Replication of genetic susceptibility loci for testicular germ cell cancer in the Croatian population.
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Replication of genetic susceptibility loci for testicular germ cell cancer in the Croatian population. / Lessel, Davor; Gamulin, Marija; Kulis, Tomislav; Toliat, Mohammad Reza; Grgic, Mislav; Friedrich, Katrin; Zunec, Renata; Balija, Melita; Nürnberg, Peter; Kastelan, Zeljko; Högel, Josef; Kubisch, Christian.
in: CARCINOGENESIS, Jahrgang 33, Nr. 8, 8, 2012, S. 1548-1552.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Replication of genetic susceptibility loci for testicular germ cell cancer in the Croatian population.
AU - Lessel, Davor
AU - Gamulin, Marija
AU - Kulis, Tomislav
AU - Toliat, Mohammad Reza
AU - Grgic, Mislav
AU - Friedrich, Katrin
AU - Zunec, Renata
AU - Balija, Melita
AU - Nürnberg, Peter
AU - Kastelan, Zeljko
AU - Högel, Josef
AU - Kubisch, Christian
PY - 2012
Y1 - 2012
N2 - Genome-wide association studies in patients with testicular germ-cell tumors (TGCT) from Great Britain and the United States have identified six susceptibility loci in or near biologically plausible candidate genes. However, these loci have not been replicated in an independent European sample. We performed a genetic replication study of previously identified TGCT susceptibility loci in a Croatian case-control sample and performed additional analyses as concerning histological subtypes or tumor staging. We analyzed six single-nucleotide polymorphisms [rs2900333 (ATF7IP), rs210138 (BAK1), rs755383 (DMRT1), rs995030 (KITLG), rs4624820 (SPRY4), and rs4635969 (TERT/CLPTM1L)], each representing one of the published susceptibility loci/genes. Five susceptibility loci were found to be also associated in the Croatian population with P-values between 2.1e-10 (rs995030; odds ratio [OR] 3.08) and 0.01739 (rs4635969; OR 1.37), which remained statistically significant after correction for multiple testing. Although rs2900333 near ATF7IP just showed borderline association with all-TGCT (OR 1.24, P = 0.062), it showed significant association with the more aggressive forms of the tumor (OR 1.51, P = 0.0067)-a clinically interesting finding, which however has to be replicated in an independent sample. Assessment of cumulative risks revealed that men with at least seven risk alleles have a more than 2.5-fold increased disease risk (OR = 2.73, 95% confidence interval = 1.98-3.79). In summary, we independently replicated the majority of TGCT susceptibility loci identified previously in a Croatian sample and suggested a possible role of genetic variation near ATF7IP in regulating disease progression.
AB - Genome-wide association studies in patients with testicular germ-cell tumors (TGCT) from Great Britain and the United States have identified six susceptibility loci in or near biologically plausible candidate genes. However, these loci have not been replicated in an independent European sample. We performed a genetic replication study of previously identified TGCT susceptibility loci in a Croatian case-control sample and performed additional analyses as concerning histological subtypes or tumor staging. We analyzed six single-nucleotide polymorphisms [rs2900333 (ATF7IP), rs210138 (BAK1), rs755383 (DMRT1), rs995030 (KITLG), rs4624820 (SPRY4), and rs4635969 (TERT/CLPTM1L)], each representing one of the published susceptibility loci/genes. Five susceptibility loci were found to be also associated in the Croatian population with P-values between 2.1e-10 (rs995030; odds ratio [OR] 3.08) and 0.01739 (rs4635969; OR 1.37), which remained statistically significant after correction for multiple testing. Although rs2900333 near ATF7IP just showed borderline association with all-TGCT (OR 1.24, P = 0.062), it showed significant association with the more aggressive forms of the tumor (OR 1.51, P = 0.0067)-a clinically interesting finding, which however has to be replicated in an independent sample. Assessment of cumulative risks revealed that men with at least seven risk alleles have a more than 2.5-fold increased disease risk (OR = 2.73, 95% confidence interval = 1.98-3.79). In summary, we independently replicated the majority of TGCT susceptibility loci identified previously in a Croatian sample and suggested a possible role of genetic variation near ATF7IP in regulating disease progression.
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Middle Aged
KW - Adolescent
KW - Case-Control Studies
KW - Genetic Predisposition to Disease
KW - Croatia
KW - Neoplasms, Germ Cell and Embryonal/genetics
KW - Testicular Neoplasms/genetics
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Middle Aged
KW - Adolescent
KW - Case-Control Studies
KW - Genetic Predisposition to Disease
KW - Croatia
KW - Neoplasms, Germ Cell and Embryonal/genetics
KW - Testicular Neoplasms/genetics
M3 - SCORING: Journal article
VL - 33
SP - 1548
EP - 1552
JO - CARCINOGENESIS
JF - CARCINOGENESIS
SN - 0143-3334
IS - 8
M1 - 8
ER -
