Association of common PALB2 polymorphisms with breast cancer risk: a case-control study.
OBJECTIVE
The PALB2 gene has an essential role in BRCA2-mediated DNA double-strand break repair and intra-S phase DNA damage checkpoint control, and its mutations are moderately associated with breast cancer susceptibility. This study was designed to investigate the common variants of PALB2 and their association with breast cancer risk.


METHODS
Four single nucleotide polymorphisms (SNP; rs249954, rs249935, rs120963, and rs16940342) which tagged all 19 of the reported SNPs (minor allele frequency >0.05) covering PALB2 were selected and genotyped in 1,049 patients with breast cancer and 1,073 cancer-free controls in a female Chinese population.


RESULTS
Based on the multiple hypothesis testing with the Benjamini-Hochberg method, tagging SNPs (tSNP) rs249954, rs120963, and rs16940342 were found to be associated with an increase of breast cancer risk (false discovery rate-adjusted P values of 0.004, 0.028, and 0.049, respectively) under the dominant model. tSNP rs249954 was associated with a 36% increase of breast cancer risk [adjusted odds ratio (OR), 1.36; 95% confidence intervals (CI), 1.13-1.64; P = 0.001; TT/TC versus CC genotypes]. The adjusted OR for rs120963 was 1.25 (95% CI, 1.04-1.49; P = 0.014; CC/CT versus TT genotypes). For rs16940342, the adjusted OR was 1.21 (95% CI, 1.02-1.45; P = 0.037; GG/GA versus AA genotypes). Based on an additive model, tSNPs rs249954 and rs120963 were associated with an increase of breast cancer risk (P = 0.005 and 0.019; respectively), with the false discovery rate-adjusted P values being 0.020 and 0.038, respectively.


CONCLUSIONS
Our data suggest that the variants of PALB2 confer low-penetrance breast cancer susceptibility in a Chinese population.
Chen
Peizhan
P
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; Graduate School of the Chinese Academy of Sciences, Nanjing, China.
Liang
Jie
J
Wang
Zhanwei
Z
Zhou
Xiaoyi
X
Chen
Lu
L
Li
Mian
M
Xie
Dong
D
Hu
Zhibin
Z
Shen
Hongbing
H
Wang
Hui
H
D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins