دورية أكاديمية
Describing patterns of familial cancer risk in subfertile men using population pedigree data.
| العنوان: | Describing patterns of familial cancer risk in subfertile men using population pedigree data. |
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| المؤلفون: | Ramsay JM; Department of Surgery, Division of Urology, University of Utah, Salt Lake City, UT, USA., Madsen MJ; Utah Population Database, University of Utah, Salt Lake City, UT, USA., Horns JJ; Department of Surgery, Division of Urology, University of Utah, Salt Lake City, UT, USA., Hanson HA; Department of Surgery, Division of Urology, University of Utah, Salt Lake City, UT, USA.; Department of Advanced Computing for Health Sciences, Computational Sciences and Engineering Division, Oakridge National Laboratory, Oak Ridge, TN, USA., Camp NJ; Utah Population Database, University of Utah, Salt Lake City, UT, USA.; Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA., Emery BR; Department of Surgery, Division of Urology, University of Utah, Salt Lake City, UT, USA., Aston KI; Department of Surgery, Division of Urology, University of Utah, Salt Lake City, UT, USA., Ferlic E; Intermountain Urological Institute, Salt Lake City, UT, USA., Hotaling JM; Department of Surgery, Division of Urology, University of Utah, Salt Lake City, UT, USA. |
| المصدر: | Human reproduction (Oxford, England) [Hum Reprod] 2024 Apr 03; Vol. 39 (4), pp. 822-833. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 8701199 Publication Model: Print Cited Medium: Internet ISSN: 1460-2350 (Electronic) Linking ISSN: 02681161 NLM ISO Abbreviation: Hum Reprod Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford, UK : Oxford University Press Original Publication: Oxford ; Washington, DC : Published for the European Society of Human Reproduction and Embryology by IRL Press, [c1986- |
| مواضيع طبية MeSH: | Azoospermia*/epidemiology , Azoospermia*/genetics , Azoospermia*/diagnosis , Oligospermia*/epidemiology , Oligospermia*/genetics , Testicular Neoplasms*/epidemiology , Testicular Neoplasms*/genetics, Adolescent ; Young Adult ; Humans ; Male ; Child ; Retrospective Studies ; Pedigree ; Risk Factors |
| مستخلص: | Study Question: Can we simultaneously assess risk for multiple cancers to identify familial multicancer patterns in families of azoospermic and severely oligozoospermic men? Summary Answer: Distinct familial cancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in familial cancer risk by both type of subfertility and within subfertility type. What Is Known Already: Subfertile men and their relatives show increased risk for certain cancers including testicular, thyroid, and pediatric. Study Design, Size, Duration: A retrospective cohort of subfertile men (N = 786) was identified and matched to fertile population controls (N = 5674). Family members out to third-degree relatives were identified for both subfertile men and fertile population controls (N = 337 754). The study period was 1966-2017. Individuals were censored at death or loss to follow-up, loss to follow-up occurred if they left Utah during the study period. Participants/materials, Setting, Methods: Azoospermic (0 × 106/mL) and severely oligozoospermic (<1.5 × 106/mL) men were identified in the Subfertility Health and Assisted Reproduction and the Environment cohort (SHARE). Subfertile men were age- and sex-matched 5:1 to fertile population controls and family members out to third-degree relatives were identified using the Utah Population Database (UPDB). Cancer diagnoses were identified through the Utah Cancer Registry. Families containing ≥10 members with ≥1 year of follow-up 1966-2017 were included (azoospermic: N = 426 families, 21 361 individuals; oligozoospermic: N = 360 families, 18 818 individuals). Unsupervised clustering based on standardized incidence ratios for 34 cancer phenotypes in the families was used to identify familial multicancer patterns; azoospermia and severe oligospermia families were assessed separately. Main Results and the Role of Chance: Compared to control families, significant increases in cancer risks were observed in the azoospermia cohort for five cancer types: bone and joint cancers hazard ratio (HR) = 2.56 (95% CI = 1.48-4.42), soft tissue cancers HR = 1.56 (95% CI = 1.01-2.39), uterine cancers HR = 1.27 (95% CI = 1.03-1.56), Hodgkin lymphomas HR = 1.60 (95% CI = 1.07-2.39), and thyroid cancer HR = 1.54 (95% CI = 1.21-1.97). Among severe oligozoospermia families, increased risk was seen for three cancer types: colon cancer HR = 1.16 (95% CI = 1.01-1.32), bone and joint cancers HR = 2.43 (95% CI = 1.30-4.54), and testis cancer HR = 2.34 (95% CI = 1.60-3.42) along with a significant decrease in esophageal cancer risk HR = 0.39 (95% CI = 0.16-0.97). Thirteen clusters of familial multicancer patterns were identified in families of azoospermic men, 66% of families in the azoospermia cohort showed population-level cancer risks, however, the remaining 12 clusters showed elevated risk for 2-7 cancer types. Several of the clusters with elevated cancer risks also showed increased odds of cancer diagnoses at young ages with six clusters showing increased odds of adolescent and young adult (AYA) diagnosis [odds ratio (OR) = 1.96-2.88] and two clusters showing increased odds of pediatric cancer diagnosis (OR = 3.64-12.63). Within the severe oligozoospermia cohort, 12 distinct familial multicancer clusters were identified. All 12 clusters showed elevated risk for 1-3 cancer types. An increase in odds of cancer diagnoses at young ages was also seen in five of the severe oligozoospermia familial multicancer clusters, three clusters showed increased odds of AYA diagnosis (OR = 2.19-2.78) with an additional two clusters showing increased odds of a pediatric diagnosis (OR = 3.84-9.32). Limitations, Reasons for Caution: Although this study has many strengths, including population data for family structure, cancer diagnoses and subfertility, there are limitations. First, semen measures are not available for the sample of fertile men. Second, there is no information on medical comorbidities or lifestyle risk factors such as smoking status, BMI, or environmental exposures. Third, all of the subfertile men included in this study were seen at a fertility clinic for evaluation. These men were therefore a subset of the overall population experiencing fertility problems and likely represent those with the socioeconomic means for evaluation by a physician. Wider Implications of the Findings: This analysis leveraged unique population-level data resources, SHARE and the UPDB, to describe novel multicancer clusters among the families of azoospermic and severely oligozoospermic men. Distinct overall multicancer risk and familial multicancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in cancer risk by type of subfertility and within subfertility type. Describing families with similar cancer risk patterns provides a new avenue to increase homogeneity for focused gene discovery and environmental risk factor studies. Such discoveries will lead to more accurate risk predictions and improved counseling for patients and their families. Study Funding/competing Interest(s): This work was funded by GEMS: Genomic approach to connecting Elevated germline Mutation rates with male infertility and Somatic health (Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): R01 HD106112). The authors have no conflicts of interest relevant to this work. Trial Registration Number: N/A. (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.) |
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| معلومات مُعتمدة: | HHSN261201800016C United States CA NCI NIH HHS; HHSN261201800016I United States CA NCI NIH HHS; NU58DP007131 United States CC CDC HHS; R01 HD106112 United States HD NICHD NIH HHS |
| فهرسة مساهمة: | Keywords: cancer risk patterns; familial cancer risk; fertility and cancer; male fertility; subfertility |
| تواريخ الأحداث: | Date Created: 20240221 Date Completed: 20240404 Latest Revision: 20240426 |
| رمز التحديث: | 20240426 |
| مُعرف محوري في PubMed: | PMC10988109 |
| DOI: | 10.1093/humrep/dead270 |
| PMID: | 38383051 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1460-2350 |
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| DOI: | 10.1093/humrep/dead270 |