Using SNP genotypes to improve the discrimination of a simple breast cancer risk prediction model

Dite GS, Mahmoodi M, Bickerstaffe A, Hammet F, Macinnis RJ, Tsimiklis H, Dowty JG, Apicella C, Phillips KA, Giles GG, Southey MC, Hopper JL (2013) Using SNP genotypes to improve the discrimination of a simple breast cancer risk prediction model. Breast Cancer Res Treat 139:887-896

It has been shown that, for women aged 50 years or older, the discriminatory accuracy of the Breast Cancer Risk Prediction Tool (BCRAT) can be modestly improved by the inclusion of information on common single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risk. We aimed to determine whether a similar improvement is seen for earlier onset disease. We used the Australian Breast Cancer Family Registry to study a population-based sample of 962 cases aged 35-59 years, and 463 controls frequency matched for age and for whom genotyping data was available. Overall, the inclusion of data on seven SNPs improved the area under the receiver operating characteristic curve (AUC) from 0.58 (95 % confidence interval [CI] 0.55-0.61) for BCRAT alone to 0.61 (95 % CI 0.58-0.64) for BCRAT and SNP data combined (p < 0.001).="" for="" women="" aged="" 35-39="" years="" at="" interview,="" the="" corresponding="" improvement="" in="" auc="" was="" from="" 0.61="" (95="" %="" ci="" 0.56-0.66)="" to="" 0.65="" (95="" %="" ci="" 0.60-0.70;="" p="0.03)," while="" for="" women="" aged="" 40-49="" years="" at="" diagnosis,="" the="" auc="" improved="" from="" 0.61="" (95="" %="" ci="" 0.55-0.66)="" to="" 0.63="" (95="" %="" ci="" 0.57-0.69;="" p="0.04)." using="" previously="" used="" classifications="" of="" low,="" intermediate="" and="" high="" risk,="" 2.1="" %="" of="" cases="" and="" none="" of="" the="" controls="" aged="" 35-39="" years,="" and="" 10.9="" %="" of="" cases="" and="" 4.0="" %="" of="" controls="" aged="" 40-49="" years="" were="" classified="" into="" a="" higher="" risk="" group.="" including="" information="" on="" seven="" snps="" associated="" with="" breast="" cancer="" risk,="" improves="" the="" discriminatory="" accuracy="" of="" bcrat="" for="" women="" aged="" 35-39="" years="" and="" 40-49="" years.="" given,="" the="" low="" absolute="" risk="" for="" women="" in="" these="" age="" groups,="" only="" a="" small="" proportion="" are="" reclassified="" into="" a="" higher="" category="" for="" predicted="" 5-year="" risk="" of="" breast="">