That no individual studies significantly affected the pooled ORs

That no individual studies significantly affected the pooled ORs 1379592 under any genetic models of PvuII (C.T) and XbaI (A.G) polymorphisms (Figure 3), indicating a statistically robust result. Publication biases within available research results might not be representative of all research results. Begger’s funnel plot and Egger’s linear regression test were performed to assess the publication biases of included studies. The shapes of the funnel plots did not reveal any evidence of obvious asymmetry under the dominant model of PvuII (C.T) and XbaI (A.G) polymorphisms (Figure 4). Egger’s test also showed that there was no strong statistical evidence of publication bias (PvuII: t = 21.31, P = 0.232; XbaI: t = 20.73, P = 0.496).DiscussionESR1 gene is critical for hormone binding, DNA binding, and activation of transcription because it encodes an estrogen receptor that is key in the mediation of hormonal response in estrogensensitive tissues [24]. Thus, genetic mutations in ESR1 gene may contribute to its abnormal expression and are probably linked to increased risk of hormone-related cancers such as the breast, prostate, and SIS3 site endometrial cancers [28]. Li et al performed a metaanalysis that evaluated the association between ESR1 gene polymorphisms and breast Calcitonin (salmon) cancer risk in diverse populations [29]. There results suggests that variant genotypes of PvuII and rs1801132 (Codon 325) may contribute to breast cancer susceptibility. Several ESR1 gene polymorphisms have been identified as candidates for prostate cancer susceptibility and among these, ESR1 PvuII and XbaI SNPs were suggested to possess significant associations with the development of prostate cancer [30]. Many previous genetic studies have suggested that ESR1 gene polymorphisms may play an important role in endometrial carcinogenesis [17?9,22,24,25,27], while other studies found no convincing evidence of these polymorphisms in increasing endometrial cancer susceptibility [7,8,21,23,26]. This controversy could be explained with several reasons, including the differences in study designs, sample size, ethnicity, statistical methods, etc. A recent meta-analysis by Wang et al indicated that PvuII polymorphism in the ESR1 gene could increase the risk of endometrial cancer, while XbaI polymorphism was not associated with susceptibility to endometrial cancer. However, they failed to assess the relationship between the other common polymorphisms in the ESR1 gene and endometrial cancer risk. This recent meta-analysis is aimed to update previous meta-analysis, as well as to provide a more comprehensive and reliable conclusion on the associations between eight common functional polymorphisms in the ESR1 gene and endometrial cancer susceptibility.In this meta-analysis, 13 independent case-control studies were included with a total of 7,649 endometrial cancer cases and 16,855 healthy controls. When all the eligible studies were pooled into the meta-analysis, the results showed that PvuII (C.T) polymorphism was associated with increased risk of endometrial cancer, especially among Caucasian populations, while similar associations were not observed among Asian populations. Although the exact function of PvuII (C.T) polymorphism in the development of endometrial cancer among different populations is not yet clear, a possible reason could be that inherited mutations in ESR1 might be associated with changes in estrogen metabolism and thereby could possibly explain inter-individual differences in disease incid.That no individual studies significantly affected the pooled ORs 1379592 under any genetic models of PvuII (C.T) and XbaI (A.G) polymorphisms (Figure 3), indicating a statistically robust result. Publication biases within available research results might not be representative of all research results. Begger’s funnel plot and Egger’s linear regression test were performed to assess the publication biases of included studies. The shapes of the funnel plots did not reveal any evidence of obvious asymmetry under the dominant model of PvuII (C.T) and XbaI (A.G) polymorphisms (Figure 4). Egger’s test also showed that there was no strong statistical evidence of publication bias (PvuII: t = 21.31, P = 0.232; XbaI: t = 20.73, P = 0.496).DiscussionESR1 gene is critical for hormone binding, DNA binding, and activation of transcription because it encodes an estrogen receptor that is key in the mediation of hormonal response in estrogensensitive tissues [24]. Thus, genetic mutations in ESR1 gene may contribute to its abnormal expression and are probably linked to increased risk of hormone-related cancers such as the breast, prostate, and endometrial cancers [28]. Li et al performed a metaanalysis that evaluated the association between ESR1 gene polymorphisms and breast cancer risk in diverse populations [29]. There results suggests that variant genotypes of PvuII and rs1801132 (Codon 325) may contribute to breast cancer susceptibility. Several ESR1 gene polymorphisms have been identified as candidates for prostate cancer susceptibility and among these, ESR1 PvuII and XbaI SNPs were suggested to possess significant associations with the development of prostate cancer [30]. Many previous genetic studies have suggested that ESR1 gene polymorphisms may play an important role in endometrial carcinogenesis [17?9,22,24,25,27], while other studies found no convincing evidence of these polymorphisms in increasing endometrial cancer susceptibility [7,8,21,23,26]. This controversy could be explained with several reasons, including the differences in study designs, sample size, ethnicity, statistical methods, etc. A recent meta-analysis by Wang et al indicated that PvuII polymorphism in the ESR1 gene could increase the risk of endometrial cancer, while XbaI polymorphism was not associated with susceptibility to endometrial cancer. However, they failed to assess the relationship between the other common polymorphisms in the ESR1 gene and endometrial cancer risk. This recent meta-analysis is aimed to update previous meta-analysis, as well as to provide a more comprehensive and reliable conclusion on the associations between eight common functional polymorphisms in the ESR1 gene and endometrial cancer susceptibility.In this meta-analysis, 13 independent case-control studies were included with a total of 7,649 endometrial cancer cases and 16,855 healthy controls. When all the eligible studies were pooled into the meta-analysis, the results showed that PvuII (C.T) polymorphism was associated with increased risk of endometrial cancer, especially among Caucasian populations, while similar associations were not observed among Asian populations. Although the exact function of PvuII (C.T) polymorphism in the development of endometrial cancer among different populations is not yet clear, a possible reason could be that inherited mutations in ESR1 might be associated with changes in estrogen metabolism and thereby could possibly explain inter-individual differences in disease incid.