Leyton Yessica, Gonzalez-Hormazabal Patricio, Blanco Rafael, Bravo Teresa, Fernandez-Ramires Ricardo, Morales Sebastian, Landeros Natalia, Reyes Jose M, Peralta Octavio, Tapia Julio C, Gomez Fernando, Waugh Enrique, Ibañez Gladys, Pakomio Janara, Grau Gilberto, Jara Lilian
Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile.
National Cancer Society (Corporación Nacional del Cáncer -CONAC-), Santiago, Chile.
BMC Cancer. 2015 Jan 31;15:30. doi: 10.1186/s12885-015-1033-3.
Germline mutations in PALB2 have been identified in approximately 1% of familial breast cancer (BC) in several populations. Nevertheless its contribution in the South-American population is unknown. The goal of this study was to determine the prevalence of PALB2 mutations in the Chilean population.
100 Chilean BRCA1/2-negatives familial BC cases were included for the PALB2 mutation analysis. We use conformational sensitive gel electrophoresis and direct sequencing. Using a case-control design, we studied the identified variants in 436 BC cases and 809 controls to evaluate their possible association with BC risk.
No pathogenic mutations were detected. We identified three variants, the variant c.1861C > A not previously described was found in one of the 436 cases and none of the 809 controls. The bioinformatic analyses indicate that this variant probably is not pathogenic. PALB2 c.1676A > G (rs152451A/G) and c.2993C > T (rs45551636C/T) variants were significantly associated with increased BC risk only in cases with a strong family history of BC (OR = 1.9 [CI 95% 1.3-2.8] p < 0.01 and OR = 3.3 [CI 95% 1.4-7.3] p < 0.01, respectively). The rs152451A/G-rs45551636C/T composite genotype produce increase of the BC risk in cases with a strong family history of BC (OR = 3.6 [CI 95% 1.7-8.0] p = 0.003). The rs152451-G/rs45551636-C and rs152451-G/rs45551636-T haplotypes were associated with an increased BC risk only in cases with a strong family history of BC (OR = 1.6 [CI 95% 1.0-2.5] p = 0.05 and OR = 3.7 [CI 95% 1.8-7.5] p < 0.001, respectively).
Our results suggest that PALB2 c.1676A > G and c.2993C > T play roles in BC risk in women with a strong family history of BC.
在几个人群中，约1%的家族性乳腺癌（BC）中已鉴定出PALB2的胚系突变。然而，其在南美人群中的作用尚不清楚。本研究的目的是确定智利人群中PALB2突变的患病率。
纳入100例智利BRCA1/2阴性的家族性BC病例进行PALB2突变分析。我们使用构象敏感凝胶电泳和直接测序。采用病例对照设计，我们在436例BC病例和809例对照中研究了鉴定出的变异，以评估它们与BC风险的可能关联。
未检测到致病突变。我们鉴定出三个变异，在436例病例中的1例中发现了此前未描述的变异c.1861C＞A，而809例对照中均未发现。生物信息学分析表明该变异可能不具有致病性。PALB2 c.1676A＞G（rs152451A/G）和c.2993C＞T（rs45551636C/T）变异仅在有强烈BC家族史的病例中与BC风险增加显著相关（OR分别为1.9 [95%CI 1.3 - 2.8]，p＜0.01和OR为3.3 [95%CI 1.4 - 7.3]，p＜0.01）。rs152451A/G - rs45551636C/T复合基因型在有强烈BC家族史的病例中导致BC风险增加（OR = 3.6 [95%CI 1.7 - 8.0]，p = 0.003）。rs152451 - G/rs45551636 - C和rs152451 - G/rs45551636 - T单倍型仅在有强烈BC家族史的病例中与BC风险增加相关（OR分别为1.6 [95%CI 1.0 - 2.5]，p = 0.05和OR为3.7 [95%CI 1.8 - 7.5]，p＜0.001）。
我们的结果表明，PALB2 c.1676A＞G和c.2993C＞T在有强烈BC家族史的女性的BC风险中起作用。
