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- Ruhayel, Yasir, et al.
(författare)
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Male infertility and prostate cancer risk: a nested case-control study.
- 2010
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; Jul 1, s. 1635-1643
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Tidskriftsartikel (refereegranskat)abstract
- The pathogenesis of prostate cancer is unclear, although experimental evidence implicates androgens as playing an important role. Infertile men frequently suffer from some degree of hypogonadism and may hence be hypothesized to be at lower risk of developing prostate cancer than fertile men. To test this hypothesis, we conducted a case-control study nested within "the Malmö Diet and Cancer Study" cohort in Sweden, inviting 661 prostate cancer cases and 661 age-matched controls to participate. Of the 975 (74%) respondents, we excluded 84 childless men with unknown fertility status. Thus, 891 men were included, providing 445 prostate cancer cases and 446 controls. Of these, 841 (94%) men were biological fathers and 50 (6%) men were infertile. Logistic regression showed that the infertile men were at significantly lower risk of being diagnosed with prostate cancer than the fertile men (odds ratio, 0.45; 95% confidence interval, 0.25-0.83). Conditional and unconditional multivariate models, adjusting for socioeconomic, anthropometric, and health-status-related factors, provided similar estimates. We conclude that enduring male infertility is associated with a reduced prostate cancer risk, thus corroborating the theory that normal testicular function, and hence most probably sufficient steroidogenesis, is an important contributing factor to the later development of this malignancy.
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| 2. |
- Ruhayel, Yasir
(författare)
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Male Subfertility and Prostate Cancer Risk: Epidemiological and Genetic Studies
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Androgen action plays a pivotal role in male reproductive tract physiology and pathology. The androgen receptor (AR) gene harbors two codon repeat tracts: the CAG and GGN repeats, encoding corresponding amino acid sequences of variable length; the polyglutamine and polyglycine stretches, respectively. Variation in CAG repeat length had been associated with a number of andrological disorders, whereas very little was known about the GGN repeat when the work for this thesis was started. We hypothesized that variation in GGN length may modulate AR activity, and hence the individual susceptibility to male reproductive tract disorders. We also assessed the relationship between male subfertility-dependent childlessness and prostate cancer (PCa) risk in a nested case-control study to test the hypothesis that subfertile men are at lower risk of developing PCa than fertile men, since they are frequently hypogonadal secondary to testicular dysfunction. 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.
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