Principal Investigator: Dr Mark Powell
Institution: University of CambridgeTags: 37368, breast cancer, cancer, cardiovascular disease, featured, Gestational hypertension, Hypertension, PreEclampsia
Collaborator: Professor Christopher Benz – Buck Institute for Research on Aging, Novato, California, USA
Pregnancy has long been known to have a major impact on the developing breast and the future risk of breast cancer. Many studies have shown that hypertensive disorders of pregnancy (HDP) occur in as many as 10% of pregnancies, and are associated with lower future risk of breast cancer. HDP consists of gestational hypertension and preeclampsia, and both are characterized by the development of high blood pressure in pregnancy, usually after the 20th week of gestation. Our recent research has shown that the reduction for breast cancer can be as high as 90% in women with HDP that carry a specific common gene variant, and the initial objective of this study is to reconfirm these findings in the larger UK Biobank cohort. There is also evidence that HDP is associated with a lower risk of other cancers, and we will be examining whether this same gene variant impacts these risks as well.
Interestingly, HDP has also been shown to be associated with increased later life risk of hypertension, heart disease, and stroke, indicating that experiencing HDP can have both good and bad long-term health outcomes. Therefore, a second objective is to further explore this association and determine if this same gene variant predicts the future risk of developing cardiovascular disease in women who experience HDP.
The gene variant we will be studying is part of the insulin-like growth factor (IGF-1) system, which has a well-established role in both the development of cancer and cardiovascular disease. HDP are associated with inadequate blood flow to the placenta, which results in alterations of many hormones and growth factors, including lower levels of IGF-1. It appears that these lower levels interact with our observed genetic variant to protect the breast tissue in pregnancy, which is known to be a very vulnerable and critical time in breast development.
Achieving the aims of this study could improve the ability to predict the future risk of developing the two most significant age-associated health outcomes that women face, and thereby lead to more effective personalized screening and open the door to novel prevention strategies.
The size and data composition of the UK Biobank make it a perfect place to study the important relation of HDP and genetics to future health, and we expect the study to be completed in 12 months.
The development of hypertension during pregnancy has been associated with many critical later life consequences such as lower rates of breast cancer and increased risk of cardiovascular diseases. Our prior research has determined the lower risk of breast cancer is dependent on a common functional variant in the insulin-like growth factor receptor (IGF1R) gene. We hypothesize that this same variant also impacts the risk of cardiovascular disease and other types of cancer as well. Our major aims are:
1) Enhance and refine prior epidemiologic findings demonstrating significantly reduced breast cancer risk in women with a history of gestational hypertension and preeclampsia carrying a common functional IGF1R variant, rs2016347, by extending this observation to other types of cancer, and by evaluating the potential modifying role of other pregnancy factors such as age of first birth, parity, and birth weight.
2) Assess the impact of the rs2016347 genotype on the already well-documented increased future risk of cardiovascular disease in women with a history of gestational hypertension and preeclampsia by assessing outcomes such as hypertension, ischemic heart disease, cerebrovascular disease, and arterial stiffness index.
The initial scope was already expanded to include blood levels of IGF-1 which has been shown in prior studies to be associated with hypertensive disorders of pregnancy, and is relevant to our hypothesis that these levels along with carrying a functionally impaired IGF1R receptor result in the lower rates of breast and other cancers we are seeing in these women.
We would now like to look at specific IGF-1 and IGFBP3 SNPs which have been shown to be associated with IGF-1 levels to see if these play a role in determining cancer outcome in women with hypertensive disorders of pregnancy, as well as the possibility that these interact with our main SNP of interest as has been shown in prostate cancer in other studies.
Last updated Sep 16, 2019