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Cancer risk in first- and second-degree relatives of men with poor semen quality.

ABSTRACT: OBJECTIVE:To further characterize the association of male infertility with health risks by evaluating semen quality and cancer risk in family members. DESIGN:Retrospective, cohort study. SETTING:Not applicable. PATIENT(S):A total of 12,889 men undergoing SA and 12,889 fertile control subjects that had first-degree relative (FDR) data (n = 130,689) and 8,032 men with SA and 8,032 fertile control subjects with complete second-degree relative (SDR) data (n = 247,204) were identified through the UPDB. An equal number of fertile population control subjects were matched. INTERVENTIONS:None. MAIN OUTCOME MEASURE(S):Adult all-site, testicular, thyroid, breast, prostate, melanoma, bladder, ovarian, and kidney cancer diagnoses in FDRs and SDRs. RESULT(S):The FDRs of men with SA had a 52% increased risk of testicular cancer compared with the FDRs of fertile population control subjects. There was no significant difference in testicular cancer risk for the SDRs based on any of the semen parameters. The FDRs and SDRs of azoospermic men had a significantly increased risk of thyroid cancer compared with fertile population control subjects. CONCLUSION(S):These data suggest a link between male infertility and selected cancer risk in relatives. This highlights the possibilities of shared biologic mechanisms between the two diseases, exposure to environmental factors, and an increased level of genetic and/or epigenetic burden in subfertile men and their relatives that may be associated with risk of cancer.

SUBMITTER: Anderson RE

PROVIDER: S-EPMC5617641 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Cancer risk in first- and second-degree relatives of men with poor semen quality.

Anderson Ross E RE Hanson Heidi A HA Patel Darshan P DP Johnstone Erica E Aston Kenneth I KI Carrell Douglas T DT Lowrance William T WT Smith Ken R KR Hotaling James M JM

Fertility and sterility 20160620 3

<h4>Objective</h4>To further characterize the association of male infertility with health risks by evaluating semen quality and cancer risk in family members.<h4>Design</h4>Retrospective, cohort study.<h4>Setting</h4>Not applicable.<h4>Patient(s)</h4>A total of 12,889 men undergoing SA and 12,889 fertile control subjects that had first-degree relative (FDR) data (n = 130,689) and 8,032 men with SA and 8,032 fertile control subjects with complete second-degree relative (SDR) data (n = 247,204) we ...[more]

PMID: 27336212

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Project description:BackgroundMutations in the BRCA1 and BRCA2 genes are associated with increased risk of breast, ovarian, and several other cancers. The purpose of the present study was to evaluate the incidence of cancer in first- and second-degree relatives of BRCA mutation carriers compared with the general population.Materials and methodsA total of 1,086 pedigrees of BRCA mutation carriers was obtained from a prospectively maintained, internal review board-approved study of persons referred for clinical genetic counseling at the University of Texas MD Anderson Cancer Center. We identified 9,032 first- and second-degree relatives from 784 pedigrees that had demonstrated a clear indication of parental origin of mutation. Standardized incidence ratios (SIRs) were used to compare the observed incidence of 20 primary cancer sites to the expected incidence of each cancer based on the calculated risk estimates according to each subject's age, sex, and ethnicity.ResultsBRCA1 families had increased SIRs for breast and ovarian cancer (p < .001) and decreased SIRs for kidney, lung, prostate, and thyroid cancer and non-Hodgkin's lymphoma (p < .001). BRCA2 families had increased SIRs for breast, ovarian, and pancreatic cancer (p < .001) and decreased SIRs for kidney, lung, thyroid, and uterine cancer and non-Hodgkin's lymphoma (p < .0025). Analysis of only first-degree relatives (n = 4,099) identified no decreased SIRs and agreed with the increased SIRs observed in the overall study population.ConclusionWe have confirmed previous reports of an association between breast, ovarian, and pancreatic cancers with BRCA mutations. Additional research to quantify the relative risks of these cancers for BRCA mutation carriers can help tailor recommendations for risk reduction and enhance genetic counseling.Implications for practiceBRCA gene mutations have been well described to carry an increased risk of both breast and ovarian cancer. However, the implications and risks of other cancers continues to be investigated. Evaluating the risks for other cancers further is key in identifying and managing risk reduction strategies.

Project description:ImportanceAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative condition primarily involving the motor system. There is increasing epidemiologic evidence of an association between ALS and a wider spectrum of neurodegenerative and neuropsychiatric disorders among family members, including schizophrenia and psychotic illness and suicidal behavior.ObjectiveTo examine the frequency and range of neuropsychiatric conditions that occur within individual first-degree and second-degree relatives of patients with ALS.Design, setting, and participantsIn this population-based, case-control family aggregation study, all 202 patients included in the Irish ALS Register between January 1, 2012, and January 31, 2014, with definite, probable, or possible ALS as defined by El Escorial criteria were invited to participate. A total of 75 patients were unable or refused to participate and were excluded; the remaining 127 patients with incident ALS were genotyped for the C9orf72 repeat expansion and 132 age- and sex-matched controls were included in the study.Main outcome and measuresThe prevalence of defined neuropsychiatric disease in first-degree and second-degree relatives of patients with ALS and matched controls was determined.ResultsMean (SD) age at diagnosis of the 127 patients in the study (58 women and 69 men) was 64.2 (10.7) years. Data from 2116 relatives of patients with ALS were reported, including 924 first-degree relatives, 1128 second-degree relatives, and 64 third-degree relatives. Data from controls were reported from 829 first-degree and 1310 second-degree relatives. A total of 77 patients with ALS (61.4%) and 51 control participants (38.6%) reported at least 1 first-degree or second-degree relative with a history of schizophrenia, psychosis, suicide, depression, alcoholism, or autism (relative risk [RR], 1.50; 95% CI, 1.08-2.17; P = .02). Cluster analysis suggested the following 2 subgroups based on the number of family members with a neuropsychiatric condition: expected (0-2) and high (≥3). Within the high subgroup, ALS kindreds presented a significantly higher rate of psychiatric illness than did controls (28 of 39 [71.8%]; mean [SD] number of siblings, 4.29 [1.41]; P = .001). A strong family history of schizophrenia (RR, 3.40; 95% CI, 1.27-9.30; P = .02), suicide (RR, 3.30; 95% CI, 1.07-10.05; P = .04), autism (RR, 10.10; 95% CI, 1.30-78.80; P = .03), and alcoholism (RR, 1.48; 95% CI, 1.01-2.17; P = .045) was reported in ALS kindreds. A total of 5 of 29 probands (17.2%) with a strong family history of neuropsychiatric conditions (≥3 first-degree or second-degree relatives) carried the C9orf72 repeat expansion.Conclusions and relevanceNeuropsychiatric symptoms in addition to schizophrenia, including obsessive-compulsive disorder, autism, and alcoholism, occur more frequently in ALS kindreds than in controls. The presence of the C9orf72 repeat expansion does not fully account for this finding, suggesting the presence of additional pleiotropic genes associated with both ALS and neuropsychiatric disease in the Irish population.

Dataset Information

Cancer risk in first- and second-degree relatives of men with poor semen quality.

Publications

Cancer risk in first- and second-degree relatives of men with poor semen quality.

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