testicular cancer in new zealand: a mystery to be solved · •testicular cancer is, well, cancer...
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![Page 1: Testicular cancer in New Zealand: A mystery to be solved · •Testicular cancer is, well, cancer of the testis. –Almost all (95%)1 TC [s begin within germ cells –the cells that](https://reader033.vdocuments.us/reader033/viewer/2022053101/6060af12a4940151121029ed/html5/thumbnails/1.jpg)
Dr Jason Gurney
Department of Public Health,
Wellington School of Medicine and Health Sciences,
University of Otago
Testicular cancer in New Zealand:
A mystery to be solved
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Our questions for today:• Why is testicular cancer important?
• What causes testicular cancer?
• Why might New Zealand have an important role to play in understanding this disease?
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“The most challenging part of epidemiology…is to understand
the reasons for human variability, including the reasons some
people get a disease and others do not.”1
1 Willcox (2010). Fertility and pregnancy: an epidemiologic perspective. Oxford Press.
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What is TC?• Testicular cancer is, well, cancer of the
testis.
– Almost all (95%)1 TC’s begin within germ cells – the cells that give rise to sperm.
1 Huyghe, et al. (2003). The Journal of Urology, 170, p5-11.
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Source: Dieckmann, et al. (2013). Nature Reviews Urology, 10, p703-712.
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Tumour cellNormal germ cells
Source: Male Genital Pathology Index, University of Utah (http://library.med.utah.edu/WebPath)
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Why is testicular cancer important?
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In a relative sense, testicular cancer (TC) is rare.
![Page 10: Testicular cancer in New Zealand: A mystery to be solved · •Testicular cancer is, well, cancer of the testis. –Almost all (95%)1 TC [s begin within germ cells –the cells that](https://reader033.vdocuments.us/reader033/viewer/2022053101/6060af12a4940151121029ed/html5/thumbnails/10.jpg)
99
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Selected Sites
Cancer Among NZ Males, 2010
Source: MoH New Zealand Cancer Registry Historical Summary, 1948-2011
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However, testicular cancer is the most common cancer to afflict young men…
by a considerable margin.
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-1
1
3
5
7
9
11
13
15
20-24 25-29 30-34 35-39
Cru
de
Age
-Sp
ecif
ic R
ate
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Age Group (years)
Cancer Among U.S. Males, 2010
TestisMelanomaColorectalNon-Hodgkin LymphomaKidneyBrain
Hodgkin LymphomaLungStomachPancreasProstate
Leukemia
Source: SEER Cancer Statistics Review, 1975-2011. National Cancer Institute.
![Page 13: Testicular cancer in New Zealand: A mystery to be solved · •Testicular cancer is, well, cancer of the testis. –Almost all (95%)1 TC [s begin within germ cells –the cells that](https://reader033.vdocuments.us/reader033/viewer/2022053101/6060af12a4940151121029ed/html5/thumbnails/13.jpg)
New Zealand has some of the highest rates of TC in the world.
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Age-standardised incidence of TC (1998-2002)
1Chia, et al. (2010). Cancer Epidemiol Biomarkers Prev, 19, p1151-1159.
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Rates of TC are increasing steadily worldwide,1
particularly among some populations.
No-one knows why.
1 Huyghe, et al. (2003). The Journal of Urology, 170, p5-11.
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True to form, rates of TC in New Zealand are also increasing steadily over time:
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0.0
2.0
4.0
6.0
8.0
10.0
1950 1960 1970 1980 1990 2000 2010
Age
-Sta
nd
ard
ised
Rat
e (p
er 1
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Year of Diagnosis
Rates of TC in NZ, 1950-2010
Source: MoH New Zealand Cancer Registry Historical Summary, 1948-2011
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Why about the patients?
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The Dirty ‘P’ Word…Prognosis• Mercifully, survival among patients with
TC is high.
– We expect 90-100% will survive, for two main reasons:
1. A tendency for this cancer to be detected early;
2. The sophistication of modern treatment techniques.
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The Dirty ‘P’ Word…Prognosis• However, mortality isn’t the only
important outcome.
– Around a third of TC survivors will be left infertile after treatment.
– Increased risk of other sexual dysfunctions (like erectile dysfunction).
– Because TC occurs mostly among young men, it casts a long shadow.
1 Brydøy, et al. (2005). J Nat Cancer Institute, 2005;97(21):1580-88.
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The Dirty ‘P’ Word…Prognosis• Also, high overall survival could mask
survival inequalities.
– For example, Māori men are more than twice as likely to die of TC1 than European/Other men:
1 Gurney, et al. (2015). Cancer Causes and Control, 26, p561-569.
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0.780.8
0.820.840.860.88
0.90.920.940.960.98
1
0 1 2 3 4 5 6 7 8 9 10
Cru
de
Can
cer-
Spec
ific
Su
rviv
al
Years of Follow-Up
Kaplan-Meier Survival Curve
~
Maori
Euro/Other
1 Gurney, et al. (2015). Cancer Causes and Control, 26, p561-569. *Cancer-specific HR adjusted for age, stage, deprivation and rurality.
Adjusted HR:*
2.29(1.14-4.59)
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What causes TC?
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Unfortunately, the aetiology of TC remains obscure.
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Only a few ‘strong’ risk factors have been established:
• Age;
• Previous TC;
• Family history;
• ‘Cryptorchidism’.
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Aside from age, these known risk factors only account for a small
number of TC cases.
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Because of this aetiologicalobscurity, TC is a heavily-
researched area…
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…and as a result, there have been a myriad of other exposures
associated (rightly or wrongly) with TC development:
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Curiouser and Curiouser
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Worldwide, the incidence of TC is (by far) the greatest among those
ethnic groups who trace their ancestry to Northern Europe.1
1 McGlynn & Cook (2010). Chapter 2, Male Reproductive Cancers. Springer.
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In the U.S., White men are four-to-five times more likely to
develop TC than Black men...1
1 McGlynn, et al. (2003). Cancer; 97, p63–70.
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…and three-to four times more likely than Asian or Pacific Men.1
1 Chien, et al. (2014). Cancer; 120, p2728-2734.
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But in New Zealand, we’ve observed something very
peculiar:
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Source: Sarfati, et al. (2010). International Journal of Cancer, 128, p1683-1691.
Incidence of TC in NZ by Ethnicity, 1981-2004
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In an updated study covering the years 2000-2011, Māori men
were 80% more likely to develop TC than Euro/Other men.1
(Age-adjusted RR=1.80, 95% CI 1.58-2.05)
1 Gurney, et al. (2015). Cancer Causes and Control, 26, p561-569.
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Māori men were also three-times more likely than Pacific men to
develop TC over this time period.(Age-adjusted RR=3.13, 95% CI 2.28-4.29)
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This is really weird.
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Curiouser…
The New Zealand context is the only (known) example where a non-White population experiences the greatest
rates of TC.1
1 McGlynn & Cook (2010). Chapter 2, Male Reproductive Cancers. Springer.
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…and Curiouser:
The low rates of TC found among Pacific New Zealanders is a rare example
where disease incidence does not move in parallel between Māori and Pacific.
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“Given the lack of understanding of the aetiology of testicular cancer, the unusual patterns identified in the New Zealand
context may provide some etiological clues for future novel
research.”1
1 Sarfati, et al. (2010). International Journal of Cancer, 128, p1683-1691.
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In other words, we have a unique opportunity in New Zealand to both explain an inequity and
strengthen aetiological evidence.
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So that’s what we’re doing.
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Testicular Cancer in New Zealand (TCNZ) Study
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The TCNZ Study• Case-control study design - ~400 TC cases,
400 non-TC controls (150 Māori in each).
• Collecting environmental exposure data via interview, and genetic exposure data via saliva sample.
• Also interviewing mothers of cases/controls, to look at exposures during pregnancy and early-life.
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Our burning questions:
– Why do Māori men suffer the highest rates of testicular cancer in New Zealand? What is driving this disparity?
– What might we learn about the factors that cause testicular cancer in general by explaining this disparity?
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We aim to start pilot data collection in 2018.
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Acknowledgements• Professor Diana Sarfati.
• My Fellowship Advisory Group.
• The Health Research Council.
• The Cancer Society of NZ.
• Centre for Men’s Health.
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Life.(Not to scale)
Genetic Exposures + Gene:Environment Interactions…
Birth
Pre-Natal Exposures Post-Natal Exposures
(…+Environment:Environment Interactions?)
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0.125 0.25 0.5 1 2 4
Asian
Pacific
Māori
Adjusted relative risk of condition (ref=Euro/Other)
Cryptorchidism
TC
Source: Gurney, et al. (2015). Andrology, Accepted and In Press.
Relative risk of TC and Cryptorchidism in NZ
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“Future research in this area should be focused on the
genetic and environmental exposures that could disrupt normal testicular descent.”1
1 Gurney, et al. (2013). The Journal of Urology, 190, p1852-1857.
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0.125 0.25 0.5 1 2 4
Asian
Pacific
Māori
Adjusted relative risk of condition (ref=Euro/Other)
Hypospadias
Cryptorchidism
TC
Source: Gurney, et al. (2015). Andrology, Accepted and In Press.
Relative risk of TC, Cryptorchidism and Hypospadias
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“Our observations suggest…that the exposures that drive the development of hypospadias
differ to those that that drive the development of cryptorchidism
and/or testicular cancer.”1
1 Gurney, et al. (2015). Andrology, Accepted and In Press.
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