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Parental age and risk of genetic syndromes predisposing to nervous system tumors: nested case-control study.

ABSTRACT: Purpose:Phacomatoses are genetic syndromes that are associated with increased risk of developing nervous system tumors. Phacomatoses are usually inherited, but many develop de novo, with unknown etiology. In this population-based study, we investigated the effect of parental age on the risk of phacomatoses in offspring. Patients and methods:The study was a population-based nested case-control study. All individuals born and residing in Sweden between January 1960 and December 2010 were eligible for inclusion. Using the Patient Register, 4625 phacomatosis cases were identified and further classified as familial or nonfamilial. Ten matched controls per case were randomly selected from the eligible population. Data were analyzed using conditional logistic regression. Analyses were conducted for neurofibromatosis alone (n=2089) and other phacomatoses combined (n=2536). Results:Compared with offspring of fathers aged 25-29 years, increased risk estimates of nonfamilial neurofibromatosis were found for offspring of fathers aged 35-39 years (odds ratio [OR]=1.43 [95% CI 1.16-1.74]) and ?40 years (OR =1.74 [95% CI 1.38-2.19]). For other nonfamilial phacomatoses, the risk estimate for offspring of fathers aged ?40 years was OR =1.23 (95% CI 1.01-1.50). Paternal age was not associated with familial phacomatoses, and no consistent association was observed with maternal age. Conclusion:The findings show a consistent increase in risk of de novo occurrence of phacomatoses predisposing to nervous system tumors in offspring with increasing paternal age, most pronounced for neurofibromatosis, while maternal age did not seem to influence the risk. These findings suggest an increasing rate of new mutations in the NF1 and NF2 genes in spermatozoa of older fathers.

SUBMITTER: Adel Fahmideh M

PROVIDER: S-EPMC6016487 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Parental age and risk of genetic syndromes predisposing to nervous system tumors: nested case-control study.

Adel Fahmideh Maral M Tettamanti Giorgio G Lavebratt Catharina C Talbäck Mats M Mathiesen Tiit T Lannering Birgitta B Johnson Kimberly J KJ Feychting Maria M

Clinical epidemiology 20180620

<h4>Purpose</h4>Phacomatoses are genetic syndromes that are associated with increased risk of developing nervous system tumors. Phacomatoses are usually inherited, but many develop de novo, with unknown etiology. In this population-based study, we investigated the effect of parental age on the risk of phacomatoses in offspring.<h4>Patients and methods</h4>The study was a population-based nested case-control study. All individuals born and residing in Sweden between January 1960 and December 2010 ...[more]

PMID: 29950902

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Project description:BackgroundUse of estrogen-containing menopausal hormone therapy has been shown to influence the risk of central nervous system (CNS) tumors. However, it is unknown how the progestin-component affects the risk and whether continuous versus cyclic treatment regimens influence the risk differently.Methods and findingsNested case-control studies within a nationwide cohort of Danish women followed for 19 years from 2000 to 2018. The cohort comprised 789,901 women aged 50 to 60 years during follow-up, without prior CNS tumor diagnosis, cancer, or contraindication for treatment with menopausal hormone therapy. Information on cumulative exposure to female hormonal drugs was based on filled prescriptions. Statistical analysis included educational level, use of antihistamines, and use of anti-asthma drugs as covariates. During follow-up, 1,595 women were diagnosed with meningioma and 1,167 with glioma. The median (first-third quartile) follow-up time of individuals in the full cohort was 10.8 years (5.0 years to 17.5 years). Compared to never-use, exposure to estrogen-progestin or progestin-only were both associated with increased risk of meningioma, hazard ratio (HR) 1.21; (95% confidence interval (CI) [1.06, 1.37] p = 0.005) and HR 1.28; (95% CI [1.05, 1.54] p = 0.012), respectively. Corresponding HRs for glioma were HR 1.00; (95% CI [0.86, 1.16] p = 0.982) and HR 1.20; (95% CI [0.95, 1.51] p = 0.117). Continuous estrogen-progestin exhibited higher HR of meningioma 1.34; (95% CI [1.08, 1.66] p = 0.008) than cyclic treatment 1.13; (95% CI [0.94, 1.34] p = 0.185). Previous use of estrogen-progestin 5 to 10 years prior to diagnosis yielded the strongest association with meningioma, HR 1.26; (95% CI [1.01, 1.57] p = 0.044), whereas current/recent use of progestin-only yielded the highest HRs for both meningioma 1.64; (95% CI [0.90, 2.98] p = 0.104) and glioma 1.83; (95% CI [0.98, 3.41] p = 0.057). Being an observational study, residual confounding could occur.ConclusionsUse of continuous, but not cyclic estrogen-progestin was associated with increased meningioma risk. There was no evidence of increased glioma risk with estrogen-progestin use. Use of progestin-only was associated with increased risk of meningioma and potentially glioma. Further studies are warranted to evaluate our findings and investigate the influence of long-term progestin-only regimens on CNS tumor risk.

Project description:BackgroundCentral nervous system tumors (CNS) are the most frequent solid tumor in children. Causes of CNS tumors are mainly unknown and only 5% of the cases can be explained by genetic predisposition. We studied the effects of environmental exposure on the incidence of CNS tumors in children by subtype, according to exposure to industrial and/or urban environment, exposure to crops and according to socio-economic status of the child.MethodsWe carried out a population-based case-control study of CNS tumors in Spain, covering 714 incident cases collected from the Spanish Registry of Childhood Tumors (period 1996-2011) and 4284 controls, individually matched by year of birth, sex, and autonomous region of residence. We built a covariate to approximate the exposure to industrial and/or urban environment and a covariate for the exposure to crops (GCI) using the coordinates of the home addresses of the children. We used the 2001 Census to obtain information about socio-economic status (SES). We fitted logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs).ResultsThe results for all CNS tumors showed an excess risk (OR = 1.37; 95%CI = 1.09-1.73) for SES, i.e., children living in the least deprived areas had 37% more risk of CNS tumor than children living in the most deprived areas. For GCI, an increase of 10% in crop surface in the 1-km buffer around the residence implied an increase of 22% in the OR (OR = 1.22; 95%CI = 1.15-1.29). Children living in the intersection of industrial and urban areas could have a greater risk of CNS tumors than children who live outside these areas (OR = 1.20; 95%CI = 0.82-1.77). Living in urban areas (OR = 0.90; 95%CI = 0.65-1.24) or industrial areas (OR = 0.96; 95%CI = 0.81-1.77) did not seem to increase the risk for all CNS tumors together. By subtype, Astrocytomas, Intracranial and intraspinal embryonal tumors, and other gliomas showed similar results.ConclusionOur results suggest that higher socioeconomic status and exposure to crops could increase the risk of CNS tumors in children.

Project description:BackgroundBreast cancer is an umbrella term referring to a group of biologically and molecularly heterogeneous diseases originating from the breast. Globally, incidences of breast cancer has been increasing dramatically over the past decades. Analyses of multiple clinical "big data" can aid us in clarifying the means of preventing the disease. In addition, predisposing risk factors will be the most important issues if we can confirm their relevance. This study aims to provide an overview of the predisposing factors that contribute to a higher possibility of developing breast cancer and emphasize the signs that we ought to pay more attention to.MethodsThis is a matched nested case-control study. The cohort focused on identifying the eligible risk factors in breast cancer development by data screening (2000-2013) from the Taiwan National Health Insurance Research Database (NHIRD) under approved protocol. A total of 486,069 females were enrolled from a nationwide sampled database, and 3281 females was elligible as breast cancer cohort, 478,574 females who had never diagnosed with breast cancer from 2000 to 2013 were eligible as non-breast cancer controls, and matched to breast cancer cases according to age using a 1:6 ratio.ResultsWe analyzed 3281 breast cancer cases and 19,686 non-breast cancer controls after an age-matched procedure. The significant predisposing factors associated with breast cancer development including obesity, hyperlipidemia, thyroid cancer and liver cancer. As for patients under the age of 55, gastric cancer does seem to have an impact on the development of breast cancer; compared with their counterparts over the age of 55, endometrial cancer appears to exhibit an evocative effect.ConclusionsIn this nationwide matched nested case-control study, we identified obesity, hyperlipidemia, previous cancers of the thyroid, stomach and liver as risk factors associated with breast cancer. However, the retrospective nature and limited case numbers of certain cancers still difficult to provide robust evidence. Further prospective studies are necessitated to corroborate this finding in order to nip the disease in the bud.Trial registrationThe studies involving human participants were reviewed and approved by the China Medical University Hospital [CMUH104-REC2-115(AR-4)].

Project description:BackgroundLi-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome caused by germline TP53 gene mutations. It is characterized by high risk of early-onset cancer, and has been confirmed as associated with multiple tumors clinically. So pediatricians should be more alert to LFS in children with tumors. Choroid plexus carcinoma (CPC) is a rare, malignant tumor which account for less than 1% of all central nervous system (CNS) tumors. However, when such tumorigenesis occurs, it is important to be vigilant for the presence of LFS.Case presentationThe first patient is a 32-month-old boy admitted for convulsions and then was found intracranial space-occupying lesion. Underwent operation, he was diagnosis as choroid plexus carcinoma (WHO Grade III). After 5 months, his elder sister, a 13-year-old girl, was brought to emergency department for confusion and intermittent convulsions. Surgery was performed immediately after head CT examination found the lesion. The pathology result indicated glioblastoma. Because the siblings of the same family have successively suffered from malignant tumors, we performed genetic testing on this family. TP53 gene mutation occurred in both children of these two cases from their father, and their other brother was not spared either. So the two siblings both met the diagnostic criteria of LFS. Then they all received systematic anti-tumor therapy, and follow-up hitherto.ConclusionHere we reported a rare LFS case that two siblings were inherited the same TP53 germline mutations from their father. They suffered from choroid plexus carcinoma and glioblastoma and were finally diagnosed with LFS. In this LFS family, the primary tumors of the two children were both central nervous system tumors, which were not reported in the previous literature. It is suggested that clinicians should be alert to LFS related tumors, which is helpful for early diagnosis. Timely detection of TP53 gene is an important way for early diagnosis of LFS, especially in children with tumor. The incidence of secondary tumor in LFS patients is significantly higher, and other family members of the LFS patient also have an increased risk of suffering from the tumors. Therefore, early diagnosis and timely tumor surveillance can obtain better therapeutic effect and prognosis for both proband and their family.

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Parental age and risk of genetic syndromes predisposing to nervous system tumors: nested case-control study.

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Parental age and risk of genetic syndromes predisposing to nervous system tumors: nested case-control study.

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