Circulating levels of biomarkers and risk of ductal carcinoma in situ of the breast in the UK Biobank study

Observational studies have shown associations between circulating levels of various biomarkers (eg, total cholesterol [TC], low-density lipoprotein cholesterol [LDL], insulin-like growth factor-1 [IGF-1], C-reactive protein [CRP] and glycated hemoglobin-1c [HbA1c]) and the risk of invasive breast cancer (IBC). Ductal carcinoma in situ of the breast (DCIS) is a nonobligate precursor of IBC and shares several risk factors with it. However, the relationship between these biomarkers and DCIS risk remains unexplored. We studied the association between circulating levels of TC, LDL-C, high-density lipoprotein cholesterol (HDL-C), Lipoprotein (a) (Lp-(a)), IGF-1, CRP and HbA1c, with the risk of DCIS in 156801women aged 40 to 69 years and breast cancer-free at enrolment when blood samples and information on demographic and health-related factors were collected. Incident cases of DCIS were ascertained during the follow-up via linkage to the UK cancer registries Multivariable-adjusted Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of interest. In all, 969 DCIS incident cases were diagnosed during 11.4 years of follow-up. Total cholesterol was inversely associated with the risk of DCIS (HR_{quintile(Q)5vsQ1} = 0.47, 95% CI: 0.27-0.82, P_trend = .008). Conversely, LDL-C was positively associated with DCIS risk (HR_Q3vsQ1 = 1.43, 95% CI: 1.01-2.04, HR_Q4vsQ1 = 1.60, 95% CI: 1.04-2.47, HR_Q5vsQ1 = 2.29, 95% CI: 1.36-3.88, P_trend = .004). In postmenopausal women, CRP had a weak positive association with DCIS risk, while HbA1c showed a nonlinear association with the risk. These results, in conjunction with those from previous studies on IBC, provide support for the association of several biomarkers with the risk of an early stage of breast cancer.