Kidney Cancer Overview -

Incidence, Causes and Risk

Factors

Dr. Paul Nathan

Mount Vernon Cancer Centre
UK

May 2010 KCA Patient - Survivor Seminar

 Kidney Cancer
• What is cancer?
• Different types of Kidney Cancer
• Renal Cell Carcinoma
– Epidemiology
– Causes
– Sub types

May 2010 KCA Patient - Survivor Seminar

 Cells
• We’re made up of them
• Originate from pluripotent stem cells
(able to turn into any type) & then
differentiate
• Normally proliferation, differentiation,
invasion tightly controlled

May 2010 KCA Patient - Survivor Seminar

May 2010 KCA Patient - Survivor Seminar
 Under normal circumstances….

• Cell cycle tightly controlled

• Fidelity of DNA replication v. high
• Errors undergo programmed cell death
(apoptosis)

May 2010 KCA Patient - Survivor Seminar

 Cancer cells….
• Lose proliferation control
• Lose balance between proliferation &
apoptosis
• Invade
• Stimulate angiogenesis (new blood
vessel formation)

May 2010 KCA Patient - Survivor Seminar

May 2010 KCA Patient - Survivor Seminar
 All cancer cells within a
cancer are not exactly the
same
• Mutations in quality control machinery
allows genetic errors to accumulate
• Mutations in cell death control allows
cells to survive even when damaged

• Cancer populations therefore

heterogeneous
May 2010 KCA Patient - Survivor Seminar
May 2010 KCA Patient - Survivor Seminar
 Implications of Heterogeneity

• Likely that some cells survive post treatment

• Underpins rationale for combination treatment
• Underpins rationale for anti-angiogenic
treatment
• However in most cancers, despite
combination treatment, some cells survive
– In which case it may be better to use therapies
sequentially

May 2010 KCA Patient - Survivor Seminar

May 2010 KCA Patient - Survivor Seminar
 Cancer and Darwin
• Cancer cells equipped for natural selection
• Intrinsically highly genetically unstable
• Infinitely variable
• Survive despite huge selection pressures

• Which is why metastatic disease is so difficult

to treat….

May 2010 KCA Patient - Survivor Seminar

May 2010 KCA Patient - Survivor Seminar
May 2010 KCA Patient - Survivor Seminar
 Table 2.1: Number of deaths and mortality rates of kidney
cancer, UK, 2005
England Wales Scotland N.Ireland UK
Deaths
Males 1,849 111 193 51 2,204
Females 1,094 80 168 34 1,376
Persons 2,943 191 361 85 3,580
Crude rate per 100,000 population
Males 7.5 7.7 7.9 6.1 7.5
Females 4.3 5.2 6.4 3.9 4.5
Persons 5.9 6.4 7.1 5.0 6.0
Age-standardised rate (European) per 100,000 population
Males 6.2 5.9 6.3 5.9 6.1
CI 95% 5.9 6.4 4.8 7.0 5.4 7.2 4.3 7.5 5.9 6.4
Females 2.8 3.2 4.0 3.1 2.9
CI 95% 2.6 2.9 2.5 3.9 3.4 4.6 2.1 4.2 2.8 3.1
Persons 4.3 4.4 5.0 4.3 4.4
CI 95% 4.1 4.5 3.8 5.1 4.5 5.5 3.4 5.2 4.2 4.5

May 2010 KCA Patient - Survivor Seminar

 The 20 most common causes of death from cancer, UK, 2008

May 2010 KCA Patient - Survivor Seminar

Figure 1.2: Numbers of new cases and age specific incidence rates,
by sex, kidney cancer, UK 2004
700 80
Male cases Female cases

Rate per 100,000 population

600 Male rates Female rates

60
Number of cases

500

400
40
300

200
20
100

0 0

85+
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
0-4
5-9

Age at diagnosis

May 2010 KCA Patient - Survivor Seminar

May 2010 KCA Patient - Survivor Seminar
 Figure 1.8: Age standardised (European) incidence rates, kidney cancer, by
sex, UK, 1993-2004
15
Rate per 100,000 population

males females persons

10

0
1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004
Year of diagnosis

May 2010 KCA Patient - Survivor Seminar

 Figure 1.3: World age-standardised incidence rates for kidney cancer, selected countries,
2002 estimates

Czech Republic

Estonia

USA

France

Canada

Australia

Denmark

United Kingdom

Japan

Brazil Males

Ethiopia
Females
China

Egypt

Indonesia

India

0 5 10 15 20 25
May 2010 Rate per
KCA Patient 100,000 Seminar
- Survivor population
 Causes of Renal Cell
Carcinoma
• Age, Sex
• Obesity
– Accounts for 25% of cases
• Smoking
– Accounts for 10-15% of female and 20-30% of
male cases
• Hypertension
• Renal cystic disease. Dialysis
• Family history - siblings / children?
• Familial
May 2010 KCA Patient - Survivor Seminar
 Sub-types of RCC
• Clear cell (conventional) 70-75%
• Papillary 10-15%
– Type 1
– Type 2
• Chromophobe < 5%
• Collecting Duct <1%
– Medullary

May 2010 KCA Patient - Survivor Seminar

 Inherited Forms of RCC

May 2010 KCA Patient - Survivor Seminar

HIF regulated
genes

Semenza, Nature Reviews Cancer 3 (10) 2003

Siemann group, Eur J Cancer
 Summary
• Cancer cell evolution can’t fight successful
surgery - early diagnosis
• Modifiable risk factors - smoking & obesity
• Improved understanding of underlying genetic
lesions will allow
– Optimal use of available drugs
– Discovery of new advances

May 2010 KCA Patient - Survivor Seminar

 Familial vs Sporadic Cancers
• 2 copies (allelles) of every gene
• Generally need both copies mutated to
have major effect upon function
• Inherited cancers - mutated allelle passed
on to next generation
– Only need a single acquired mutation
– Familial cancers therefore in younger adults

May 2010 KCA Patient - Survivor Seminar