Programa de Genética Humana, Instituto de Ciencia Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, 8380453, Santiago, Chile.
Laboratorio de Transformación Celular, Programa de Biología Celular y Molecular, Facultad de Medicina, Universidad de Chile, 8380453, Santiago, Chile.
Biol Res. 2022 May 31;55(1):20. doi: 10.1186/s40659-022-00384-4.
Driver mutations are the genetic components responsible for tumor initiation and progression. These variants, which may be inherited, influence cancer risk and therefore underlie many familial cancers. The present study examines the potential association between SNPs in driver genes SF3B1 (rs4685), TBX3 (rs12366395, rs8853, and rs1061651) and MAP3K1 (rs72758040) and BC in BRCA1/2-negative Chilean families.
The SNPs were genotyped in 486 BC cases and 1258 controls by TaqMan Assay.
Our data do not support an association between rs4685:C > T, rs8853:T > C, or rs1061651:T > C and BC risk. However, the rs12366395-G allele (A/G + G/G) was associated with risk in families with a strong history of BC (OR = 1.2 [95% CI 1.0-1.6] p = 0.02 and OR = 1.5 [95% CI 1.0-2.2] p = 0.02, respectively). Moreover, rs72758040-C was associated with increased risk in cases with a moderate-to-strong family history of BC (OR = 1.3 [95% CI 1.0-1.7] p = 0.02 and OR = 1.3 [95% CI 1.0-1.8] p = 0.03 respectively). Finally, risk was significantly higher in homozygous C/C cases from families with a moderate-to-strong BC history (OR = 1.8 [95% CI 1.0-3.1] p = 0.03 and OR = 1.9 [95% CI 1.1-3.4] p = 0.01, respectively). We also evaluated the combined impact of rs12366395-G and rs72758040-C. Familial BC risk increased in a dose-dependent manner with risk allele count, reflecting an additive effect (p-trend = 0.0002).
Our study suggests that germline variants in driver genes TBX3 (rs12366395) and MAP3K1 (rs72758040) may influence BC risk in BRCA1/2-negative Chilean families. Moreover, the presence of rs12366395-G and rs72758040-C could increase BC risk in a Chilean population.
驱动基因突变是导致肿瘤发生和进展的遗传因素。这些变体可能是遗传的，会影响癌症风险，因此是许多家族性癌症的基础。本研究探讨了 SF3B1（rs4685）、TBX3（rs12366395、rs8853 和 rs1061651）和 MAP3K1（rs72758040）驱动基因中的 SNPs 与 BRCA1/2 阴性智利家族中的乳腺癌之间的潜在关联。
采用 TaqMan 分析检测 486 例乳腺癌病例和 1258 例对照的 SNPs 基因型。
我们的数据不支持 rs4685:C>T、rs8853:T>C 或 rs1061651:T>C 与乳腺癌风险之间的关联。然而，rs12366395-G 等位基因（A/G+G/G）与乳腺癌家族史较强的家族（OR=1.2[95%CI1.0-1.6]p=0.02 和 OR=1.5[95%CI1.0-2.2]p=0.02）的风险相关。此外，rs72758040-C 与乳腺癌家族史中-中度至强的病例的风险增加相关（OR=1.3[95%CI1.0-1.7]p=0.02 和 OR=1.3[95%CI1.0-1.8]p=0.03）。最后，来自中-强乳腺癌家族史的纯合子 C/C 病例的风险显著增加（OR=1.8[95%CI1.0-3.1]p=0.03 和 OR=1.9[95%CI1.1-3.4]p=0.01）。我们还评估了 rs12366395-G 和 rs72758040-C 的联合影响。乳腺癌家族史的风险随着风险等位基因数的增加而呈剂量依赖性增加，反映出相加效应（p 趋势=0.0002）。
本研究表明，TBX3（rs12366395）和 MAP3K1（rs72758040）驱动基因中的种系变异可能影响 BRCA1/2 阴性智利家族的乳腺癌风险。此外，rs12366395-G 和 rs72758040-C 的存在可能会增加智利人群的乳腺癌风险。
