The role of polymorphisms in circadian pathway genes in breast tumorigenesis
The role of polymorphisms in circadian pathway genes in breast tumorigenesis
复制标题
昼夜节律通路基因多态性在乳腺肿瘤发生中的作用
DOI：
10.1007/s10549-010-1231-2
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发表时间：
2011-06-01
影响因子：
3.8
通讯作者：
Chen, Kexin
中科院分区：
文献类型：
--
作者：
Dai, Hongji;Zhang, Lina;Chen, Kexin
Disruption of the circadian rhythm or biological clock, which is regulated by a number of clock genes, including circadian locomotor output cycles kaput (CLOCK), period genes (PERs), and cryptochrome genes (CRYs), is a risk factor for breast cancer. We hypothesized that genetic variation in these clock genes may influence breast cancer risk. To test this hypothesis, we designed a hospital-based study that included 1,538 breast cancer patients and 1,605 healthy controls. We genotyped subjects for five single nucleotide polymorphisms (SNPs) and a length variant of the circadian clock genes and evaluated their associations with breast cancer risk. These polymorphisms were determined by TaqMan allelic discrimination assays and the polymerase chain reaction-restriction fragment length polymorphism method. Univariate logistic regression analysis showed that polymorphisms of theCLOCKandCRY1genes were associated with breast cancer risk. We found that carriers of theCLOCKCT and combined CT+TT genotypes had a significantly higher risk of breast cancer than carriers of the CC genotype (aOR = 1.35, 95% CI = 1.12-1.63 and aOR = 1.30, 95% CI = 1.09–1.56, respectively). Carriers of theCRY1GT genotype had a decreased risk of breast cancer (aOR = 0.84, 95% CI = 0.71–0.99). We also observed a lower risk of breast cancer in carriers of theCRY2 CC genotype who were ER-positive than in those who were ER-negative (OR = 0.15, 95% CI = 0.04–0.67). When stratified by theCLOCKgenotype, patients with theCLOCKCT/CRY2CC genotypes had significantly lower cancer risk than those with the GG genotype (aOR = 0.36, 95% CI = 0.14–0.95). Individuals carrying both theCLOCKCC andPER2AA genotypes had an increased cancer risk (aOR = 2.28, 95% CI = 1.22–4.26). Our study suggests that genetic variants of the circadian rhythm regulatory pathway genes contribute to the differential risk of developing breast cancer in Chinese populations.
