Testicular cancer and heredity

Testicular cancer is the most frequent form of cancer among young men, and much indicates that the foundation for the disease is laid already in fetal life. In this Norwegian-Swedish collaborative project, genes that may be important for the development of testicular cancer will be investigated.

Background

Testicular cancer is the most frequent form of cancer among young men, and in Norway around 270 men are affected annually by this type of cancer. It is still unknown why testicular cancer occurs, but there is consensus that both genetic and environmental factors play a role. There are strong indications that the foundations of the disease are laid already in fetal life. Brothers, sons and fathers of patients with testicular cancer are at increased risk for the disease. With the help of surgery, chemotherapy and radiation therapy, more than 95 percent of patients are cured.

The last 50 years have seen a sharp increase in the incidence of testicular cancer, and the incidence in Norway is one of the highest in the world. By comparison, Sweden has around half as much incidence of testicular cancer as Norway. The reason for this is unknown.

Purpose

The project is a collaboration between Norway (Cancer Registry of Norway and Oslo University College) and Sweden (Karolinska Institutet). We are particularly interested in investigating whether gene variants that regulate exposure to sex hormones in the womb affect the risk of this type of cancer. testisprosjekt220.jpg

In this connection, saliva samples will be collected from men who were diagnosed with testicular cancer in the period 1990-2006, and who were aged 18-45 years when they were diagnosed. The persons concerned will be contacted by letter and asked to participate in the project. Participation involves them providing a saliva sample. The parents will also receive a request to provide a saliva sample, but only after their son has given permission for them to be contacted.

The unique feature of this project is the collection of saliva samples – not only from former patients – but also from their parents. The samples will be used for genetic analyses. We imagine that genetic variations may have an impact on the risk of developing testicular cancer. Since testicular cancer most likely occurs already in fetal life, genetic variations in the mother may also be important.

The academic communities involved have extensive experience and expertise in testicular cancer research. The project is expected to provide valuable knowledge about the interaction between genes and the environment in foetal life with regard to the risk of developing testicular cancer. Furthermore, the study can contribute to a better understanding of the large difference in prevalence between Norway and Sweden. In the long term, the results can hopefully also help reduce the incidence of this type of cancer.

Publications

Levy M, Hall D, Sud A, Law P, Litchfield K, Dudakia D, Haugen TB, Karlsson R, Reid A, Huddart RA, Grotmol T, Wiklund F, Houlston RS, Turnbull C (2017). Mendelian randomisation analysis provides no evidence for a relationship between adult height and testicular cancer risk. Andrology, 5 (5), 914-922. PubMed 28804972

Wang Z, McGlynn KA, Rajpert-De Meyts E, Bishop DT, Chung CC, Dalgaard MD, Greene MH, Gupta R, Grotmol T, Haugen TB, Karlsson R, Litchfield K, Mitra N, Nielsen K, Pyle LC, Schwartz SM, Thorsson V, Vardhanabhuti S, Wiklund F, Turnbull C, Chanock SJ, Kanetsky PA, Nathanson KL, Testicular Cancer Consortium (2017)
Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor. Nat Genet, 49 (7), 1141-1147. PubMed 28604732

Litchfield K, Levy M, Orlando G, Loveday C, Law PJ, Migliorini G, Holroyd A, Broderick P, Karlsson R, Haugen TB, Kristiansen W, Nsengimana J, Fenwick K, Assiotis I, Kote-Jarai Z, Dunning AM, Muir K, Peto J, Eeles R, Easton DF, Dudakia D, Orr N, Pashayan N, UK Testicular Cancer Collaboration, PRACTICAL Consortium et al. (2017)
Identification of 19 new risk loci and potential regulatory mechanisms influencing susceptibility to testicular germ cell tumor. Nat Genet, 49 (7), 1133-1140. PubMed 28604728

Litchfield K, Holroyd A, Lloyd A, Broderick P, Nsengimana J, Eeles R, Easton DF, Dudakia D, Bishop DT, Reid A, Huddart RA, Grotmol T, Wiklund F, Shipley J, Houlston RS, Turnbull C (2015). Identification of four new susceptibility loci for testicular germ cell tumour. Nat Commun, 6, 8690. PubMed 26503584

Kristiansen W, Karlsson R, Rounge TB, Whitington T, Andreassen BK, Magnusson PK, Fosså SD, Adami HO, Turnbull C, Haugen TB, Grotmol T, Wiklund F (2015). Two new loci and gene sets related to sex determination and cancer progression are associated with susceptibility to testicular germ cell tumor
Hum Mol Genet, 24 (14), 4138-46. PubMed 25877299

Andreassen KE, Kristiansen W, Karlsson R, Aschim EL, Dahl O, Fosså SD, Adami HO, Wiklund F, Haugen TB, Grotmol T (2013). Genetic variation in AKT1, PTEN and the 8q24 locus, and the risk of testicular germ cell tumor. Hum Reprod, 28 (7), 1995-2002. PubMed 23639623

Karlsson R, Andreassen KE, Kristiansen W, Aschim EL, Bremnes RM, Dahl O, Fosså SD, Klepp O, Langberg CW, Solberg A, Tretli S, Magnusson PK, Adami HO, Haugen TB, Grotmol T, Wiklund F (2013). Investigation of six testicular germ cell tumor susceptibility genes suggests a parent-of-origin effect in SPRY4. Hum Mol Genet, 22 (16), 3373-80. PubMed 23640991

Kristiansen W, Andreassen KE, Karlsson R, Aschim EL, Bremnes RM, Dahl O, Fosså SD, Klepp O, Langberg CW, Solberg A, Tretli S, Adami HO, Wiklund F, Grotmol T, Haugen TB (2012). Gene variations in sex hormone pathways and the risk of testicular germ cell tumour: a case-parent triad study in a Norwegian-Swedish population. Hum Reprod, 27 (5), 1525-35. PubMed 22402210