The role of MTNR1B polymorphism on circadian rhythm-related cancer: a UK Biobank cohort study
Menée à partir de données de la "UK Biobank" portant sur 216 702 personnes (durée médiane de suivi : 8 ans), cette étude analyse l'effet du variant rs10830963 du gène du récepteur de la mélatonine 1B (MTNR1B) sur l'association entre le chronotype et le risque de cancer du sein (2 367 cas) ou de la prostate (2 866 cas)
A common G risk allele in the melatonin receptor 1B (MTNR1B, rs10830963) gene has been associated with altered melatonin signaling and secretion. Given that melatonin possesses anti-cancerogenic properties, we hypothesized that breast and prostate cancer risks vary by rs10830963 genotype. A total of 216,702 participants from the UK Biobank without cancer at baseline (aged 56.4 ± 8.0 years, 50.79% female) were included. Multivariable Cox regression adjusting for known risk factors for breast or prostate cancer was used to estimate the independent effects of the rs10830963 SNP and chronotype on cancer risk. Over a median follow-up of eight years, 2,367 (2.15% of women) incidences of breast cancer and 2,866 (2.69% of men) incidences of prostate cancer were documented in females and males, respectively. rs10830963 genotype is not associated with cancer risk independently (female Ptrend =0.103, male Ptrend =0.281). A late chronotype is associated with breast cancer risk in females (Ptrend =0.014), but not prostate cancer risk in males (Ptrend =0.915). Further stratification analysis revealed that the rs10830963 genotype is associated with a breast cancer risk in females with moderate evening chronotype (Ptrend =0.001), and late chronotype is associated with breast cancer risk in females who carry rs10830963 G risk allele (Ptrend =0.015). Our study suggests that having a late chronotype might increase the risk of breast cancer among females, while the effect of MTNR1B rs10830963 genotype on breast cancer risk is mediated by chronotype.