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Médecine du travail du personnel hospitalier

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

Auteur     Shanbeh Zienolddiny
Auteur     Aage Haugen
Auteur     Jenny-Anne Sigstad Lie
Auteur     Helge Kjuus
Auteur     Kristine Haugen Anmarkrud
Auteur     Kristina Kjaerheim
Volume     15
Numéro     4
Pages     R53
Publication     Breast cancer research: BCR
ISSN     1465-542X
Date     Jul 3, 2013
Résumé     INTRODUCTION: Some studies suggest 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: A nested case-control study of Norwegian nurses comprising of 563 breast cancer cases and 619 controls was carried out within a cohort of 49402 Norwegian nurses, aged 35-74 years. We studied 60 SNPs in 17 genes involved in 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 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 noteworthy using both FPRP and BFDP tests. In regard to the effect of polymorphisms and night work several significant associations were observed. After applying FPRP and BFDP, in women with [greater than or equal to]4 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 3 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 [greater than or equal to]3 consecutive night shifts.

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