The role of MTNR1B polymorphism on circadian rhythm‐related cancer: A UK Biobank cohort study

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 anticancerogenic 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 8 years, 2367 (2.15% of women) incidences of breast cancer and 2866 (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 = .103, male Ptrend = .281). A late chronotype is associated with breast cancer risk in females (Ptrend = .014), but not prostate cancer risk in males (Ptrend = .915). Further stratification analysis revealed that the rs10830963 genotype is associated with a breast cancer risk in females with moderate evening chronotype (Ptrend = .001) and late chronotype is associated with breast cancer risk in females who carry rs10830963 G risk allele (Ptrend = .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. What's new? Circadian misalignment is closely related to the onset of hormone‐dependent cancers, while melatonin exerts anticancerogenic properties. This is the first study to examine the potential interaction between a common G risk allele in the melatonin receptor 1B (MTNR1B, rs10830963) gene and an individual's chronotype on cancer risk. The findings suggest an effect of late chronotype on breast cancer risk that is stronger in rs10830963 G allele carriers. The rs10830963 G allele may only increase breast cancer risk among females with a late chronotype. These findings could help inform breast cancer risk estimation and direct new lifestyle interventions.