Abstract Background Wide implementation of mammography screening has resulted in increased numbers of women diagnosed with breast carcinoma in situ. We aimed to determine the risk of invasive breast cancer in relatives of patients with breast carcinoma in situ in comparison to the risk in relatives of patients with invasive breast cancer. Methods We analyzed the occurrence of cancer in a nationwide cohort including all 5,099,172 Swedish women born after 1931 with at least one known first-degree relative. This was a record linkage study of Swedish family cancer datasets, including cancer registry data collected from January 1, 1958, to December 31, 2015. We calculated standardized incidence ratios (SIRs) and 10-year cumulative risk of breast cancer diagnosis for women with a family history of in situ and invasive breast cancer. Results Having one first-degree relative with breast carcinoma in situ was associated with 50% increased risk of invasive breast cancer (SIR = 1.5, 95% CI 1.4–1.7) when compared to those who had no family history of invasive breast cancer or breast carcinoma in situ in either first- or second-degree relatives. Similarly, having one first-degree relative with invasive breast cancer was associated with 70% (1.7, 1.7–1.8) increased risk. The 10-year cumulative risk for women at age 50 with a relative with breast carcinoma in situ was 3.5% (2.9–3.9%) and was not significantly different from 3.7% (3.6–3.8%) risk for 50-year-old women with a relative with invasive breast cancer (95% confidence intervals overlapped). Conclusions The risk of invasive breast cancer for women with a family history of breast carcinoma in situ was comparable to that for women with a family history of invasive breast cancer. Therefore, family history of breast carcinoma in situ should not be overlooked in recommendations for breast cancer prevention for women with a family history of breast cancer.


2020 ◽  
Vol 7 (3) ◽  
pp. 482
Author(s):  
J. K. Deshmukh ◽  
P. Y. Mulay ◽  
Amit G. Naghate ◽  
Anant A. Takalkar

Background: There is steady increase in the prevalence of diabetes mellitus from 0.73% to current 2.4% in rural and 4.0% to 11.6% in urban areas. Familial clustering of diabetes may support a genetic predisposition to diabetes. With increase in the prevalence of diabetes there is increase in number of first degree relative as well, thus an increased risk of developing diabetes, will also increase. To study the plasma glucose levels in First-degree relatives of family member of type 2 diabetic patients was the objective of the present study.Methods: It is a descriptive observational study with 1020 individuals serially coming to our outpatient Department for Pre-employment Medical Health Check Up Annual Health Check Up were selected. These individuals have been enrolled for the study and their family history of diabetes was noted, their sugar levels and their lipid levels were estimated and their body mass index was calculated. The data thus collected and analyzed with excel.Results: 184 (18%) individuals were FDRs, were as 836 (82%) individuals were Non-FDRs. There were 754 (74%) males [131(17%) FDR and 623(83%) Non-FDR], were as 213 (26%) females [53(20%) FDR and 213(80%) Non-FDR], 61(6%) individuals were having Diabetic Mother, 91(9%) individuals had Diabetic Father and 32(3%) were those in whom both the Parents were Diabetic. It was found that maternal history has strong association for getting abnormal BSL levels as compared to a diabetic father as the RR of 9.82 (95% 4.84 to 19.95) in individuals with mother being diabetic, and RR of 1.54(95% 0.68 to 3.87) of father being diabetic.Conclusions: Family history of diabetes, maternal history of diabetes and history of both the parents having diabetes are risk factors for diabetes in FDRs.


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.


2016 ◽  
Vol 27 ◽  
pp. vi191 ◽  
Author(s):  
S. Ahmed ◽  
S.Y.A. Kazmi ◽  
M.E. Emara ◽  
T. Asif ◽  
R. Alvi ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1513-1513
Author(s):  
Amanda S. Bruegl ◽  
Bojana Djordjevic ◽  
Shannon Neville Westin ◽  
Pamela T. Soliman ◽  
Amanda C. Brandt ◽  
...  

1513 Background: Hereditary colorectal cancer (CRC) is preventable; however, identification of individuals at sufficiently high risk to warrant heightened surveillance is difficult. Lynch Syndrome (LS) is an inherited cancer syndrome due to germline mutation in a DNA mismatch repair gene. For women with LS, the lifetime risk of endometrial cancer (EC) is 64% and CRC is 54%. Fifty percent of women with LS will present with EC or ovarian cancer prior to CRC. Therefore, women with LS associated EC represent an ideal group for CRC prevention. The optimal method to identify women with LS associated EC is not known. The purpose of this study was to determine the utility of Amsterdam II and Society of Gynecologic Oncology (SGO) Criteria (modified Bethesda criteria that use EC as the sentinel cancer) in identifying women with LS associated EC. Our ultimate goal is to identify women at increased risk of CRC. Methods: Immunohistochemistry (IHC) for DNA mismatch repair proteins and MLH1 methylation analyses were used to identify LS associated EC among 388 women. EC was designated as LS if there was loss of mismatch repair protein expression. Absence of MLH1 methylation was required to confirm LS in tumors with MLH1 protein loss. Results: Fifty-nine (15.2%) of the EC patients tested had LS. These patients are summarized in the table. Conclusions: Clinical criteria to detect LS identify 17/59 (29%) - 44/59 (74%) of women who present with EC first. EC with MSH2 loss is most likely to occur in younger women and women with positive family history of EC and CRC, features classically associated with LS. In general, the MSH6 mutation is associated with older age at diagnosis and fewer familial CRCs, however, we found a large number of MLH1 (50%) and PMS2 (86%) cases diagnosed at greater than 50 years with no family history of CRC. Our data suggest that classic clinical screening criteria are inadequate to detect patients with LS who present with EC, potentially missing up to 25% of these patients. [Table: see text]


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