The role of polymorphisms in circadian pathway genes in breast tumorigenesis

Abstract

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 the CLOCK and CRY1 genes were associated with breast cancer risk. We found that carriers of the CLOCK CT 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 the CRY1 GT 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 the CRY2 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 the CLOCK genotype, patients with the CLOCK CT/ CRY2 CC genotypes had significantly lower cancer risk than those with the GG genotype (aOR = 0.36, 95% CI = 0.14-0.95). Individuals carrying both the CLOCK CC and PER2 AA 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.

Association between PER3 length polymorphism and onco-hematological diseases and its influences on fatigue on awakening in patients

“…During the analysis of leukemia separately from the rest of the conditions, the genotypes 4/5 and 5/5 were observed to be associated with a statistically significant increased risk (OR = 1.99, CI95% 1.06-3.74, p = 0.030 adjusted for age, sex, educational level and city of residence). Individual studies showed no conclusive results for the above-mentioned polymorphism [19,20,41] . A meta-analysis carried out by Geng and colleagues [15] combining three retrospective studies (2,492 cancer patients and 2,749 controls) reported that individuals with 5 repetition alleles had 17% increased risk of cancer compared to individuals with the 4 repetition alleles.…”

“…Several studies hypothesized that PER3 VNTR polymorphism may alter the susceptibility to cancer [15] . Moreover, variants in the circadian genes (CRY2, PER1, NPAS2 and CSNK1E) have been associated with different types of cancer, including non-Hodgkin lymphoma, prostate and breast cancer [16][17][18][19][20] . Studies on the expression patterns of circadian genes (PER3 and CCG) show that there are significant differences between tumor tissue and the normal one adjacent to the tumor [21][22] .…”

Tea Consumption, Alcohol Drinking and Physical Activity Associations with Breast Cancer Risk among Chinese Females: a Systematic Review and Meta-analysis

“…After reviewing the full text of these studies in detail, a total of 39 articles, involving 100,452 participants from 14 provinces, municipalities and regions, were included in the final review (Appendix 1). Among these included studies, we identified 6 cohort studies (Li et al, 2005;Shannon et al, 2005;Wang et al, 2006;Dai et al, 2010;Pronk et al, 2011;Shrubsole et al, 2011;) and 33 case-control studies (Lu et al, 1992;Xu et al, 1997;Zhao et al, 1999;Tao et al, 2002;Zou et al, 2002;Zhang et al, 2003;Chow et al, 2005;Lee et al, 2005;Chou et al, 2006;Huang et al, 2006;Li et al, 2006;Jin, 2007;Ma, 2007;Zhang et al, 2007;Kallianpur et al, 2008;Ren, 2008;Wang et al, 2008;Shrubsole et al, 2009;Wang et al, 2009;Zhang et al, 2009;Qian et al, 2010;Shi et al, 2010;Bao et al, 2011;Dai et al, 2011;Leu et al, 2011;Zhang et al, 2011;Hou et al, 2012;Xu et al, 2012;Yu et al, 2012;Wang et al, 2013). According to the NOS items, 11 studies were evaluated as high quality, 25 studies as modest quality, and 3 studies as low quality, respectively.…”

Artificial light-at-night – a novel lifestyle risk factor for metabolic disorder and cancer morbidity

“…This result suggests the important role of the clock gene CRY in breast cancer development, whereas the overexpression of this gene inhibits the growth of breast cancer cells. In Chinese women, different mutations at the core clock genes contribute differently to the level of breast cancer risk [134].…”