Jack: Hi, all.
In this lecture,
we'll be discussing the epidemiology of kidney cancer.
The goals of this lecture
are to review the anatomy and function of the kidney.
to describe the global burden of kidney cancer,
and look at trends and differences in mortality rates.
We'll also define renal cell carcinoma
and describe risk factors for renal cell carcinoma.
So to begin with, to give an overview of the kidney,
the human kidneys are paired organs
that excrete waste products and metabolism,
regulate the body's concentration of water and salt,
maintain the acid-base balance of the blood,
regulate blood pressure, and secrete important hormones,
including erythropoietin, renin, and prostaglandins.
Urea is the most abundant
of the nitrogen-containing waste products
created by the kidneys.
Urea is formed for ammonia or ammonia acids
by a series of reactions known as the urea cycle,
which occurs primarily in the liver.
The basic functional unit of the kidney is the nephron.
Each kidney contains up to 1 million nephrons
that carry out the essential functions of the kidney.
Each nephron receives unfiltered blood
from an afferent or arterial,
which divides into capillaries of the glomerulus.
The glomerulus filters urea and other waste products
from the blood.
In 2012, 337,860 new cases were detected,
and 143,369 deaths were attributed to kidney cancer.
The incidence and mortality
have increased steadily in the past two decades.
And while the arising incidence rates
may be partly attributable to improvements
in imaging tech techniques,
better detection does not explain
the worldwide increase in mortality.
During 2012, the annual incidence rates in populations
of developed nations, 10 per 100,000 for men
and five per 100,000 for women were five-fold higher
than corresponding rates in low and middle income countries,
which were two per 100,000 for men
and one per 100,000 for women.
Mortality rate shows similar pattern.
Such differences are largely attributable to under-reporting
due to lack of diagnostic imaging and detection
in low- and middle-income countries.
Differential effects of lifestyle
and environmental exposures may also be contributing.
Historically, the cross triad of clinical signs,
flank pain, hematuria, and palpable mass in a patient
usually led to the detection of a large tumor of the kidney
at a late stage of development.
Such tumors have often metastasized to other anatomic sites
by the time they were diagnosed,
making treatment difficult and prognosis poor.
In the current practice of medicine,
kidney tumors are often detected incidentally
at a relatively early stage of development
during imaging studies of the abdomen for other conditions.
As with all forms of cancer,
early detection of kidney cancer is essential
for successful therapy and prolonged patient survival.
Kidney tumors detected in an early stage
often respond well to treatment,
and as a consequence, survival rates have improved
and mortality rates have stabilized or declined
in many developed nations of the world.
Nevertheless, in less developed nations
without sophisticated methods of early detection,
the upward trend in mortality is continuing.
In 2020, there was an age-standardized incidence
of 4.6 per 100,000 people overall.
In men, that incidence was 1.8 per 100,000.
While in women it was 3.2 per 100,000.
The overall mortality rate was 1.8 per 100,000.
While in men, that rate was 2.5 per 100,000,
and 1.2 per 100,000 in women.
There's several different kinds of kidney cancer.
Renal cell carcinoma arises from epithelial cells
that line the renal tubules,
and is the most common type of kidney cancer,
accounting for approximately 85 to 90%
of all malignant kidney tumors.
These cells normally secrete a variety
of vasoactive and regulatory hormones.
Wilms' tumor, named after the German surgeon, Max Wilms,
who first described it,
counts for about 5% of malignant kidney tumors.
This tumor occurs almost exclusively in children
under the age of 10 years, usually before the age of five.
And Wilms' tumor are comprised
of mixed stromal and epithelial cells
with a board of configurations
of renal, glomeruli, and tubules.
Transitional cell carcinomas arising from epithelial cells
of the junction of the renal pelvis and the ureter
constitute 5 to 10% of malignant kidney tumors.
Microscopically, transitional cell carcinomas
of the renal pelvis are similar to urothelial carcinomas
of the urinary bladder.
These transitional epithelial cells are intermediate
between flat squamous cells and tall columnar cells.
There's a number of risk factors for renal cell carcinoma.
Epidemiologic studies have clearly established
that each of these factors
has an etiologic link with renal cell carcinoma.
Specific dietary factors
and certain other environmental factors
have also so shown effects in some studies.
A notable finding for molecular analysis
of renal cell tumors or a clear cell subtype
is the frequent presence of abnormalities
in the von Hippel Lindau gene,
a tumor suppressor gene with pleiotropic
are multiple effects on tumor growth and development.
Renal cell carcinoma occurs in a male to female ratio
of approximately 1.6:1 in most populations studied.
Recent analysis of the U.S. Surveillance, Epidemiology,
and End Results, or SEER database shows that men present
with significantly higher and higher grade
are larger and higher grade tumors than women.
Women have a slightly higher
five-year survival rate than men.
And men have higher levels of exposure to tobacco
and other toxic compounds than women.
Women are also traditionally more health conscious than men.
The association of smoking in renal cell carcinoma
was examined in a meta-analysis
of 24 epidemiologic investigations,
19 case control studies, and five cohort studies.
Combined estimates of relative risk forever smokers
compared to never smokers were 1.38 for all subjects,
1.54 for men, and 1.22 for women.
There were significant dose responses and the risk
with increasing intensity of smoking
in both men and women, and significant risk reductions
were evident in former smokers.
Two case control studies found evidence
that exposure to environmental smoke
significantly increase the risk
of developing renal cell carcinoma,
but further studies will be needed
to confirm this association.
Regulation of blood pressure
is an important kidney function.
And as such, hypertension has been extensively studied
as a risk factor
for the development of renal cell carcinoma.
Several recent epidemiologic studies of hypertension
and renal cell carcinoma in different populations
show reasonable consistency in revealing an association.
Nevertheless, whether hypertension is a cause
or an effect of this malignancy
remains a topic of high controversy.
A study in 2000 examined the health records
of 363,992 Swedish men
who underwent at least one fiscal exam during 1971 to 1992,
and were followed until death
or the end of the study in 1995.
In this study, cases of kidney cancer
were identified through cross linkage of data
within nationwide Swiss Cancer Registry,
or Swedish Cancer Registry.
Results revealed that obesity and hypertension
independently increased the risk
of developing renal cell carcinoma,
but not transitional cell carcinoma,
whereas smoking was a risk factor
for both forms of kidney cancer.
Another study published in 2005
examined the association between death from kidney cancer
and baseline hypertension in a large cohort of Korean men
who were studied from 1992 to 2001.
In this study,
hypertension was found to significantly increased the risk,
and the risk was particularly high among cigarette smokers.
Finally, in a 2005 study,
hypertension was examined
in relation with thiazide use, body mass index,
weight change, and smoking.
Those all were considered as risk factors
for renal cell carcinoma in prospective cohorts in the U.S.
After adjusting for other variables,
hypertension significantly increased the risk
of cancer development in both women and men.
Risk increases were also noted
for obesity and chronic smoking,
but there was no increase with thiazide use.
What's clear from these numerous studies
is that hypertension is independently associated
with a significant increase
in the risk of developing renal cell carcinoma
in both men and women.
What is not yet clear is the sequence of pathogenesis.
Does malignant transformation induced changes
in renin and other vasoactive substances in the kidney
that increase blood pressure?
Or does an increase in blood pressure
cause malignant transformation?
Since type 2 diabetes is ideologically linked
to chronic diseases of the kidney,
like nephrosis and nephritis,
it's logical to examine the association
between diabetes and kidney cancer.
Across numerous studies, individuals with diabetes
were at increased risk for the development of kidney cancer
compared to those without diabetes.
However, there was statistically significant heterogeneity
among studies and the association with diabetes
was stronger in women than men.
Additional studies designed to assess the time interval
both between the onset of diabetes
and the development of kidney cancer are necessary.
Renal cell carcinomas occasionally occur
in a familial setting
in association with certain genetic abnormalities.
However, only a small fraction of cases, or about 4%,
report a positive family history of kidney cancer.
Familial cases often develop multifocal
and or bilateral tumors at a relatively early age.
Among the heritable cancer syndromes,
the most important are the von Hippel Lindau syndrome
and the Birt-Hogg-Dube syndrome.
The von Hippel Lindau syndrome
is a rare autosomal dominant cancer syndrome,
with a prevalence rate of about one in 36,000 individuals.
The syndrome is caused by a mutant tumor suppressor gene
called the von Hippel Lindau gene, or the VHL gene.
Approximately 1/3 of patients who carry a mutant VHL gene
develop clear cell renal carcinoma.
Birt-Hogg-Dube syndrome is a rare
autosomal dominant syndrome that has been identified
in about 50 families worldwide.
This syndrome is characterized by renal cancer.
renal and pulmonary cysts,
and benign tumors of the hair follicles.
It's caused by mutations in the folliculin gene,
or the FLCN, a tumor suppressor gene
located in the short arm of chromosome 17.
Occupational exposures can also play a role
in the development of renal cell carcinoma,
and we see here that asbestos, cadmium,
and petroleum products, and dry cleaning solvents
all have an elevated risk of development of RCC.
We also see that there's synergism
involving environmental exposures in some studies.
A combination of cadmium exposure
and cigarette smoking, for example,
increase the risk of renal cell carcinoma
more than four-fold.
Results of studies of renal cell carcinoma
and heavier long-term use of analgesics are inconsistent.
One study looked at 440 cases of renal cell carcinoma,
spouses of 151 cases, and 691 control subjects.
This study found there was no significant excess risk
observed with regular use of aspirin, acetaminophen,
or combinations of these agents.
Acquired cystic kidney disease
develops in approximately 50% of patients
who are maintained on chronic hemodialysis
and peritoneal dialysis for kidney failure.
A major complication of this condition
is the development of renal cell carcinoma.
Follow up studies of patients
with acquired cystic kidney disease
suggests that their risk of developing renal cell carcinoma
is 50-fold higher than in the general population.
Careful surveillance of dialysis patients
by periodic ultrasonography and computerized tomography
is recommended for the early detection of such tumors.
Finally, the profile of risk factors
associated with the development
of transitional cell carcinomas of the renal pelvis
is essentially the same as for transitional cell carcinomas
of the urinary bladder.
The dominant risk factors,
chronic exposure to tobacco smoke,
which has been found to elevate the risk
two- to three-fold compared to non-smokers.
Carcinogenesis associated with smoking
is primarily the result of aromatic amines and oral amines
present in cigarette smoke.
A number of environmental and occupational factors
increase the risk,
including occupational exposure to aerial amines
and other compounds in intermediates
in the synthesis of azo dyes and pigments
used in the textiles, printing, plastic, rubber,
and cable industries.
Long-term exposure to these compounds
among workers in the industries
increase the risk by about 50%.