Familial risks of ovarian cancer by age at diagnosis, proband type and histology.
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ABSTRACT:
SUBMITTER: Zheng G
PROVIDER: S-EPMC6169923 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveThere is evidence that parental autoimmune diseases (ADs) are associated with autism spectrum disorders (ASD) in offspring. The association between offspring ASD and ADs diagnosed in siblings and probands remains less clear. We examined whether proband and familial diagnoses of ADs were associated with increased odds of ASD in probands.MethodThe study is based on a nested case-control design that used data from a large national birth cohort (N = 1.2 million) in Finland. There were 4,600 cases of ASD and controls matched 1:4 on date of birth, sex, and residence. Data were accessed from national medical, birth, and central registries.ResultsProbands had a statistically significant increase in odds of ASD when they (adjusted odds ratio [OR] = 1.2), their mother (adjusted OR = 1.1), or their sibling (adjusted OR = 1.2) were diagnosed with an AD. With regard to specific ADs, we found a statistically significant increase in odds of ASD in probands diagnosed with autoimmune thyroiditis (adjusted OR = 2.7). Further analyses considering ADs by body system yielded a statistically significant increase in odds of ASD in probands with ADs associated with the central/peripheral nervous (adjusted OR = 4.8) and skin/mucous membrane (adjusted OR = 1.3) systems. Probands of mothers diagnosed with ear/eye (adjusted OR = 1.6) or respiratory (adjusted OR = 1.4) ADs, or siblings diagnosed with skin/mucous membrane ADs (adjusted OR = 1.3) also had increased odds of ASD.ConclusionThe findings suggest that there may be common pathogenic, developmental mechanisms related to autoimmunity that are associated with the etiology of ASD.
| S-EPMC6631342 | biostudies-literature
Project description:Genetic influences may be discerned in families that have multiple affected members and may manifest as an earlier age of cancer diagnosis. In this study, we determine whether cancers develop at an earlier age in multiplex Familial Barrett's Esophagus (FBE) kindreds, defined by 3 or more members affected by Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC).Information on BE/EAC risk factors and family history was collected from probands at eight tertiary care academic hospitals. Age of cancer diagnosis and other risk factors were compared between nonfamilial (no affected relatives), duplex (two affected relatives), and multiplex (three or more affected relatives) FBE kindreds.The study included 830 nonfamilial, 274 duplex, and 41 multiplex FBE kindreds with 274, 133, and 43 EAC and 566, 288, and 103 BE cases, respectively. Multivariable mixed models adjusting for familial correlations showed that multiplex kindreds were associated with a younger age of cancer diagnosis (P = 0.0186). Median age of cancer diagnosis was significantly younger in multiplex compared with duplex and nonfamilial kindreds (57 vs. 62 vs. 63 years, respectively, P = 0.0448). Mean body mass index was significantly lower in multiplex kindreds (P = 0.0033), as was smoking (P < 0.0001), and reported regurgitation (P = 0.0014).Members of multiplex FBE kindreds develop EAC at an earlier age compared with nonfamilial EAC cases. Multiplex kindreds do not have a higher proportion of common risk factors for EAC, suggesting that this aggregation might be related to a genetic factor.These findings indicate that efforts to identify susceptibility genes for BE and EAC will need to focus on multiplex kindreds.
| S-EPMC3275661 | biostudies-literature
Project description:Familial cancer can be defined through the occurrence of the same cancer in two or more family members. We describe a nationwide landscape of familial cancer, including its frequency and the risk that it conveys, by using the largest family database in the world with complete family structures and medically confirmed cancers. We employed standardized incidence ratios (SIRs) to estimate familial risks for concordant cancer among first-degree relatives using the Swedish Cancer Registry from years 1958 through 2016. Cancer risks in a 20-84 year old population conferred by affected parents or siblings were about two-fold compared to the risk for individuals with unaffected relatives. For small intestinal, testicular, thyroid and bone cancers and Hodgkin disease, risks were higher, five-to-eight-fold. Novel familial associations included adult bone, lip, pharyngeal, and connective tissue cancers. Familial cancers were found in 13.2% of families with cancer; for prostate cancer, the proportion was 26.4%. High-risk families accounted for 6.6% of all cancer families. High-risk family history should be exceedingly considered for management, including targeted genetic testing. For the major proportion of familial clustering, where genetic testing may not be feasible, medical and behavioral intervention should be indicated for the patient and their family members, including screening recommendations and avoidance of carcinogenic exposure.
| S-EPMC8430802 | biostudies-literature
Project description:Venous thromboembolisms (VTEs) have been a leading secondary cause of death among ovarian cancer patients, prompting multiple studies of risk factors. The objective of this meta-analysis is to quantify the associations between VTE and the most commonly reported risk factors among ovarian cancer patients. PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were used to identify observational studies. Two reviewers independently abstracted data and assessed quality via the Newcastle-Ottawa tool. A random effects model was used to calculate the pooled odds ratios for VTE with each of the following exposures: advanced cancer stage, clear cell histology, serous histology, ascites at diagnosis, and complete cytoreduction. The I 2 and Q tests were used to evaluate heterogeneity. Twenty cohort studies with 6,324 total ovarian cancer patients, 769 of whom experienced a VTE, were included. The odds of VTE in ovarian cancer patients were higher among patients with cancer stage III/IV (versus cancer stage I/II, pooled odds ratio (OR) 2.73; 95% CI 1.84-4.06; I 2= 64%), clear cell (versus nonclear cell) histology (OR 2.11; 95% CI 1.55-2.89; I 2 = 6%), and ascites (versus no ascites) at diagnosis (OR 2.12; 95% CI 1.51-2.96; I 2 = 32%). Serous (versus nonserous) histology (OR 1.26; 95% CI 0.91-1.75; I 2 = 42%) and complete (versus incomplete) cytoreduction (OR 1.05; 95% CI 0.27-4.11; I 2 = 88%) were not associated with VTE. This meta-analysis quantifies the significantly elevated odds of VTE in ovarian cancer patients with advanced stage at diagnosis, clear cell histology, and ascites at diagnosis. Further studies are needed to account for confounders and inform clinical decision-making tools.
| S-EPMC7486642 | biostudies-literature
Project description:The identification of hereditary cancer genes for esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), may prove critical for the development of novel prevention and treatment strategies. Specifically, efforts for detecting BE and EAC susceptibility genes have focused on families with three or more affected members, since these individuals have an earlier age onset compared to non-familial individuals. Given that the use of BE may overestimate the likelihood of disease heritability, we evaluated the age of diagnosis in kindreds with a restricted definition including only confirmed high-grade dysplasia (HGD) or EAC. The Familial Barrett's Esophagus Consortium database was used to identify individuals with HGD and EAC. These individuals were subsequently split into three kindred groups: non-familial-a single affected family member, duplex-two affected family members, and multiplex-three or more affected family members. Age of cancer diagnosis and other risk factors were compared between individuals in these groups. The study included 441 non-familial, 46 duplex, and 13 multiplex individuals. There was a statistically significant difference for age of diagnosis for individuals in the multiplex families compared to the non-familial and duplex families (56.0 versus 64.3, 63.5; p = 0.049). There was no significant difference between demographic factors and other cancer risk factors between family types. The results of this study support a genetic basis for familial Barrett's associated neoplasia and evaluation of the genetic susceptibility to this disease should continue to focus on families with multiple (three or more) affected members.
| S-EPMC9469732 | biostudies-literature
Project description:BackgroundThe risk of cancers is well characterized in Lynch syndrome (LS) families but has been less studied in familial colorectal cancer type X (FCCTX) families.MethodsIn this article, we compare the risk estimates of first and second colorectal cancers (CRCs) in 168 FCTTX and 780 LS families recruited through the Colon Cancer Family Registry as well as the risk of cancer-related deaths and disease-free survival (DFS) after a first CRC. Our methodology is based on a survival analysis approach, developed specifically to model the occurrence of successive cancers (ie, first and second CRCs) in the presence of competing risk events (ie, death from any causes).ResultsWe found an excess risk of first and second CRC in individuals with LS compared to FCCTX family members. However, for an average age at first CRC of 60 years in FCCTX families and 50 years in LS families, the DFS rates were comparable in men but lower in women from FCCTX vs LS families, eg , 75.1% (95% confidence interval [CI] = 69.0% to 80.9%) vs 78.9% (95% CI = 76.3% to 81.3%) for the 10-year DFS. The 10-year risk of cancer-related death was higher in FCCTX families vs LS families, eg, 15.4% in men (95% CI = 10.9% to 19.8%) and 19.3% in women (95% CI = 13.6% to 24.7%) vs 8.9% (95% CI = 7.5% to 11.4%) and 8.7% (95% CI = 7.1% to 10.8%), respectively.ConclusionsIndividuals with CRCs arising in the context of FCCTX do not experience the same improved DFS and overall survival of those with LS, and that difference may be relevant in management decisions.
| S-EPMC7514801 | biostudies-literature
Project description:Mutations in the BRCA1 (MIM 113705) gene are found in many families with multiple cases of breast and ovarian cancer, and women with a BRCA1 mutation are at significantly higher risk of developing breast and ovarian cancer than are the general public.We obtained blood samples and pedigree information from 3568 unselected cases of early-onset breast cancer and 609 unselected patients with ovarian cancer from hospitals throughout Poland. Genetic testing was performed for three founder BRCA1 mutations. We also calculated the risk of breast and ovarian cancer to age 75 in the first degree relatives of carriers using Kaplan-Meier methods.The three founder BRCA1 mutations were identified in 273 samples (187 with 5382insC, 22 with 4153delA, and 64 with C61G). A mutation was present in 4.3% of patients with breast cancer and 12.3% of patients with ovarian cancer. The overall risk of breast cancer to age 75 in relatives was 33% and the risk of ovarian cancer was 15%. The risk for breast cancer was 42% higher among first degree relatives of carriers of the C61G missense mutation compared to other mutations (HR = 1.42; p = 0.10) and the risk for ovarian cancer was lower than average (OR = 0.26; p = 0.03). Relatives of women diagnosed with breast cancer had a higher risk of breast cancer than relatives of women diagnosed with ovarian cancer (OR = 1.7; p = 0.03).The risk of breast cancer in female relatives of women with a BRCA1 mutation depends on whether the proband was diagnosed with breast or ovarian cancer.
| S-EPMC2564518 | biostudies-literature
Project description:BACKGROUND:Individuals with pathogenic germline variants in DNA mismatch repair (MMR) genes are at increased risk of developing colorectal, endometrial and other cancers (Lynch syndrome, LS). While previous studies have extensively described cancer risks in LS, cancer risks in individuals from families without detectable MMR gene defects despite MMR deficiency (Lynch-like syndrome, LLS), and in individuals from families fulfilling the Amsterdam-II criteria without any signs of MMR deficiency (familial colorectal cancer type X, FCCX) are less well studied. The aim of this prospective study was to characterise the risk for different cancer types in LS, LLS, and FCCX, and to compare these with the cancer risks in the general population. METHODS:Data was taken from the registry of the German Consortium for Familial Intestinal Cancer, where individuals were followed up prospectively within the framework of an intensified surveillance programme at recommended annual examination intervals. A total of 1120 LS, 594 LLS, and 116 FCCX individuals were analysed. From this total sample, eight different cohorts were defined, in which age-dependent cumulative risks and standardised incidence ratios were calculated regarding the first incident occurrence of any, colorectal, stomach, small bowel, urothelial, female breast, ovarian, and endometrial cancer, separately for LS, LLS, and FCCX. RESULTS:The number of individuals at risk for first incident cancer ranged from 322 to 1102 in LS, 120 to 586 in LLS, and 40 to 116 in FCCX, depending on the cancer type of interest. For most cancer types, higher risks were observed in LS compared to LLS, FCCX, and the general population. Risks for any, colorectal, stomach, urothelial, and endometrial cancer were significantly higher in LLS compared to the general population. No significantly increased risks could be detected in FCCX compared to LLS patients, and the general population. Colorectal and endometrial cancer risks tended to be higher in LLS than in FCCX. CONCLUSIONS:The characterisation of cancer risks in patients with LLS and FCCX is important to develop appropriate surveillance programmes for these specific intermediate risk groups. Larger prospective studies are needed to obtain more precise risk estimates.
| S-EPMC7245918 | biostudies-literature
Project description:This paper presents a robust method to conduct inference in finely stratified familial studies under proband-based sampling. We assume that the interest is in both the marginal effects of subject-specific covariates on a binary response and the familial aggregation of the response, as quantified by intrafamilial pairwise odds ratios. We adopt an estimating function for proband-based family studies originally developed by Zhao and others (1998) in the context of an unstratified design and treat the stratification effects as fixed nuisance parameters. Our method requires modeling only the first 2 joint moments of the observations and reduces by 2 orders of magnitude the bias induced by fitting the stratum-specific nuisance parameters. An analytical standard error estimator for the proposed estimator is also provided. The proposed approach is applied to a matched case-control familial study of sleep apnea. A simulation study confirms the usefulness of the approach.
| S-EPMC2648900 | biostudies-literature
Project description:BackgroundWe analyzed the survival trends for patients with metastatic lung cancer in California.Materials and methodsWe identified patients first diagnosed with primary lung cancer at distant (metastatic) stage in the California Cancer Registry between 1990 and 2014, with follow-up through end of 2015. Race/ethnicity was categorized into non-Hispanic white, non-Hispanic black, Hispanic, and Asian/Pacific Islander. One-year and 5-year relative survival rates were calculated overall and by age at diagnosis, gender, race/ethnicity, and histology during the study period. Joinpoint regression was used to evaluate the trends and to calculate the annual percentage changes (APCs).ResultsA total of 186,156 adults were identified for analysis. Between 1990 and 2014, 1-year relative survival significantly improved from 18.4% to 29.4%, with most improvement observed between 1993 and 2012 (APC, 2.60%; 95% confidence interval, 2.41-2.79; P < .01). Five-year relative survival significantly improved from 2.2% to 5.0%, with an APC of 4.05% (95% confidence interval, 3.47-4.64; P < .01). All age groups experienced an improvement in survival rates. The greatest increases in relative survival were observed among females, Asian/Pacific Islanders, and patients with adenocarcinoma. Yearly survival rates increased for all histologic types over the study period, with adenocarcinoma having the most improvement after 2000.ConclusionsSurvival for patients with metastatic lung cancer in California steadily improved during the 1990 to 2014 period, before the era of lung cancer screening and cancer immunotherapy. The greatest increase in relative survival was observed in those patients who have the most clinical benefit from the history- and biomarker-based precision oncology drugs during the study period.
| S-EPMC8141544 | biostudies-literature