rs12255372

rs12255372, also known as IVS4G>T and c.483+9017G>T, is a well-studied SNP in the TCF7L2 gene on chromosome 10. In some studies, it has been linked to slight increases in risk for type-2 diabetes, breast cancer and aggressive prostate cancer. * Type-2 Diabetes Risk Overview: numerous papers report an increase in risk, on the order of 1.5 - 2x for the risk genotypes compared to the non-risk genotype. Key papers include: ** reports the association of rs12255372 and rs7903146 with Type-2 diabetes in a Finnish sample. **rs12255372 Common variants (rs12255372 and rs7903146) in TCF7L2 seem to be associated with an increased risk of diabetes among persons with impaired glucose tolerance ** Considered for type-2 diabetes with rs7903146 rs12255372 rs10885406. ** Associated in a study of ~1000 Hispanic-Americans with reduced insulin secretion as measured by acute insulin response and adjusted for the degree of insulin sensitivity (p = 0.036). ** This SNP was confirmed to be associated with type-2 diabetes in a study of 500+ Japanese patients plus pooled meta-analysis with 6 previous association studies (also of Japanese). **A HuGE review and meta-analysis including over 35,000 type-2 diabetes cases and 39,000 controls concluded that the Bayesian odds ratio for rs12255372(T;T) homozygotes and (G;T) heterozygotes versus (G;G) homozygotes was 1.885 (95% credible interval (CrI): 1.698 - 2.088) and 1.360 (95% CrI: 1.291 - 1.433), respectively. Along with 3 other TCF7L2 SNPs, a multiplicative genetic model was indicated. * Breast Cancer Risk Overview: some papers report a small increase in risk, around 1.1 to 1.2x for the risk genotypes compared to the non-risk genotype, and other papers report no increased risk. Key papers include: ** is the paper which links it to Breast cancer. It suggests the T allele as increasing risk. ** Meta-analysis totaling 4800 breast cancer cases finds a small risk increase (1.07 to 1.17x, depending on genetic model) for T allele ** Mayo Clinic study of 800 patients found no association between rs12255372 and risk for breast cancer or ovarian cancer ** A study of 7,700 Hispanic patients did find increased risk for the rs12255372 T allele, however, it was of borderline statistical significance * Prostate Cancer Risk Overview: ** In a study of 1,457 prostate cancer cases and 1,351 controls, while there was no association with overall risk, males who were rs12255372(T;T) homozygotes and who had prostate cancer were at elevated relative risk of more aggressive prostate cancer, as defined by high Gleason score (OR = 1.7, CI: 1.0-2.8) or regional/distant stage (OR = 1.7, CI: 1.1-2.6) disease. Many other papers mention rs12255372, including:

G;T

see discussion at rs12255372

T;T

see discussion at rs12255372