Analysis of polymorphisms in the circadian-related genes and breast cancer risk in Norwegian nurses working night shifts

Abstract

IntroductionSome studies have suggested that night work may be associated with an increased risk of breast cancer in nurses. We aimed to explore the role of circadian gene polymorphisms in the susceptibility to night work-related breast cancer risk.MethodsWe conducted a nested case-control study of Norwegian nurses comprising 563 breast cancer cases and 619 controls within a cohort of 49,402 Norwegian nurses ages 35 to 74 years. We studied 60 single-nucleotide polymorphisms (SNPs) in 17 genes involved in the regulation of the circadian rhythm in cases and controls. The data were analyzed in relation to the two exposure variables "maximum number of consecutive night shifts ever worked" and "maximum number of consecutive night shifts worked for at least 5 years." The odds of breast cancer associated with each SNP was calculated in the main effects analysis and in relation to night shift work. The statistically significant odds ratios were tested for noteworthiness using two Bayesian tests: false positive report probability (FPRP) and Bayesian false discovery probability (BFDP).ResultsIn the main effects analysis, CC carriers of rs4238989 and GG carriers of rs3760138 in the AANAT gene had increased risk of breast cancer, whereas TT carriers of BMAL1 rs2278749 and TT carriers of CLOCK rs3749474 had reduced risk. The associations were found to be noteworthy using both the FPRP and BFDP tests. With regard to the effect of polymorphisms and night work, several significant associations were observed. After applying FPRP and BFDP in women with at least four night shifts, an increased risk of breast cancer was associated with variant alleles of SNPs in the genes AANAT (rs3760138, rs4238989), BMAL1 (rs2290035, rs2278749, rs969485) and ROR-b (rs3750420). In women with three consecutive night shifts, a reduced risk of breast cancer was associated with carriage of variant alleles of SNPs in CLOCK (rs3749474), BMAL1 (rs2278749), BMAL2 (rs2306074), CSNK1E (rs5757037), NPAS2 (rs17024926), ROR-b (rs3903529, rs3750420), MTNR1A (rs131113549) and PER3 (rs1012477).ConclusionsSignificant and noteworthy associations between several polymorphisms in circadian genes, night work and breast cancer risk were found among nurses who had worked at least three consecutive night shifts.

Breast cancer risk, nightwork, and circadian clock gene polymorphisms

“…Additionally, it has been hypothesized that the increased risk of breast cancer among women working at night could be modulated by genetic polymorphisms in the circadian pathway genes. A few studies highlighted interactions between nightwork and specific circadian gene variants in relation to breast cancer (Monsees et al 2012, Grundy et al 2013, Zienolddiny et al 2013, but again none of the reported interactions were replicated.…”

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

“…A positive correlation between expression level of core clock genes and breast cancer risk has been reported for the gene TIMLESS in peripheral blood lymphocytes of 80 breast cancer women compared with age-matched tumor-free equal cases [131]. Researchers have also discovered a significant association between number of successive night shifts and risk of breast cancer in women who have worked night shifts with single nucleotide polymorphism in the gene BMAL1 and related orphan receptor β (ROR-β), r [128]. The association between high risk of breast cancer and single nucleotide polymorphism in other core clock genes, such as BMAL2 and PER3 has been reported [128].…”

“…Researchers have also discovered a significant association between number of successive night shifts and risk of breast cancer in women who have worked night shifts with single nucleotide polymorphism in the gene BMAL1 and related orphan receptor β (ROR-β), r [128]. The association between high risk of breast cancer and single nucleotide polymorphism in other core clock genes, such as BMAL2 and PER3 has been reported [128].…”

“…Per2 has been demonstrated to be a tumor suppressor gene in MCF-7 breast cancer epithelial cells [126] by linking the Estrogenreceptor-α (ER-α) to the circadian system regulating its degradation [127]. Single nucleotide polymorphism in the core clock genes BMAL1 and CLOCK has been suggested to be associated with high risk of breast cancer among night work-shift Norwegian nurses [128].…”

Kreftpasient i 50-årene med plagsom hjertebank

“…faktorer, men også biologiske prosesser i menneskekroppen: normal metabolisme (sto ski e), mikroora, in ammasjon, oksidativt stress og infeksjoner (Haugen 2015). Dette krever gode registre med demogra ske data og videre arbeid med identi kasjon av gode biomarkører for eksponering.…”