M2: Cancer treatment and genetic instability in relation to the health of the offspring

This study is performed at Malmø University Hospital at the Department of Growth and Reproduction in collaboration with Danish health registers.

Testicular germ cell cancer (TGCC) is the most common neoplasm in men aged 25-40 years. The incidence of TGCC has increased by a factor 3-4 the past 50 years. It has previously been published – based on Swedish and Danish registry data including almost 1 800 000 births – that children of male cancer survivors, conceived after the cancer diagnosis was made, had 20% higher risk for major congenital abnormalities than the offspring of fathers with no history of cancer. The study only showed the relation but nothing about the mechanism(s) behind the findings. One hypothesis could be both the paternal cancer and child defect are due to a constitutional genetic instability in the male. Another explanation might be that the genetic alternations passed on to the offspring are induced by cancer treatment administered to the father.

This project falls into two distinct parts:

An epidemiological part with the following hypothesis:
1. Children conceived by male cancer survivors (MCS) have at higher risk of morbidity than the offspring of men not diagnosed with cancer?
2. The risk of congenital malformations among the offspring of MCS is also increased among the children conceived prior to cancer diagnosis, i.e. indicating no effect of cancer therapy?

A molecular part with the following questions:
3. Is the prevalence of genetic aberrations increased in leukocytes of men treated for childhood or testicular cancer?
4. Is the ratio of genetic abnormalities higher, as compared to leukocytes, in the spermatozoa of testicular and childhood cancer survivors?
5. Is the frequency of genetic anomalies seen in leukocytes or in spermatozoa related to cancer type or treatment protocol?

The epidemiological part of the study will be based on register registry data for 1.8 million children born in Denmark and in Sweden during the period 1994-2005. For the molecular studies, biological material already collected and stored in the biobank in Malmø (leukocyte and sperm DNA) from more than 300 testicular cancer and 150 childhood cancer survivors as well as from healthy controls will be used.

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