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Lower prostate cancer risk in Swedish men with the androgen receptor E213 A-allele

Bentmar Holgersson, Magdalena LU ; Ruhayel, Yasir LU ; Karlsson, Magnus LU ; Giwercman, Aleksander LU ; Bjartell, Anders LU ; Ohlsson, Claes ; Mellström, Dan ; Ljunggren, Östen ; Haghsheno, Mohammad-Ali and Damber, Jan-Erik , et al. (2017) In Cancer Causes and Control 28(3). p.227-233
Abstract

Background: In a previous population-based study on 3369 European men with self-reported prostate cancer (PCa), it was shown that androgen receptor (AR) haplotype designated H2 was associated with high levels of serum PSA (prostate-specific antigen) concentration, and, at the same time, with low risk for PCa. The aim of this study was to replicate this finding in other cohorts, with registry-based cancer diagnosis. Methods: Using data from two population-based cohorts; the Malmö Diet and Cancer Study (MDCS, n = 12,121) and the Swedish Osteoporotic fractures in men study (MrOS, n = 1,120), 628 men with PCa and 1,374 controls were identified and genotyped. PCa data were collected from the Swedish national cancer registry. PCa odds ratios... (More)

Background: In a previous population-based study on 3369 European men with self-reported prostate cancer (PCa), it was shown that androgen receptor (AR) haplotype designated H2 was associated with high levels of serum PSA (prostate-specific antigen) concentration, and, at the same time, with low risk for PCa. The aim of this study was to replicate this finding in other cohorts, with registry-based cancer diagnosis. Methods: Using data from two population-based cohorts; the Malmö Diet and Cancer Study (MDCS, n = 12,121) and the Swedish Osteoporotic fractures in men study (MrOS, n = 1,120), 628 men with PCa and 1,374 controls were identified and genotyped. PCa data were collected from the Swedish national cancer registry. PCa odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for carriers of the particular AR haplotype, tagged by the rs6624304 T-allele. Results: The 15% of men who were carriers of the AR haplotype H2 had approximately one-third lower risk for PCa diagnosis compared to those with the most common H1 variant (OR 0.65; 95% CI 0.45–0.94; p = 0.021). The same trend, although not statistically significant (OR 0.75; 95% CI 0.47–1.24; p = 0.275), was observed in MrOS Sweden. When both cohorts were merged, an even more significant result was observed (OR 0.68; 95% CI 0.51–0.90; p = 0.008). Conclusions: Swedish men with the variant AR haplotype H2, tagged by rs6624304, have significantly lower risk of PCa compared to those with the more common variant.

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@article{f00fbcbf-624c-42b4-a209-e54e2c002941,
  abstract     = {{<p>Background: In a previous population-based study on 3369 European men with self-reported prostate cancer (PCa), it was shown that androgen receptor (AR) haplotype designated H2 was associated with high levels of serum PSA (prostate-specific antigen) concentration, and, at the same time, with low risk for PCa. The aim of this study was to replicate this finding in other cohorts, with registry-based cancer diagnosis. Methods: Using data from two population-based cohorts; the Malmö Diet and Cancer Study (MDCS, n = 12,121) and the Swedish Osteoporotic fractures in men study (MrOS, n = 1,120), 628 men with PCa and 1,374 controls were identified and genotyped. PCa data were collected from the Swedish national cancer registry. PCa odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for carriers of the particular AR haplotype, tagged by the rs6624304 T-allele. Results: The 15% of men who were carriers of the AR haplotype H2 had approximately one-third lower risk for PCa diagnosis compared to those with the most common H1 variant (OR 0.65; 95% CI 0.45–0.94; p = 0.021). The same trend, although not statistically significant (OR 0.75; 95% CI 0.47–1.24; p = 0.275), was observed in MrOS Sweden. When both cohorts were merged, an even more significant result was observed (OR 0.68; 95% CI 0.51–0.90; p = 0.008). Conclusions: Swedish men with the variant AR haplotype H2, tagged by rs6624304, have significantly lower risk of PCa compared to those with the more common variant.</p>}},
  author       = {{Bentmar Holgersson, Magdalena and Ruhayel, Yasir and Karlsson, Magnus and Giwercman, Aleksander and Bjartell, Anders and Ohlsson, Claes and Mellström, Dan and Ljunggren, Östen and Haghsheno, Mohammad-Ali and Damber, Jan-Erik and Giwercman, Yvonne}},
  issn         = {{0957-5243}},
  keywords     = {{Androgen receptor; Genetic variants; Prostate cancer}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{227--233}},
  publisher    = {{Springer}},
  series       = {{Cancer Causes and Control}},
  title        = {{Lower prostate cancer risk in Swedish men with the androgen receptor E213 A-allele}},
  url          = {{http://dx.doi.org/10.1007/s10552-017-0859-1}},
  doi          = {{10.1007/s10552-017-0859-1}},
  volume       = {{28}},
  year         = {{2017}},
}