近日,中科院上海生科院营养科学研究所的王慧研究组在中国汉族女性乳腺癌和PALB2基因多态性之间的关联研究取得新进展,其研究论文发表于《临床癌症研究》(Clinical Cancer Research (2008. Sep 15; 14 : 5931-37))。
PALB2是重要抑癌基因BRCA2向细胞核内的转移定位及核内稳定的协同因子,在保持基因组稳定和调节细胞周期过程中起重要作用。该基因发生突变能够引起2倍于正常人群的乳腺癌发病率。该项研究与南京医科大学沈洪兵教授研究组合作,采用病例-对照(Case-Control)的研究方法,在1049例病人和1073例对照中首次发现PALB2基因上3个SNP位点rs249954、rs120963和rs16940342和中国汉族女性乳腺癌的易感性相关。这为我国乳腺癌高危人群的筛选和预警提供了重要的理论依据。(生物谷Bioon.com)
生物谷推荐原始出处:
Clinical Cancer Research,2008. Sep 15; 14 : 5931-37,doi: 10.1158/1078-0432.CCR-08-0429
Association of Common PALB2 Polymorphisms with Breast Cancer Risk: A Case-Control Study
Peizhan Chen1, Jie Liang2, Zhanwei Wang2, Xiaoyi Zhou2, Lu Chen1, Mian Li1, Dong Xie1, Zhibin Hu2, Hongbing Shen2 and Hui Wang1
Authors' Affiliations: 1 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 and 2 Laboratory of Reproductive Medicine, Cancer Center, Nanjing Medical University, Nanjing, China
Purpose: 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.
Experimental Design: 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.