Male Subfertility and Prostate Cancer Risk: Epidemiological and Genetic Studies
Author
Summary, in English
Our specific aims were to investigate: 1) whether the AR codon repeats are associated with clinical reproductive parameters, subfertility, hypospadias, or cryptorchidism; 2) whether childlessness secondary to male subfertility is associated with reduced PCa risk; and 3) the possible involvement of genetic variants in reducing PCa risk in subfertile men, including in the sex steroid signaling pathway and aryl hydrocarbon receptor (AHR) pathway, which mediates some of the effects of endocrine disrupting chemicals, and also in PCa risk genes implicated in previous genome-wide association studies.
Our main findings were that: 1) GGN repeat lengths were significantly longer in men with penile hypospadias or cryptorchidism than in controls (median 24 vs. 23) and that the longer allele may be associated with superior AR function; 2) subfertile men were at reduced PCa risk compared with fertile men, OR: 0.45 (95% CI: 0.25-0.83); and 3) genes harboring variants that may play a role in reducing PCa risk in subfertile men include AHR, its partner molecule AHR nuclear translocator (ARNT), and estrogen receptor beta (ESR2), as well as a number of other genes, of which poly (ADP-ribose) polymerase 2 (PARP2) showed the most robust association.
We conclude that: 1) longer GGN repeat lengths may be associated with cryptorchidism and hypospadias; 2) subfertile involuntarily childless men are at an approximately 50% lower risk of being diagnosed with PCa than are fathers of at least one biological child; 3) variants in a number of genes may play a role in linking male subfertility with reduced PCa risk through their associations with impaired reproductive function. The findings support the hypothesis that alterations in sex steroid action, potentially via interaction with the AHR-ARNT signaling pathway, may contribute to the overall reduction in PCa risk in subfertile men.
Department/s
Publishing year
2012
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2012:5
Full text
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Document type
Dissertation
Publisher
Lund University: Faculty of Medicine
Topic
- Obstetrics, Gynecology and Reproductive Medicine
Keywords
- cytoplasmic and nuclear
- Receptors
- Prostatic neoplasms
- genetic
- Polymorphism
- male
- Infertility
- Hypogonadism
- Genetic association studies
- Case–control studies
- Androgens
Status
Published
Research group
- Molecular genetic reproductive medicine, Malmö
Supervisor
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-86871-67-3
Defence date
27 January 2012
Defence time
09:00
Defence place
Jubileumsaulan, Entrance 59, Skåne University Hospital Malmö
Opponent
- Jan-Erik Damber (Prof.)