Comparison of the effects of genetic and environmental risk factors on in situ and invasive ductal breast cancer

Little is known about the etiology of in situ ductal breast cancer (DCIS) or what influences its possible progression to invasive ductal disease. Comparison of risk factors for DCIS and invasive ductal cancer may throw some light on these issues. We estimated relative risks for DCIS and invasive ductal breast cancer according to 12 genetic and eight environmental risk factors among 1.1 million postmenopausal women in a large prospective UK study. There was no strong evidence of a different association with DCIS versus invasive ductal cancer for any of the 12 susceptibility loci examined. We also found similar associations of age at menarche, age at first birth, parity, age at menopause, family history of breast cancer and use of hormone replacement therapy with DCIS and invasive ductal cancer. Only body mass index (BMI) showed a clear difference in association in that it was positively associated with the risk of invasive ductal cancer but not DCIS (RRs per 5 kg/m2 = 1.20 and 1.01, respectively; p-value for heterogeneity = 0.002). The very similar risk factor profiles observed here for DCIS and invasive ductal cancer suggest that DCIS is a precursor of invasive ductal cancer and most risk factors affect the risk of invasive ductal cancer primarily through their effects on the risk of DCIS. The lack of association between BMI and DCIS suggests a greater influence of BMI on disease progression.