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

Breast Cancer Research

Kristina Kjærheim¹  Kristine Haugen Anmarkrud²  Helge Kjuus³  Jenny-Anne Sigstad Lie³  Aage Haugen²  Shanbeh Zienolddiny² 

[1] Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway;Department of Chemical and Biological Work Environment, National Institute of Occupational Health, PB 8149 Department, N-0033 Oslo, Norway;Department of Occupational Medicine and Epidemiology, National Institute of Occupational Health, Oslo, Norway

关键词: SNP;    Night shift;    Clock;    Circadian;    Breast cancer;   

Others  :  794381
DOI  :  10.1186/bcr3445

 received in 2012-10-24, accepted in 2013-07-03,  发布年份 2013

【 摘 要 】

Introduction

Some 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.

Methods

We 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).

Results

In 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).

Conclusions

Significant 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.

【 授权许可】

   
2013 Zienolddiny et al.; licensee BioMed Central Ltd.

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