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The GADD45A (1506T>C) Polymorphism Is Associated with Ovarian Cancer Susceptibility and Prognosis.

Yuan C, Liu X, Liu X, Yang N, Liu Z, Yan S, Shen K, Kong B - PLoS ONE (2015)

Bottom Line: We found a statistically significant difference in the GADD45A (1506T>C) genotype distributions between the case and control groups (TT vs.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).

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Association of the GADD45A (1506T>C) genotype and GADD45A mRNA expression.A, Relative levels of GADD45A mRNA expression in ovarian cancer tissues compared to normal ovarian tissues. B, Relative levels of GADD45A mRNA expression in the ovarian cancer tissues of patients with different 1506T>C genotypes. C, Relative levels of GADD45A mRNA expression in the normal control tissues of subjects with different 1506T>C genotypes. One spot represents the mean of three independent measurements obtained from one subject. Distributions of the three genotypes were random between the groups. N represents the number of samples in each respective group. Bars represent the standard deviation. Student’s t-test was used to evaluate the differences in the expression levels of different constructs.
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pone.0138692.g002: Association of the GADD45A (1506T>C) genotype and GADD45A mRNA expression.A, Relative levels of GADD45A mRNA expression in ovarian cancer tissues compared to normal ovarian tissues. B, Relative levels of GADD45A mRNA expression in the ovarian cancer tissues of patients with different 1506T>C genotypes. C, Relative levels of GADD45A mRNA expression in the normal control tissues of subjects with different 1506T>C genotypes. One spot represents the mean of three independent measurements obtained from one subject. Distributions of the three genotypes were random between the groups. N represents the number of samples in each respective group. Bars represent the standard deviation. Student’s t-test was used to evaluate the differences in the expression levels of different constructs.

Mentions: We further tested the potential relationship between the GADD45A (1506T>C) polymorphism and GADD45A mRNA expression levels in vivo. As shown in Fig 2A, the levels of GADD45A mRNA in 22 ovarian cancer tissues were significantly lower than the levels observed in 15 normal tissues (P<0.001). As shown in Fig 2B, the GADD45A mRNA expression was higher in patients with TT or TC genotypes compared to patients with the CC genotype (P<0.001). As shown in Fig 2C, the GADD45A mRNA expression was higher in controls with TT or TC genotypes than with the CC genotype, (P<0.001). These findings suggest that the SNP 1506T>C may significantly affect the expression of the GADD45A gene.


The GADD45A (1506T>C) Polymorphism Is Associated with Ovarian Cancer Susceptibility and Prognosis.

Yuan C, Liu X, Liu X, Yang N, Liu Z, Yan S, Shen K, Kong B - PLoS ONE (2015)

Association of the GADD45A (1506T>C) genotype and GADD45A mRNA expression.A, Relative levels of GADD45A mRNA expression in ovarian cancer tissues compared to normal ovarian tissues. B, Relative levels of GADD45A mRNA expression in the ovarian cancer tissues of patients with different 1506T>C genotypes. C, Relative levels of GADD45A mRNA expression in the normal control tissues of subjects with different 1506T>C genotypes. One spot represents the mean of three independent measurements obtained from one subject. Distributions of the three genotypes were random between the groups. N represents the number of samples in each respective group. Bars represent the standard deviation. Student’s t-test was used to evaluate the differences in the expression levels of different constructs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4589388&req=5

pone.0138692.g002: Association of the GADD45A (1506T>C) genotype and GADD45A mRNA expression.A, Relative levels of GADD45A mRNA expression in ovarian cancer tissues compared to normal ovarian tissues. B, Relative levels of GADD45A mRNA expression in the ovarian cancer tissues of patients with different 1506T>C genotypes. C, Relative levels of GADD45A mRNA expression in the normal control tissues of subjects with different 1506T>C genotypes. One spot represents the mean of three independent measurements obtained from one subject. Distributions of the three genotypes were random between the groups. N represents the number of samples in each respective group. Bars represent the standard deviation. Student’s t-test was used to evaluate the differences in the expression levels of different constructs.
Mentions: We further tested the potential relationship between the GADD45A (1506T>C) polymorphism and GADD45A mRNA expression levels in vivo. As shown in Fig 2A, the levels of GADD45A mRNA in 22 ovarian cancer tissues were significantly lower than the levels observed in 15 normal tissues (P<0.001). As shown in Fig 2B, the GADD45A mRNA expression was higher in patients with TT or TC genotypes compared to patients with the CC genotype (P<0.001). As shown in Fig 2C, the GADD45A mRNA expression was higher in controls with TT or TC genotypes than with the CC genotype, (P<0.001). These findings suggest that the SNP 1506T>C may significantly affect the expression of the GADD45A gene.

Bottom Line: We found a statistically significant difference in the GADD45A (1506T>C) genotype distributions between the case and control groups (TT vs.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).

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus