Eble JN, Sauter G., Epstein JI, Sesterhenn IA - iarc

one quarter of kidney cancers in both
sexes are attributable to excess weight.
The association has been reported as
stronger in women than in men in some
but not all studies.
The incidence of RCC is significantly
increased in people with a history of
blood hypertension that is independent
of obesity and tobacco smoking
{458,962,2912}. The association with the
use of diuretics instead is referable to
hypertension, while a small but consistent
excess of RCC has been established
with exposure to phenacetin-containing
analgesics that also cause cancer of the
renal pelvis {1150}.
Parity is a factor that has been investigated
in several studies but results are
discordant {1430}. A real association
would be supported by estrogen-mediated
carcinogenesis that is documented in
animal models. Conversely, it could be a
confounded effect of excess body
weight that is often increased in women
who had many children. Other exposures
that have been addressed are a family
history of kidney cancer {829}, birth
weight {221}, low consumption of fruits
and vegetables {2841} and the use of
antihypertensive drugs other than diuretics.
The significance of these associations
remain however unclear.
Few studies have investigated the
hypothesis that genetic characteristics
may modulate the effect of exposure to
chemical carcinogens. In one study the
effect of tobacco smoking was stronger
in subjects with slow acetylator genotypes
as defined by polymorphisms in
the N-acetyltransferase 2 gene that is
involved in the metabolism of polycyclic
aromatic hydrocarbons {2359}.
Conversely, RCC was not associated
with the glutatione S-transferase (GST)
Fig. 1.02 Age-specific incidence rates of renal cell
cancer in selected countries.
M1 null genotype that is also involved in
the metabolism of several carcinogens,
but was significantly decreased in either
smokers and non-smokers having the
GST T1 null genotype {2544}.
Fig. 1.03 Age-standardized incidence rates of renal cell cancer recorded by population-based cancer registries
around 1995. From D.M. Parkin et al. {2016}.
Clinical features
Signs and symptoms
Haematuria, pain, and flank mass are the
classic triad of presenting symptoms, but
nearly 40% of patients lack all of these
and present with systemic symptoms,
including weight loss, abdominal pain,
anorexia, and fever {870}. Elevation of
the erythrocyte sedimentation rate
occurs in approximately 50% of cases
{634}. Normocytic anaemia unrelated to
haematuria occurs in about 33%
{438,902}. Hepatosplenomegaly, coagulopathy,
elevation of serum alkaline phosphatase,
transaminase, and alpha-2-
globulin concentrations may occur in the
absence of liver metastases and may
resolve when the renal tumour is resected
{1441}. Systemic amyloidosis of the
AA type occurs in about 3% of patients
{2705}.
Renal cell carcinoma may induce paraneoplastic
endocrine syndromes
{1441,2525}, including humoral hypercalcemia
of malignancy (pseudohyperparathyroidism),
erythrocytosis, hypertension,
and gynecomastia. Hypercalcemia
without bone metastases
occurs in approximately 10% of patients
and in nearly 20% of patients with disseminated
carcinoma {736}. In about
66% of patients, erythropoietin concentration
is elevated {2526}, but less than
4% have erythrocytosis {902,2526}.
Approximately 33% are hypertensive,
often with elevated renin concentrations
in the renal vein of the tumour-bearing
Renal cell carcinoma
13