Increased risk of breast cancer in individuals carrying the TNRC9 rs3803662 C>T polymorphism: a meta-analysis of case-control studies

Abstract

ABSTRACT. Currently, the relationship between the trinucleotide repeat containing 9 (TNRC9) rs3803662 C>T polymorphism and risk of breast cancer (BC) is uncertain. Here, we attempted to obtain a more accurate assessment of this association by conducting a meta-analysis of all eligible case-control investigations, comprising 44,820 cases and 58,316 controls. A comprehensive search was performed to identify all suitable studies involving the TNRC9 rs3803662 polymorphism and BC risk. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated using fixed-or random-effect models. Heterogeneity, publication bias, and sensitivity analyses were also carried out. We found that the variant T allele of rs3803662 C>T greatly increases BC risk (CT vs CC: OR = 1.14, 95%CI = 1.07-1.22, P < 0.001; TT vs CC: OR = 1.38, 95%CI = 1.25-1.53, P < 0.001; CT/TT vs CC: OR = 1.19, 95%CI = 1.11-1.28, P < 0.001; TT vs CT/CC: OR = 1.28, 95%CI = 1.19-1.38, P < 0.001). Stratified analysis based on ethnicity also revealed a markedly increased risk in Asian and Caucasian populations. Moreover, studies with hospital-based control groups showed elevated risk under the four genetic models employed, as did those using population-based controls, except under heterozygote comparison. The TNRC9 rs3803662 C>T polymorphism is greatly related to increased risk of BC, in both Asian and Caucasian populations.

Two polymorphisms, rs2046210 and rs3803662, are associated with breast cancer risk in a Vietnamese case-control cohort

“…The two remaining SNPs, rs2046210 and rs3803662, were found to be associated with breast cancer risk in our Vietnamese cohort, with P values less than 0.007 (Table 6). In addition, these results correlate with other association studies of rs2046210 and rs3803662 in Europeans and Asians, especially Japanese, with P values less than 0.03 and the highest OR (95% CI) being 2.16 (1.32-3.59) (Cai et al, 2011;Mizoo et al, 2013;Mazhar et al, 2016;Wang et al, 2016;Hu et al, 2017). Therefore, these two SNPs are likely to increase the risk of breast cancer up to two-fold in Vietnamese women (Tables 7 and 8), as in other ethnic groups.…”

“…In addition to these association studies, many metaanalyses have been conducted to increase statistical power, to resolve conflicting results between individual studies, and to improve estimates of the size of the effect (Hunter and Schmidt, 1990). The results have demonstrated consistency, with all seven SNPs shown to be significantly associated with an increased risk of breast cancer among different ethnic groups, including Asians and Europeans, with P values lower than 0.03 and OR (95% CI) values ranging from 1.07 (1.01 -1.13) to 1.62 (1.44 -1.83) (Wang et al, 2013;Zheng et al, 2014;Tang et al, 2016;Wang et al, 2016;Yang et al, 2016;Zhang et al, 2016;Hu et al, 2017). Interestingly, two SNPs, rs889312 and rs13281615, were shown not to be associated with breast cancer risk in Africans (Zheng et al, 2014;Zhang et al, 2016).…”

Association between the TOX3 rs3803662 C>T polymorphism and recurrent miscarriage in a southern Chinese population

“…20 Moreover, studies have confirmed that TOX3 methylation abnormalities may be closely related to the occurrence of PCOS and may play a role in the development of PCOS pathology by regulating changes in TOX3 protein expression. 20,22 The SNP rs3803662 C>T also shows significant associations with estrogen receptor status, 23 and patients with PCOS have a higher risk of spontaneous abortion. 20,22 The SNP rs3803662 C>T also shows significant associations with estrogen receptor status, 23 and patients with PCOS have a higher risk of spontaneous abortion.…”

“…12 Studies have shown that the genetic variants in the TOX3 gene are associated with multiple diseases, including lung cancer, familial ovarian cancer, polycystic ovary syndrome (PCOS), and breast cancer, [13][14][15][16][17][18][19] and Wang Q et al found that the rs3803662 C>T polymorphism is strongly related to an increased risk of breast cancer in both Asian and Caucasian populations. 20 Moreover, studies have confirmed that TOX3 methylation abnormalities may be closely related to the occurrence of PCOS and may play a role in the development of PCOS pathology by regulating changes in TOX3 protein expression. 21 In recent years, studies have confirmed that rs3803662 C>T is the most important genetic variation in the TOX3 locus, which is associated with an increased risk of breast cancer in women.…”

“…21 In recent years, studies have confirmed that rs3803662 C>T is the most important genetic variation in the TOX3 locus, which is associated with an increased risk of breast cancer in women. 20,22 The SNP rs3803662 C>T also shows significant associations with estrogen receptor status, 23 and patients with PCOS have a higher risk of spontaneous abortion. 24 Additionally, reproductive factors such as abortion are known risk factors for breast cancer.…”