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Why is breast cancer sometimes a lethal disease?

Research project Why is breast cancer sometimes a lethal disease and sometimes indolent without symptoms during decades? The overriding goal of this project is to investigate whether there is a heritable background for the fact that breast cancer sometimes develops into a lethal disease.

If one of my parents died from a cancer, which are my odds if I get the same cancer? Our studies based on the huge Swedish Multigeneration Registry have given clear evidence for heritability of the prognosis in cancer. If a mother died from breast cancer there is an increased risk for her daughter who also contracts breast cancer to succumb to the disease. Corresponding observation was done for father/son with prostate cancer. Also in renal cell cancer and bladder cancer we obtained corresponding findings. Studies of other cancer forms did not give clearcut evidence. Register studies as well as investigations on biologic material from specimen banks have given clear evidence for genetic variants governing the probability of a cancer to develop into a life threatening disease. We have now started a project aiming at disclosure of the genetic background in a genome-wide association study, meaning that the major part of the variation of the human genome can be captured on the same occasion.

Project overview

Project period:

2008-10-23 – 2015-12-31

Funding

Finansår , 2006, 2007, 2008

huvudman: Per Lenner, finansiar: Cancerfonden, y2006: 400, y2007: 400, y2008: 400,

Participating departments and units at Umeå University

Department of Radiation Sciences

Project description

If one of my parents died from a cancer, which are my odds if I get the same cancer? Our studies based on the huge Swedish Multigeneration Registry have given clear evidence for heritability of the prognosis in cancer. If a mother died from breast cancer there is an increased risk for her daughter who also contracts breast cancer to succumb to the disease. [1]. Corresponding observation was done for father/son with prostate cancer. [2]. Also in renal cell cancer and bladder cancer we obtained corresponding findings. Studies of other cancer forms did not give clearcut evidence.

There is an obvious genetic background for the findings from the register studies. Evidence came from our study of gene variants in blood cells of the angiogenesis factor VEGF. Some variants were strongly correlated with important prognostic factors in breast cancer. [3]. We also showed that variants of the gene for PAI-1, which is an important factor for the invasive capacity of tumours, has prognostic bearing in breast cancer and colorectal cancer. [4, 5]. Integrins have similar functions and also for them we found genetic variants governing prognosis in breast cancer. There are a number of genes with implications for chromosomal instability (CIN genes), another important factor in cancer progression. Also in this case we observed a strong correlation between gene variants and prognosis in breast cancer. A number of other genetic variants were studied without evidence of association with breast cancer prognosis. All these studies were done on blood cells from biobanks and therefore concerned constitutional genetic variation and not the gene alterations that are always found in studies of tumour tissue.

Telomers are of great importance for the stability and integrity of chromosomes at mitosis. In collaboration with Dr.Göran Roos´ research group we observed that long telomers in blood cells were associated with shortened survival in breast cancer

Register studies as well as investigations on biologic material from specimen banks have given clear evidence for genetic variants governing the probability of a cancer to develop into a life threatening disease. We have now started a project aiming at disclosure of the genetic background in a genome-wide association study, meaning that the major part of the variation of the human genome can be captured on the same occasion. Associations between genetic variants dispersed over the entire genome and survival in breast cancer will be analysed in appropriate statistical models.

Disclosure (and confirmation in independent studies) of genetic variants that have implications on tumour development and prognosis in cancer may be of great importance for the oncology of the future. It has potential to increase our knowledge of basic biological mechanisms governing cancer progression. Such knowledge can in turn give rise to development of methods for cancer prevention and cancer therapy.