1. 1. The rising incidence of testicular cancer among young men in Canada
Dr. Darren Brenner, PhD

2. First things first – Let’s go Raptors!

3. Outline

4. Testicular cancer - Incidence
The most common malignancy among young men
13% of cancers in individuals aged in Canada
Source: Canadian Cancer Society, 2015

5. Testicular cancer - Histology
Non-Germ Cell ~5-10%
(Stromal Leydig Sertoli)
Germ Cell ~>90-95%
Seminomas
Non- Seminomas
Embryonal
carcinoma
Yolk sac
carcinoma
Chorio-
carcinoma
Teratoma

6. Testicular cancer - Outcomes
Survival is stage dependent and worse for non-seminomas
Localized – 99% 5-year survival
Regional – 96% 5-year survival
Distant – 73% 5-year survival

7. Testicular cancer - Background
Known risk factors:
Personal or family history of testicular cancer
Cryptorchidism
Height
Many hypothesized risk factors with weak evidence

8. Incidence is increasing in high-income countries
1.5-2% per year since 1973
1-5% per year since 1973
No major changes in diagnostic or screening practices.

9. Incidence is increasing in high-income countries
1.5-2% per year since 1973 ??
1-5% per year since 1973

10. Objectives of Analyses:
To investigate the incidence trends of testicular cancer between 1971 and 2015
Explore age-period-cohort effects in incidence trends
Pilot work to examine factors driving trends

11. Methods
Age-specific incidence
Birth cohort models
Data from:
National Cancer Incidence Reporting System ( )
Canadian Cancer Registry ( )
Joinpoint regression for annual percent changes
Incidence rate ratios (reference cohort 1946)

12. Results - Overall 7.06 per 100,000 3.77 per 100,000
Overall Incidence in Canada has been increasing since 1971
3.77 per 100,000
7.06 per 100,000
2015
1971
Age-standardized rates

13. Results - Younger men (age 20-29)
: APC 5.94
: APC 1.92

14. Results - Young men (age 30-39)
: APC 2.92
: APC 1.17

15. Results - Cohort effects
More recent cohorts at higher risk compared to reference (1946)
Uninterrupted increase after 1945
IRR
Year

16. Interpretation Incidence of testicular cancer is increasing in Canada
More recent cohorts are at greater risk
– implications for risk factors
Research needed on in utero, environmental, and lifestyle exposures – NEW EXPOSURES?

17. Next Steps Follow-up analysis by histological type
Etiologic study to examine novel risk factors
Tumor mutational signatures

18. Next Steps - Upcoming research
Pilot study
Questionnaire development
Literature review
What are the known and hypothesized risk factors?
Occupational, environmental, early-life, lifestyle exposures
Innovative approach/
Study design

19. Next Steps - Pilot study
Cases and controls
Baseline health information
Residential history
Occupational history
Environmental exposures
Mothers of cases and controls
Parental occupational history
Lifestyle habits
Events during gestation
Medical history
Environmental exposures
Bio-samples
Blood and urine samples
Exposure levels of relevant contaminants
Correlated with questionnaire data

20. Next Steps - Mutational signatures
We can use the genome to identify “causes” of cancer

21. Next Steps - Mutational signatures
G C G
G T G

22. Next Steps - Mutational signatures Preliminary results
Preliminary analyses from TCGA data
Mealey, 2019 in prep

23. Preliminary results
Signature 8 was seen in a quarter of young-onset testicular tumours, but none of the older-onset tumours. The etiology of Signature 8 is unknown.

24. Next Steps – Collaborative team
All together: a broader understanding of testicular cancer in Canada
Who is affected?
What contributes to risk?
How can we prevent it?

25. Acknowledgements - Team
Nicole Mealey, BSc
Yibing Ruan, PhD MPH
Emily Heer, MSc
Cheryl Peters, PhD
Daniel Heng, MD
Shelley Harris, PhD

26. Results – Older age groups (age 60-69)