Breast Cancer Single-Nucleotide Polymorphisms: Statistical Significance and Clinical Utility

Extract

The completion of nine large genome-wide association studies ( 1–9 ) has focused attention on single-nucleotide polymorphisms (SNPs) as risk factors for breast cancer. Despite considerable progress, the scientific yield, practical application, and commercial exploitation of SNP profiling for disease risk remain topics of debate ( 10–13 ).

In this context, the study by Milne et al. ( 14 ) offers an excellent example of both the promise and challenges of current genetic epidemiological approaches to SNP genotyping for breast cancer risk. Drawing on an international consortium of 25 centers contributing DNA from more than 30 000 breast cancer case patients and 35 000 healthy control subjects, these investigators sought to confirm if an SNP that was not detected in their initial scan was associated with risk for breast cancer. They confirmed that this SNP on the long arm of chromosome 2 was associated with a 1.12-fold risk for invasive breast cancer in white women of European origin. Unlike the initial report ( 2 ), they found an association in both estrogen receptor–negative and estrogen receptor–positive breast cancer. Although highly statistically significant ( P  = 10 ⁻¹⁹ ), the clinical validity and biological implications of these findings, and those of many genome-wide association studies, require additional research.