Role of PALB2 Polymorphisms with Regard to Susceptibility to Female Breast Cancer Risk in the Chinese Population.

Aims: PALB2 (partner and localizer of BRCA2) is a nuclear partner of BRCA2 and promotes its localization and stability in the nucleus, allowing it to function in DNA repair and at the S-phase checkpoint. It has been hypothesized that polymorphisms in the PALB2 gene may be associated with tumorigenesis, particularly with respect to susceptibility to breast cancer.

Methods: To assess the association of polymorphisms in the PALB2 gene with breast cancer risk in a Chinese female population a total of 351 female breast cancer patients and 360 age-, gender-matched tumor-free individuals were enrolled in this case-control study. The genotypes of five PALB2 gene polymorphic sites (rs120963, rs16940342, rs249954, rs447529, and rs249935) were characterized by using the Sequenom MassARRAY platform.

Results: The data showed that the genotypes rs249954 CT (adjusted odds ratio [OR] = 1.52; 95% confidence interval [95% CI], 1.10-2.09), TT (adjusted OR = 2.36; 95% CI, 1.39-4.02), and CT/TT (adjusted OR = 1.65; 95% CI, 1.22-2.24) were associated with increased risk of breast cancer, respectively, relative to the CC genotype. Similarly, the rs120963 TC (adjusted OR = 1.89; 95% CI, 1.38-2.59), CC (adjusted OR = 3.88; 95% CI, 1.75-8.60), and TC/CC (adjusted OR = 2.05; 95% CI, 1.51-2.78) genotypes were associated with increased risk of breast cancer, respectively, relative to the TT genotype. Additionally, a weakly significant association was observed between G allele (AG/GG genotype) carriers of the rs249935 SNP in the sub-group of T1-2 (Adjusted OR = 1.43; 95% CI, 1.03-10.84) and negative lymphatic involvement (Adjusted OR = 3.23; 95% CI, 0.97-10.84) and risk of breast cancer.

Conclusions: This case-control study provided evidence that rs120963 and rs249954 of the PALB2 gene are associated with increased breast cancer risk, and that the association of rs249935 with breast cancer risk may be modified by the tumor pathological characteristics.