Interestingly, certain gene variations were associated with decreased BC risk (e.g. RAD52, OCT4, FASL, IGFIR, APE1, BARD1, IL4, IL21) (Kang et al., 2013; Liu et al., 2013a; You et al., 2013; Joshi et al., 2014b; Kang et al., 2014; Tulsyan et al., 2014; Xu et al., 2014; Wu et al., 2015), or both increased and decreased risk, depending on the gene variation investigated (e.g. MTHFR, ESR1, VEGF, FAS, OGG1, TGFB1) (Pooja et al., 2013; Kapahi et al., 2014; Lu et al., 2014; Luo et al., 2014; Wang et al., 2014c; Xu et al., 2014; Yu et al., 2014; Lu et al., 2015; Son et al., 2015). The gene discussed is ESR1; the disease is breast cancer.