Cumulative epidemiological evidence of an association was graded as strong for rs7903146 [odds ratio (OR) = 1.05, p = 4.13 × 10<sup>-5</sup> ] and rs7904519 (OR = 1.07, p = 2.02 × 10<sup>-14</sup> ) in breast cancer, rs11196172 (OR = 1.11, p = 2.22 × 10<sup>-16</sup> ), rs12241008 (OR = 1.13, p = 1.36 × 10<sup>-10</sup> ) and rs10506868 (OR = 1.10, p = 3.98 × 10<sup>-9</sup> ) in colorectal cancer, rs7086803 in lung cancer (OR = 1.30, p = 3.54 × 10<sup>-18</sup> ) and rs11196067 (OR = 1.18, p = 3.59 × 10<sup>-13</sup> ) in glioma, moderate for rs12255372 (OR = 1.12, p = 2.52 × 10<sup>-4</sup> ) in breast cancer and weak for rs7903146 (OR = 1.11, p = 0.007) in colorectal cancer.
Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p < 0.001), rs9939609 (FTO) (OR 0.94, 95 % CI = 0.92-0.95, p = 4.13E-13), rs7903146 (TCF7L2) (OR 1.04, 95 % CI = 1.02-1.06, p = 1.26E-05), and rs8042680 (PRC1) (OR 0.97, 95 % CI = 0.95-0.99, p = 8.05E-04).
This meta-analysis demonstrated that TCF7L2 gene polymorphisms (rs12255372 and rs7903146) are associated with an increased susceptibility to breast cancer.
In conclusion, our findings suggest that rs7903146 (T) variant may elevate the risk of breast cancer, thus could be a potential candidate for breast cancer susceptibility.
After adjusting for multiple comparisons, four TCF7L2 SNPs were significantly associated with breast cancer overall: rs7903146 (OR(TT) 1.24; 95 % CI 1.03-1.49), rs3750805 (OR(AT/TT) 1.15; 95 % CI 1.03-1.28), rs7900150 (OR(AA) 1.23; 95 % 1.07-1.42), and rs1225404 (OR(CC) 0.82; 95 % 0.70-0.94).