Prediction of breast cancer risk based on profiling with common genetic variants

BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

A novel framework for predicting patients at risk of readmission

Uncertainty in decision-making for patients’ risk of re-admission arises due to non-uniform data and lack of knowledge in health system variables. The knowledge of the impact of risk factors will provide clinicians better decision-making and in reducing the number of patients admitted to the hospital. Traditional approaches are not capable to account for the uncertain nature of risk of hospital re-admissions. More problems arise due to large amount of uncertain information. Patients can be at high, medium or low risk of re-admission, and these strata have ill-defined boundaries. We believe that our model that adapts fuzzy regression method will start a novel approach to handle uncertain data, uncertain relationships between health system variables and the risk of re-admission. Because of nature of ill-defined boundaries of risk bands, this approach does allow the clinicians to target individuals at boundaries. Targeting individuals at boundaries and providing them proper care may provide some ability to move patients from high risk to low risk band. In developing this algorithm, we aimed to help potential users to assess the patients for various risk score thresholds and avoid readmission of high risk patients with proper interventions. A model for predicting patients at high risk of re-admission will enable interventions to be targeted before costs have been incurred and health status have deteriorated. A risk score cut off level would flag patients and result in net savings where intervention costs are much higher per patient. Preventing hospital re-admissions is important for patients, and our algorithm may also impact hospital income.