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

First things first – Let’s go Raptors!

Outline

Testicular cancer - Incidence The most common malignancy among young men 13% of cancers in individuals aged 15-29 in Canada Source: Canadian Cancer Society, 2015

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

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

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

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.

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

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

Methods Age-specific incidence Birth cohort models Data from: National Cancer Incidence Reporting System (1971-1992) Canadian Cancer Registry (1992-2015) Joinpoint regression for annual percent changes Incidence rate ratios (reference cohort 1946)

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

Results - Younger men (age 20-29) 1971-1981: APC 5.94 1981-2015: APC 1.92

Results - Young men (age 30-39) 1971-1994: APC 2.92 1994-2015: APC 1.17

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

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?

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

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

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

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

Next Steps - Mutational signatures G C G G T G

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

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.

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?

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

Results – Older age groups (age 60-69)