Background There is strong evidence that genetic variation influences the risk of testicular germ cell tumor (TGCT). The oncogene AKT1, tumor suppressor gene PTEN and the 8q24 locus play important roles in cancer development, and investigation of their role in TGCT is warranted.

Methods We investigated the association between risk of TGCT and genetic variation in the AKT1 and PTEN genes, and the 8q24 locus in a Norwegian-Swedish case-parent study. We included 831 triads, 474 dyads and 712 singletons, and 26 single nucleotide polymorphisms (SNPs) were genotyped. First, triads and dyads were included in a likelihood-based association test. To increase the statistical power, case singletons and 3922 unrelated controls from the Swedish TwinGene project were included in a single test for association. Interaction terms were included in the statistical model to examine if the allelic effect on TGCT risk was modified by histological subgroup, country of origin or parent of origin. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated and Bonferroni correction (Pbonf) was used to adjust for multiple testing.

Results In the case-parent triad analyses, none of the 26 SNPs were significantly associated with TGCT. Of the 23 SNPs investigated in the combined study, one SNP in the PTEN gene, the rs11202586, remained associated with TGCT risk after adjusting for multiple testing (OR=1.16, 95% CI=1.06-1.28, Pbonf=0.040). We found no difference in risk according to histological subgroup, parent of origin or between countries.

Conclusions Our findings suggest that genetic variation in the PTEN gene influences the risk of TGCT.

Table. Odds ratios (ORs) for associations between polymorphisms in AKT1, PTEN and 8q24 locus and TGCT risk in the combined case-parent/case-control study.

GeneGene nameSNPAllele1*Allele2Genomic positionCHROR95% CIPPbonf#
AKT1 v-akt murine thymoma viral oncogene homolog 1 rs2494731 104308725 14 0.93 0.86–1.01 0.071 1.000 
  rs2494739 104318034  0.96 0.83–1.11 0.594 1.000 
  rs2494752 104334653  0.95 0.81–1.11 0.502 1.000 
  rs4983387 104339273  1.07 0.95–1.22 0.283 1.000 
PTEN phosphatase and tensin homolog rs1234212 89598872 10 0.99 0.92–1.07 0.824 1.000 
  rs11202586 89602004  1.16 1.06–1.28 0.002 0.040 
  rs1234221 89606459  0.97 0.89–1.06 0.537 1.000 
  rs1234220 89635453  1.16 1.03–1.31 0.018 0.414 
  rs1234219 89639557  1.09 0.95–1.25 0.221 1.000 
  rs2299939 89647130  1.04 0.95–1.15 0.386 1.000 
  rs12357281 89690651  1.05 0.91–1.20 0.534 1.000 
  rs2248293 89697245  0.95 0.88–1.03 0.233 1.000 
  rs926091 89711392  0.91 0.82–1.02 0.105 1.000 
8q24 locus  rs7008482 126336812 0.91 0.84–0.99 0.029 0.674 
  rs13254738 128173525  1.02 0.94–1.10 0.707 1.000 
  rs6983561 128176062  0.98 0.80–1.19 0.815 1.000 
  rs16901979 128194098  0.94 0.78–1.15 0.566 1.000 
  rs6983267 128482487  0.98 0.91–1.05 0.548 1.000 
  rs7000448 128510352  0.97 0.90–1.05 0.424 1.000 
  rs1447295 128554220  0.99 0.88–1.11 0.864 1.000 
  rs4242382 128586755  1.00 0.89–1.13 0.986 1.000 
  rs7017300 128594450  0.94 0.85–1.05 0.266 1.000 
  rs7837688 128608542  1.06 0.94–1.19 0.333 1.000 
GeneGene nameSNPAllele1*Allele2Genomic positionCHROR95% CIPPbonf#
AKT1 v-akt murine thymoma viral oncogene homolog 1 rs2494731 104308725 14 0.93 0.86–1.01 0.071 1.000 
  rs2494739 104318034  0.96 0.83–1.11 0.594 1.000 
  rs2494752 104334653  0.95 0.81–1.11 0.502 1.000 
  rs4983387 104339273  1.07 0.95–1.22 0.283 1.000 
PTEN phosphatase and tensin homolog rs1234212 89598872 10 0.99 0.92–1.07 0.824 1.000 
  rs11202586 89602004  1.16 1.06–1.28 0.002 0.040 
  rs1234221 89606459  0.97 0.89–1.06 0.537 1.000 
  rs1234220 89635453  1.16 1.03–1.31 0.018 0.414 
  rs1234219 89639557  1.09 0.95–1.25 0.221 1.000 
  rs2299939 89647130  1.04 0.95–1.15 0.386 1.000 
  rs12357281 89690651  1.05 0.91–1.20 0.534 1.000 
  rs2248293 89697245  0.95 0.88–1.03 0.233 1.000 
  rs926091 89711392  0.91 0.82–1.02 0.105 1.000 
8q24 locus  rs7008482 126336812 0.91 0.84–0.99 0.029 0.674 
  rs13254738 128173525  1.02 0.94–1.10 0.707 1.000 
  rs6983561 128176062  0.98 0.80–1.19 0.815 1.000 
  rs16901979 128194098  0.94 0.78–1.15 0.566 1.000 
  rs6983267 128482487  0.98 0.91–1.05 0.548 1.000 
  rs7000448 128510352  0.97 0.90–1.05 0.424 1.000 
  rs1447295 128554220  0.99 0.88–1.11 0.864 1.000 
  rs4242382 128586755  1.00 0.89–1.13 0.986 1.000 
  rs7017300 128594450  0.94 0.85–1.05 0.266 1.000 
  rs7837688 128608542  1.06 0.94–1.19 0.333 1.000 

* Reference allele

# Bonferroni correction (P multiplied by the number of total SNPs analyses, n = 23).

Citation Format: Kristine E. Andreassen, Wenche Kristiansen, Robert Karlsson, Elin L. Aschim, Olav Dahl, Sophie D. Fosså, Hans-Olov Adami, Fredrik Wiklund, Trine B. Haugen, Tom Grotmol. Association between genetic variation at the AKT1 and PTEN genes, and in the 8q24 locus, and the risk of testicular germ cell tumor. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1348. doi:10.1158/1538-7445.AM2013-1348