title: The GADD45A (1506T>C) Polymorphism Is Associated with Ovarian Cancer Susceptibility and Prognosis.
abstract: GADD45A (growth arrest and DNA damage 45 A) is the first stress-inducible gene identified to be a target of p53. However, no studies to date have assessed variants of the GADD45 gene and their potential relationship to tumor susceptibility. We investigated the association of the GADD45A (1506T>C) polymorphism with ovarian cancer development in 258 ovarian cancer patients and 332 age-matched healthy women as controls using sequence analysis. We found a statistically significant difference in the GADD45A (1506T>C) genotype distributions between the case and control groups (TT vs. TC vs. CC, P = 0.0021) and found that variant 1506T>C was significantly associated with an increased risk of ovarian cancer (P<0.001, OR = 1.71, 95% CI [1.28-2.29]). We observed a statistically significant effect between tumor histology (P = 0.032) and CA125 status (P = 0.021). Carrying the C allele (TC+CC) was associated with an increased risk of positive CA125 (OR = 3.20, 95% CI [1.15-8.71). Carrying the T allele (TT+TC) showed a significant correlation with both higher GADD45A mRNA expression and longer ovarian cancer RFS (relapse-free survival) and OS (overall survival). We are the first group to demonstrate that the GADD45A (1506T>C) polymorphism is associated with ovarian cancer susceptibility and prognosis. These data suggest that GADD45A (1506T>C) is a new tumor susceptibility gene and could be a useful molecular marker for assessing ovarian cancer risk and for predicting ovarian cancer patient prognosis.
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China; Gynecologic Oncology Key Laboratory of Shandong Province, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China.
authors.forename: Cunzhong
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China; Gynecologic Oncology Key Laboratory of Shandong Province, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China; Gynecologic Oncology Key Laboratory of Shandong Province, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China; Gynecologic Oncology Key Laboratory of Shandong Province, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China; Gynecologic Oncology Key Laboratory of Shandong Province, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China.
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China; Gynecologic Oncology Key Laboratory of Shandong Province, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China.
authors.forename: Shi
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Keng
authors.initials: K
authors.lastname: Shen
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China; Gynecologic Oncology Key Laboratory of Shandong Province, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China.
authors.forename: Beihua
authors.initials: B
authors.lastname: Kong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D011110:Polymorphism, Genetic; D015996:Survival Rate; D000097642:GADD45 Proteins
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C439070:GADD45A protein, human; D000097642:GADD45 Proteins