Family history of cancer in children and adolescents with germ cell tumours: a report from the Children's Oncology Group.
ABSTRACT: BACKGROUND:Studies of family history of cancer in paediatric germ cell tumours (GCTs) are few, and none has had sufficient sample size to specifically evaluate family history of GCT. METHODS:We utilised family history data from a paediatric GCT study to calculate standardised incidence ratios (SIR) for GCT and other cancers using age- and sex-specific incidence rates from the SEER Program. RESULTS:This analysis included 7998 relatives of paediatric GCT probands. We observed a higher number of GCT cases than expected in male and female relatives of probands (SIR=2.38, 95% CI 1.25, 3.51 for males; SIR=14.3, 95% CI 0.29, 28.4 for females). Further, we observed a particularly strong SIR for relatives of probands with intracranial GCT (SIR=8.07, 95% CI 3.51, 12.6). The SIR for relatives of probands with ovarian GCT was also elevated but did not reach statistical significance (SIR 4.35, 95% CI 0-9.27). Other notable associations include elevated SIRs for melanoma in male relatives and reduced SIRs for lymphatic/haematologic malignancies in male and female relatives. CONCLUSIONS:These results support the hypothesis that familial aggregation of GCT occurs in males and females.
Project description:BACKGROUND:Increased risk of malignancies other than pancreatic cancer (PC) has been reported among first-degree relatives (FDRs) of PC patients; however, the roles of susceptibility gene mutations are unclear. We assessed risk for 15 cancers among FDRs of unselected PC probands. METHODS:Data on 17 162 FDRs, with more than 336 000 person-years at risk, identified through 2305 sequential PC probands enrolled at Mayo Clinic (2000-2016) were analyzed. Family history data were provided by the probands. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated, comparing malignancies observed among the FDRs with that expected using Surveillance, Epidemiology, and End Results (SEER) data. Genetic testing was performed among a subset of probands (n = 2094), enabling stratified analyses among FDRs based on whether the related proband tested positive or negative for inherited mutation in 22 sequenced cancer susceptibility genes. All statistical tests were two-sided. RESULTS:Compared with SEER, PC risk was twofold higher among FDRs of PC probands (SIR = 2.04, 95% CI = 1.78 to 2.31, P < .001). Primary liver cancer risk was elevated among female FDRs (SIR = 2.10, 95% CI = 1.34 to 3.12, P < .001). PC risk was more elevated among FDRs of mutation-positive probands (SIR = 4.32, 95% CI = 3.10 to 5.86) than FDRs of mutation-negative probands (SIR = 1.77, 95% CI = 1.51 to 2.05, between-group P < .001). FDR PC risk was higher when the related proband was younger than age 60 years at diagnosis and mutation-positive (SIR = 5.24, 95% CI = 2.93 to 8.64) than when the proband was younger than age 60 years but mutation-negative (SIR = 1.76, 95% CI = 1.21 to 2.47, between-group P < .001). Breast (SIR = 1.29, 95% CI = 1.01 to 1.63) and ovarian (SIR = 2.38, 95% CI = 1.30 to 4.00) cancers were elevated among FDRs of mutation-positive probands. CONCLUSIONS:Our study substantiates twofold risk of PC among FDRs of PC patients and suggests increased risk for primary liver cancer among female FDRs. FDRs of susceptibility mutation carriers had substantially increased risk for PC and increased risk for breast and ovarian cancers.
Project description:Serrated polyposis (hyperplastic polyposis) is characterized by multiple polyps with serrated architecture in the colorectum. Although patients with serrated polyposis are known to be at increased risk of colorectal cancer (CRC) and possibly extracolonic cancers, cancer risk for their relatives has not been widely explored. The aim of this study was to estimate the risks of CRC and extracolonic cancers for relatives of patients with serrated polyposis.A cohort of the 1,639 first- and second-degree relatives of 100 index patients with serrated polyposis recruited regardless of a family history of polyps or cancer from genetic clinics in Australia, New Zealand, Canada, and the USA, were retrospectively analyzed to estimate the country-, age-, and sex-specific standardized incidence ratios (SIRs) for relatives compared with the general population.A total of 102 CRCs were observed in first- and second-relatives (SIR 2.25, 95% confidence interval (CI) 1.75-2.93; P<0.001), with 54 in first-degree relatives (SIR 5.16, 95% CI 3.70-7.30; P<0.001) and 48 in second-degree relatives (SIR 1.38, 95% CI 1.01-1.91; P=0.04). Six pancreatic cancers were observed in first-degree relatives (SIR 3.64, 95% CI 1.70-9.21; P=0.003). There was no statistical evidence of increased risk for cancer of the stomach, brain, breast, or prostate.Our finding that relatives of serrated polyposis patients are at significantly increased risk of colorectal and pancreatic cancer adds to the accumulating evidence that serrated polyposis has an inherited component.
Project description:Identification of risk factors for venous thromboembolism (VTE) is of utmost importance to improve current prophylactic regimes and treatment guidelines. The extent to which a family history contributes to the risk of VTE needs further exploration.To examine the relative rate of VTE in first-degree relatives compared with the general population.By crosslinking Danish nationwide registries we identified patients with VTE between 1978 and 2012, and their familial relations. The first member in a family to acquire VTE was defined as the proband. All first-degree relatives to probands were followed from the VTE date of the proband and until an event (VTE), death, emigration, 100 year birthday or end of study: 31st of December 2012, whichever came first. The relative rate of VTE was estimated by standardized incidence ratios (SIR) using time-dependent Poisson regression models, with the general population as a fixed reference.We identified 70,767 children of maternal probands, 66,065 children of paternal probands, and 29,183 siblings to sibling probands. Having a maternal proband or a paternal proband were associated with a significantly increased VTE rate of 2.15 (CI: 2.00-2.30) and 2.06 (CI: 1.92-2.21), respectively. The highest estimate of VTE was observed among siblings (adjusted SIR of 2.60 [CI: 2.38-2.83]). Noteworthy, the rate of VTE increased for all first-degree relatives when the proband was diagnosed with VTE in a young age (? 50 years).A family history of VTE was associated with a significantly increased rate of VTE among first-degree relatives compared with the general population.
Project description:Little is known regarding cancer risks for relatives of women with very early-onset breast cancer.We studied 2208 parents and siblings of 504 unselected population-based Caucasian women with breast cancer diagnosed before age 35 years (103 from USA, 124 from Canada and 277 from Australia), 41 known to carry a mutation (24 in BRCA1, 16 in BRCA2 and one in both genes). Cancer-specific standardised incidence ratios (SIRs) were estimated by comparing the number of affected relatives (50% verified overall) with that expected based on incidences specific for country, sex, age and year of birth.For relatives of carriers, the female breast cancer SIRs were 13.13 (95% CI 6.57-26.26) and 12.52 (5.21-30.07) for BRCA1 and BRCA2, respectively. The ovarian cancer SIR was 12.38 (3.1-49.51) for BRCA1 and the prostate cancer SIR was 18.55 (4.64-74.17) for BRCA2. For relatives of non-carriers, the SIRs for female breast, prostate, lung, brain and urinary cancers were 4.03 (2.91-5.93), 5.25 (2.50-11.01), 7.73 (4.74-12.62), 5.19 (2.33-11.54) and 4.35 (1.81-10.46), respectively. For non-carriers, the SIRs remained elevated and were statistically significant for breast and prostate cancer when based on verified cancers.First-degree relatives of women with very early-onset breast cancer are at increased risk of cancers not explained by BRCA1 and BRCA2 mutations.
Project description:The relationship between congenital heart disease (CHD) and malignancies has not been determined. This study aimed to explore the association of CHD with malignancies and examine the risk factors for the development of cancer after a diagnosis of CHD.This nationwide, population-based cohort study on cancer risk evaluated 31,961 patients with newly diagnosed CHD using the Taiwan National Health Insurance Research Database (NHIRD) between 1998 and 2006. The standardized incidence ratios (SIRs) for all and specific cancer types were analyzed, while the Cox proportional hazard model was used to evaluate risk factors of cancer occurrence.Among patients with newly diagnosed CHD regardless of ages, 187 (0.6%) subsequently developed cancers after a diagnosis of CHD. Patients with CHD had increased risk of cancer (SIR, 1.45; 95% CI, 1.25-1.67), as well as significantly elevated risks of hematologic (SIR, 4.04; 95% CI, 2.76-5.70), central nervous system (CNS) (SIR, 3.51; 95% CI, 1.92-5.89), and head and neck (SIR, 1.81; 95% CI, 1.03-2.94) malignancies. Age (HR, 1.06; 95% CI, 1.05-1.06) and co-morbid chronic liver disease (HR, 1.91; 95% CI, 1.27-2.87) were independent risk factors for cancer occurrence among CHD patients.Patients with CHD have significantly increased cancer risk, particularly hematologic, CNS, and head and neck malignancies. Physicians who care for patients with CHD should be aware of their predisposition to malignancy after the diagnosis of CHD. Further studies are warranted to clarify the association between CHD and malignancies.
Project description:BACKGROUND: The value of family history as a risk factor for kidney failure has not been determined in a nationwide setting. AIM: This nationwide family study aimed to determine familial risks for kidney failure in Sweden. METHODS: The Swedish multi-generation register on 0-78-year-old subjects were linked to the Swedish patient register and the Cause of death register for 1987-2010. Individuals diagnosed with acute kidney failure (n?=?10063), chronic kidney failure (n?=?18668), or unspecified kidney failure (n?=?3731) were included. Kidney failure patients with cystic kidney disease, congenital kidney and urinary tract malformations, urolithiasis, and rare inherited kidney syndromes, and hyperoxaluria were excluded. Standardized incidence ratios (SIRs) were calculated for individuals whose parents/siblings were diagnosed with kidney failure compared to those whose parents or siblings were not. RESULTS: The concordant (same disease) familial risks (sibling/parent history) were increased for chronic kidney failure SIR?=?2.02 (95% confidence interval, CI 1.90-2.14) but not for acute kidney failure SIR?=?1.08 (95% CI 0.94-1.22) and for unspecified kidney failure SIR?=?1.25 (95% CI 0.94-1.63). However, the discordant (different disease) familial risk for acute kidney failure SIR?=?1.19 (95% CI 1.06-1.32) and unspecified kidney failure SIR?=?1.63 (95% CI 1.40-1.90) was significantly increased in individuals with a family history of chronic kidney failure. The familial risk for chronic kidney failure was similar for males SIR?=?2.04 (95% CI 1.90-2.20) and females SIR?=?1.97 (95% CI 1.78-2.17). Familial risks for chronic kidney failure were highest at age of 10-19 years SIR?=?6.33 (95% CI 4.16-9.22). CONCLUSIONS: The present study shows that family history is an important risk factor for chronic kidney failure but to a lower degree for acute kidney failure and unspecified kidney failure.
Project description:This study was aimed to characterize the distribution of colorectal cancer risk using family history of cancers by data mining. Family histories for 10,066 colorectal cancer cases recruited to population cancer registries of the Colon Cancer Family Registry were analyzed using a data mining framework. A novel index was developed to quantify familial cancer aggregation. Artificial neural network was used to identify distinct categories of familial risk. Standardized incidence ratios (SIRs) and corresponding 95% confidence intervals (CIs) of colorectal cancer were calculated for each category. We identified five major, and 66 minor categories of familial risk for developing colorectal cancer. The distribution the major risk categories were: (1) 7% of families (SIR = 7.11; 95% CI 6.65-7.59) had a strong family history of colorectal cancer; (2) 13% of families (SIR = 2.94; 95% CI 2.78-3.10) had a moderate family history of colorectal cancer; (3) 11% of families (SIR = 1.23; 95% CI 1.12-1.36) had a strong family history of breast cancer and a weak family history of colorectal cancer; (4) 9 % of families (SIR = 1.06; 95 % CI 0.96-1.18) had strong family history of prostate cancer and weak family history of colorectal cancer; and (5) 60% of families (SIR = 0.61; 95% CI 0.57-0.65) had a weak family history of all cancers. There is a wide variation of colorectal cancer risk that can be categorized by family history of cancer, with a strong gradient of colorectal cancer risk between the highest and lowest risk categories. The risk of colorectal cancer for people with the highest risk category of family history (7% of the population) was 12-times that for people in the lowest risk category (60%) of the population. Data mining was proven an effective approach for gaining insight into the underlying cancer aggregation patterns and for categorizing familial risk of colorectal cancer.
Project description:Importance:Clarification of the joint influence of familial patterns of suicide attempts and comorbid mental disorders can enhance the understanding and prevention of suicide attempts. Objective:To investigate the familial patterns of suicide attempts and comorbid mental disorders and their associations in a 2-site family study of mood and anxiety disorders. Design, Setting, and Participants:Data were obtained from 2 parallel community-based family studies conducted in the United States (National Institute of Mental Health [NIMH] study) and in Lausanne, Switzerland (PsyCoLaus study), on the comorbidity of mood and anxiety disorders. The study sample comprised 1119 adult probands and 5355 first-degree relatives. Data were collected and analyzed from October 2004 to December 2016. Main Outcomes and Measures:Lifetime suicide attempt and mental disorders in first-degree relatives, obtained through direct interviews or family history reports. Results:The study included 1119 adult probands (675 female [60.3%] and a mean [SD] age of 50 [12.0] years) and 5355 first-degree relatives (2752 female [51.4%] and a mean [SD] age of 52 [1.5] years). Of these participants, 90 (8.0%) of 1119 probands and 199 (3.7%) of 5355 relatives had a lifetime history of suicide attempt. Those with such a history had higher rates of all mental disorders, a greater number of disorders, and statistically significantly poorer current and lifetime global functioning. After adjustment for age and sex, a statistically significant association between suicide attempts in probands and in relatives was found at the NIMH site (OR,?2.6; 95% CI,?1.5-4.7), at the Lausanne site (OR, 3.1; 95% CI,?1.6-6.0), and in the combined data (OR,?2.9; 95% CI,?1.9-4.5). All mood disorder subtypes and substance use disorders were statistically significantly associated with suicide attempts. The familial association between lifetime suicide attempts in probands and relatives was not statistically significant for the combined sample (OR,?1.6; 95% CI,?1.0-2.7) after adjustment for comorbid conditions in probands and relatives. Social anxiety disorder in probands was associated with suicide attempts in relatives (OR,?2.4; 95% CI,?1.7-3.5) after controlling for comorbid mood, anxiety, and substance use disorders. Conclusions and Relevance:Familiality of suicide attempts appears to be explained by a history of mental disorders among those with suicide attempts; the novel finding of a common familial diathesis for suicide attempts and social anxiety, particularly in combination with mood disorders, has heuristic value for future research and may be a risk marker that can inform prevention efforts.
Project description:PURPOSE:An association of Lynch syndrome (LS) with breast cancer has been long suspected; however, there have been insufficient data to address this question for each of the LS genes individually. METHODS:We conducted a retrospective review of personal and family history in 423 women with pathogenic or likely pathogenic germ-line variants in MLH1 (N?=?65), MSH2 (N?=?94), MSH6 (N?=?140), or PMS2 (N?=?124) identified via clinical multigene hereditary cancer testing. Standard incidence ratios (SIRs) of breast cancer were calculated by comparing breast cancer frequencies in our study population with those in the general population (Surveillance, Epidemiology, and End Results 18 data). RESULTS:When evaluating by gene, the age-standardized breast cancer risks for MSH6 (SIR?=?2.11; 95% confidence interval (CI), 1.56-2.86) and PMS2 (SIR?=?2.92; 95% CI, 2.17-3.92) were associated with a statistically significant risk for breast cancer whereas no association was observed for MLH1 (SIR?=?0.87; 95% CI, 0.42-1.83) or MSH2 (SIR?=?1.22; 95% CI, 0.72-2.06). CONCLUSION:Our data demonstrate that two LS genes, MSH6 and PMS2, are associated with an increased risk for breast cancer and should be considered when ordering genetic testing for individuals who have a personal and/or family history of breast cancer.
Project description:Studies on treatment modalities for primary hepatic neoplasms (PHN) in Canada are lacking. Our primary aim was to analyze the age-standardized incidence of hepatic resection, ablation, transplantation, and embolization for PHN between 2002 and 2013. Secondary aim was to evaluate temporal trends for these treatment modalities.National Canadian Cancer Registries were accessed for relevant epidemiological data. Age-standardized incidence of treatment ratios (SIRs) was calculated and comparisons were performed for Atlantic Canada, Ontario, the Prairies, and British Columbia.British Columbia recorded the highest SIRs for ablation (1.9; 95% CI 1.8-2.0), hepatic resection (1.2; 95% CI 1.1-1.3), and transarterial locoregional therapies (2.8; 95% CI 2.4-3.2). For hepatic resection, the lowest SIR was found in Atlantic Canada (0.7; 95% CI 0.6-0.9), while the Prairies recorded the lowest estimate for transarterial therapies (0.2; 95% CI 0.1-0.4). Liver transplantation had the highest SIR in Ontario (1.5; 95% CI 1.3-1.6) and the lowest SIR in British Columbia. No significant temporal changes in SIRs were observed for any of the treatments except for transarterial therapies.Treatment of PHN in Canada differs by geography. Variations might be due to differences in expertise or access to therapeutic modalities.