In contrast, other Mendelian randomization studies have failed to show a causal association of HDL cholesterol and risk of colorectal, prostate, lung, and breast cancer [14, 16, 17, 46], and in one of the studies, genetically high levels of HDL cholesterol was contrarily associated with increased risk of estrogen receptor-positive breast cancer [16]. Here, ESR1 is linked to breast carcinoma.