(6) Genetic and environmental contribution to the association of breast and skin with other cancers in families – a twin study.

HYPOTHESIS

Genetic factors account for the excess cross-site sharing of cancer risk in sibling pairs

Background & Significance

The family of a patient with cancer may ask if their risk of cancer is elevated. There are fairly rare well-known cancer genes that run in some families. In such families, specific gene diagnosis and genetic counselling are needed. However, most cancers are not caused by such genes that increase cancer risk substantially. Nonetheless twin studies such as the Nordic Twin Study on Cancer (Mucci et al, JAMA 2016) show that most common cancers have a heritable component. Molecular genetic studies have started to identify the individual genes underlying this heritable component.

An important result from the large Nordic twin study was that in most twin pairs, also the genetically identical pairs (aka monozygotic twins), where at least one twin in the pair had cancer, the other twin did not. i.e. even for twins with the same genomic sequence, cancer does not always occur in both twins. Further, when both did have cancer, the  cancers were more often at different organs and sites in the body rather than at the same one.

Twin studies permit also assessment of the relative role of genetic versus environmental factors in the development of cancer. This project will look into the genetic and epigenetic factors underlying breast and skin cancers in twin pairs from the Finnish Twin Cohort.

Objectives

ESR6 will assess the risk of other cancers in the co-twin given BC in the first twin using appropriate survival models and adjustment for reproductive factors;

the profile of risk for cancer in the co-twin given skin cancer (either squamous or basal cell carcinoma, melanoma) in the twin. The analyses will be done separately for MZ and DZ pairs.

as well as distinct hormonal and inflammation-related pathways (with specific focus on ER, PR, AR and pro-inflammatory cytokines) indicated by genetic variants from GWAS. Specific risk factors such as alcohol use, physical inactivity, reproductive history (e.g. age-at-first-birth, number of children, hormone use) are available for twin pairs, where one twin has breast or skin cancer and the other twin has another associated cancer. A comparison group are pairs with an index cancer in one twin and no cancer in the other.

Enrolment in Doctoral degree(s):

  • University of Helsinki