Jaakko Kaprio – Laboratory of Genetic Epidemiology  –  PhD project 6

The Finnish Twin Study project has been operative at the University of Helsinki since the early ‘70s, under Prof. Jaakko Kaprio’s leadership. This project is comprised of data representing twin population cohorts, and sets out to investigate the genetic and environmental factors that regulate common and complex diseases, as well as their behavioural risk factors. Studies are done in close cooperation with many Finnish and foreign researchers. We offer one PhD project to undertake an inter-disciplinary project to assess how genetic and environmental factors contribute to the association of breast and skin cancer with other cancer types in families, using the NorTwinCan cohort data. 

Cumulative Incidence and Familial Risk of Developing Any Cancer Over Time in the NorTwinCan Cohort. The cumulative incidence is the risk of developing a first cancer over time within the full twin cohort; estimate is adjusted for censoring and competing risks of death. Familial risk is defined as the risk of developing any cancer given the twin’s co-twin also developed cancer. The extent to which the estimate of familial risk is higher than the cumulative incidence gives a sense of the magnitude of excess risk that may be associated with familial factors. Shaded areas indicate 95% confidence intervals; NorTwinCan, Nordic Twin Study of Cancer. 

Project 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 and Significance: A compelling finding from the Nordic Twin study on Cancer, NorTwinCan[1] revealed that when one twin develops cancer, the co-twin is also at an increased cancer risk, but usually at a different anatomical site. NorTwinCan has data from 357,377 twin individuals from Denmark, Finland, Norway and Sweden. Among the 1383 genetically identical, monozygotic (MZ) cancer-concordant pairs, 62% were discordant for the cancer site and among the dizygotic (DZ) cancer-concordant pairs, 74% (1437 pairs) were site discordant. Understanding the relationships between cancers at different sites can provide insights into genes increasing risk of ³2 cancers, but also discern shared hormonal or environmental putative inflammatory risk factors; this can be analyzed by comparing MZ and DZ twin pairs.

Objectives: (1) 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; (2) 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. (3) ESR6 will analyse 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.

Related readings

[1] Mucci, L.A. et al. Familial Risk and Heritability of Cancer Among Twins in Nordic Countries. JAMA 315, 68-76 (2016).