In terms of gene-gene interactions of circadian and melatonin pathway genes on the relationship with breast cancer, two-way interactions between ARNTL/MTNR1B, MTNR1B/NPAS2 and three-way interactions with MTNR1B/NPAS2/ARNTL was observed in a previous study18. The gene discussed is MTNR1B; the disease is breast cancer.