Association of PALB2 sequence variants with the risk of familial and early-onset breast cancer in a South-American population

作者：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; Ibanez Gladys; Pakomio Janara; Grau Gilberto; Jara Lilian^*

来源：BMC Cancer, 2015, 15(1): 30.

DOI：10.1186/s12885-015-1033-3

• Familial breast cancer
• PALB2
• BRCA1/2-negative families
• South-American population

Background: 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.
Methods: 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.
Results: 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).
Conclusion: 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.

• 出版日期2015-1-31