We and others recently established an association with breast cancer of the marker rs10235235, which maps to the CYP3A locus.15 This marker, which was initially identified through its association with urinary estrone glucuronide,16 a metabolite that is correlated with the sex hormone estradiol, is also associated with age at menarche. We found a statistical interaction between rs10235235 and age at menarche on breast cancer risk, which is therefore a gene-environment interaction under gene-environment dependence. However, rs10235235 is not known to be the causal variant, and we will show that the marker interaction does not imply an interaction at the causal variant.