TY - JOUR
T1 - Common variation in nemo-like kinase is associated with risk of ovarian cancer
AU - Stevens, Kristen N.
AU - Kelemen, Linda E.
AU - Wang, Xianshu
AU - Fridley, Brooke L.
AU - Vierkant, Robert A.
AU - Fredericksen, Zachary
AU - Armasu, Sebastian M.
AU - Tsai, Ya Yu
AU - Berchuck, Andrew
AU - Narod, Steven A.
AU - Phelan, Catherine M.
AU - Sutphen, Rebecca
AU - Birrer, Michael J.
AU - Schildkraut, Joellen M.
AU - Sellers, Thomas A.
AU - Goode, Ellen L.
AU - Couch, Fergus J.
PY - 2012/3
Y1 - 2012/3
N2 - Background: Overexpression of mitotic kinases has been associated with prognosis, histologic grade, and clinical stage in ovarian cancer, but the relationship between inherited variation in these genes and ovarian cancer risk has not been well defined. Methods: We measured associations between 397 single nucleotide polymorphisms (SNPs) from 67 mitotic kinases and invasive epithelial ovarian cancer risk in two case-control studies (n = 671 cases; n = 939 controls). Thirty-six candidate SNPs (P < 0.05) were assessed in a replication analysis consisting of three additional studies (n = 1,094 cases; n = 829 controls). Results: In initial analysis, thirty-six SNPs were suggestive of association with risk of serous ovarian cancer, all subtypes of ovarian cancer, or both (P < 0.05). Replication analyses suggested an association between rs2125846 in the Nemo-like kinase (NLK) gene and ovarian cancer (serous OR = 1.36, 95% CI: 1.11-1.67, P = 1.77 × 10 -3; all subtypes OR = 1.30, 95% CI: 1.08-1.56, P = 2.97 < 10 -3). Furthermore, rs2125846 was associated with risk in the combined discovery and replication sets (serous OR = 1.33, 95% CI: 1.15-1.54; all subtypes OR = 1.27, 95% CI: 1.12-1.45). Conclusions: Variation in NLK may be associated with risk of invasive epithelial ovarian cancer. Further studies are needed to confirm and understand the biologic relationship between this mitotic kinase and ovarian cancer risk. Impact: An association between SNPs in NLK and ovarian cancer may provide biologic insight into the development of this disease.
AB - Background: Overexpression of mitotic kinases has been associated with prognosis, histologic grade, and clinical stage in ovarian cancer, but the relationship between inherited variation in these genes and ovarian cancer risk has not been well defined. Methods: We measured associations between 397 single nucleotide polymorphisms (SNPs) from 67 mitotic kinases and invasive epithelial ovarian cancer risk in two case-control studies (n = 671 cases; n = 939 controls). Thirty-six candidate SNPs (P < 0.05) were assessed in a replication analysis consisting of three additional studies (n = 1,094 cases; n = 829 controls). Results: In initial analysis, thirty-six SNPs were suggestive of association with risk of serous ovarian cancer, all subtypes of ovarian cancer, or both (P < 0.05). Replication analyses suggested an association between rs2125846 in the Nemo-like kinase (NLK) gene and ovarian cancer (serous OR = 1.36, 95% CI: 1.11-1.67, P = 1.77 × 10 -3; all subtypes OR = 1.30, 95% CI: 1.08-1.56, P = 2.97 < 10 -3). Furthermore, rs2125846 was associated with risk in the combined discovery and replication sets (serous OR = 1.33, 95% CI: 1.15-1.54; all subtypes OR = 1.27, 95% CI: 1.12-1.45). Conclusions: Variation in NLK may be associated with risk of invasive epithelial ovarian cancer. Further studies are needed to confirm and understand the biologic relationship between this mitotic kinase and ovarian cancer risk. Impact: An association between SNPs in NLK and ovarian cancer may provide biologic insight into the development of this disease.
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U2 - 10.1158/1055-9965.EPI-11-0797
DO - 10.1158/1055-9965.EPI-11-0797
M3 - Article
C2 - 22253297
AN - SCOPUS:84859403202
SN - 1055-9965
VL - 21
SP - 523
EP - 528
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 3
ER -