Women who experience HDPs have 41% lower risk for developing nonbreast cancer and have lower later-life blood pressures if they inherit a T allele of the common functional IGF1R variant rs2016347. These novel findings add to a growing body of epidemiologic evidence pointing to a clinically significant exposure interaction between HDPs and rs2016347 (effect modification) and strongly implicate a mechanistic role for the IGF1 axis in driving both cardiovascular and cancer risk, particularly in women with a history of HDPs. Because nonbreast cancers afflict 30% of women in their lifetime, confirmation of this study's findings could lead to improved individualized cancer screening, as well as novel prevention strategies.
Working with Mark Powell, MD MPH at the Buck Institute, I help examine genotype and blood biomarkers and their associations with invasive breast cancer.
Terminal duct lobular units (TDLUs) are the anatomic sites of breast cancer initiation, and breast tissue involution resulting in lower TDLU counts has been associated with decreased breast cancer risk. The insulin-like growth factor (IGF) pathway plays a role in breast involution, and systemic changes in this developmental pathway occur with hypertensive disorders of pregnancy (HDP), which have also been associated with lower breast cancer risk, especially in women carrying a functional variant of IGF1R SNP rs2016347. We proposed that this breast cancer protective effect might be explained by increased breast tissue involution.