The incidence of testicular cancer in western countries has increased
steadily in the past 40-50 years. The etiology of testicular cancer
is not well understood, but there is sufficient evidence to postulate
a link with endocrine modulating substances.
Testicular cancer is a rare cancer, with an age-adjusted incidence of
4.2/100,000 in Canada. This accounts for 1.1% of all malignant neoplasms
in Canadian males. Despite the low overall incidence of testicular cancer,
it is the most common malignancy among young men, 25-34 years old. Testicular
cancer varies notably with race, with incidence rates about threefold
higher in Caucasians compared to African Americans in the US.
The incidence rate of testicular cancer has been increasing since
the middle of the 20th century in many western countries, including
Canada, the United States, the Nordic Countries, and Britain. The trend
has been especially rapid in eastern European countries such as Slovenia.
Countries with a sufficiently long period of cancer registration, such
as Denmark, document this trend back to the first half of the 20th century.
Despite the increase in testicular cancer in many western countries,
the age-adjusted incidence of testicular cancer is low in all populations
of the world. The lowest rates have been observed in Asian populations,
African Americans, and black populations in general. The incidence rate
in Denmark is in the order of 8 per 100,000, while in Japan and China
and in African Americans, the incidence rate is on the order of 1 per
100,000. While the increase in testicular cancer incidence is an important
cause of morbidity in young males, testicular cancer is one of the most
curable of all solid neoplasms. The five year survival rate has increased
during the last 30 years from 63% to over 90%. The present case fatality
rate is 10-15 percent, and even in metastatic cases, cure rates are
as high as 80 percent.
the data: The etiology of testicular cancer is poorly understood.
Most of the established risk factors are related to in utero events
including: cryptochidism or maldescendent testicles, carcinoma in situ
and exposure to estrogen in utero. These established risk factors suggest
that hormonal exposures may affect testicular cancer risk, particularly
exposure to estrogen in utero. However, the exact nature of the link
between estrogen exposure and testicular cancer is unclear. It has been
suggested that exposure to high levels of estrogen in utero results
in the development of carcinoma in situ, which appears to be a precursor
of testicular cancer. The associations between estrogen exposure and
testicular cancer include an increased risk associated with: nausea
in pregnancy resulting from high endogenous estrogen levels, DES exposure,
and non-specified hormone use in pregnancy. In addition to these exposures,
endogenous maternal estrogen levels are higher in first pregnancies
as compared to subsequent ones and several studies have found that children
of mothers with high parity have a decreased risk of testicular cancer
when compared to male children of nulliparous mothers. Twin studies
have observed that dizygotic twin pregnancies have higher maternal hormones
levels than monozygotic pregnancies. As a result, dizygotic twins have
a higher risk of testicular cancer than monozygotic twins. Finally,
maternal smoking may be protective of testicular cancer, possibly be
due to increased turnover of estrogen in cigarette smokers. It would
appear that estrogen has an important role in the etiology of testicular
cancer, and warrants further study.
cell tumors in adults are a well described cytogenetic entity. They
have a chromosome number in the triploid range, and are characterized
by specific chromosomal gains at chromosomes 7, 8, 12, 21, and X, and
by specific chromosomal losses at chromosomes 11, 13, and 18. A non-random
genetic alteration has been localized to i(12p). Studies have shown
that 80% of testicular tumors have one or more copies of i(12). It would
seem that isochromosome 12p is the recurrent structural chromosomal
abnormality of these tumors. It has been estimated that 33.4% of all
cases of testicular cancer are in individuals with the malignant genotype,
assuming it is a recessive trait.
Other risk factors
of testicular cancer that have been examined include: occupation, chemical
exposure, radiation exposure, socio-economic status, and diet. Recent
studies regarding testicular cancer risk and diet have pointed to a
risk associated with dairy products. In addition to fats, protein and
calcium, milk and dairy products contain considerable amounts of female
sex hormones such as estrogens and progesterone. These hormones are
a result of the fact that present-day milk is produced from pregnant
cows. A significant elevated risk of testicular cancer has been linked
to exposure to polyvinyl chloride; however this has yet to be confirmed.
evidence: The types of testicular cancer commonly found in humans
are preceded by atypical intratubular germ cells termed CIS (carcinoma
in situ) which is extremely rare in laboratory animals. Until recently,
experimental animal models appropriate for extrapolation to humans were
lacking. CIS like lesions have been induced in rabbits exposed in utero
and/or in infancy to the toxicants octylphenol, p,p'- DDT/DDE or zeranol.
These results illustrate the potential relevance of the rabbit as a
model for this type of cancer in humans. However, validated animal models
for germ cell (testicular) tumours observed in man currently do not
Despite the absence of direct human evidence, the role of man-made chemicals
can contribute to the pathogenesis of testicular cancer development
by the estrogenetic/anti-androgenetic effect of the hormones on the
testes. However, the hormonally active environmental chemicals involved,
the pathways in which they act, and their associated risk of cancer
The etiology of testicular cancer remains unknown. However, many of
the risk factors point towards a hormonal mechanism of carcinogenesis.
Currently there is a lack of direct evidence regarding the link between
environmental endocrine disrupting chemicals and testicular cancer risk.
As well, the link between estrogenic or anti-androgenic compounds and
testicular cancer has not yet been examined. In addition, the current
lack of a suitable animal model prevents definitive conclusions on the
role of hormonally active environmental chemicals on testicular cancer