world cancer report - iarc

Syndrome Gene Location Cancer site/cancer
Familial retinoblastoma RB1 13q14 Retinoblastoma,
osteosarcoma
Multiple endocrine neoplasia II RET 10q11 Medullary thyroid carcinoma,
phaeochromo-
cytoma
Multiple endocrine neoplasia I MEN1 11q13 Adrenal, pancreatic
islet cells
Neurofibromatosis type I NF1 17q11 Neurofibromas,
optic gliomas,
phaeochromocytoma
Neurofibromatosis type II NF2 22q2 Bilateral acoustic
neuromas, meningiomas,
cerebral astrocytomas
Bloom syndrome BLM 15q26 Leukaemia, lymphoma
Familial adenomatous polyposis APC 5q21 Colorectal, thyroid
Von Hippel-Lindau VHL 3p25 Renal cell carcinoma,
phaeochromocytoma
Familial Wilms tumour WT1 11q Wilms tumour (kidney)
Xeroderma pigmentosum XP(A-D) 9q, 3p, 19q, Basal cell carcinoma,
15p squamous cell carcinoma,
melanoma (skin)
Fanconi anaemia FAC 16q, 9q, 3p Acute leukaemia
Li-Fraumeni syndrome p53 17p13, Breast and adrenocortical
carcinomas, bone and
soft tissue sarcomas,
brain tumours, leukaemia
Cowden syndrome PTEN 10q22 Breast, thyroid
Gorlin syndrome PTCH 9q31 Basal cell carcinoma
X-linked proliferative disorder XLP Xq25 Lymphoma
Peutz-Jeghers syndrome LKB1 19p Breast, colon
Ataxia telangiectasia ATM 11q22 Leukaemia, lymphoma
Table 2.20 Inherited cancer syndromes caused by a single genetic defect. The lifetime risk of cancer is
high. There are usually recognizable phenotypic features that make the syndromes easy to identify clinically.
Although most cancers arise through
somatically acquired mutations (which are
found uniformly only in relevant tumour
cells), about 5% of all cancers can be attributed
to inherited gene alterations which are
common to every cell in an affected individual.
Such a genetic change may be present
in, and hence inherited from, one parent or
may have occurred in a germ cell (egg or
sperm cell) before fertilization, and may, in
72 The causes of cancer
turn, be passed on to the next generation.
These alterations, in every cell, constitute a
partial commitment to cancer which may be
completed either by random processes or
as a result of environmental insults. This
theory of why tumour development preferentially
occurs in individuals with a genetic
predisposition was first proposed by Alfred
Knudson in 1971 in the context of a childhood
eye tumour, familial retinoblastoma [1]
Fig. 2.66 Child with retinoblastoma, a malignant
tumour of the eye, which arises from retinal germ
cells. In the familial form it is caused by an autosomal
dominant mutation of the retinoblastoma
gene.
Fig. 2.67 Patient with xeroderma pigmentosum, a
rare inherited (autosomal recessive) disease,
exhibiting spots of hyperpigmentation in sunexposed
portions of the skin, which are prone to
develop into multiple skin cancers. The disease is
caused by mutations in genes involved in DNA
repair.
(Figs. 2.65, 2.66). In general, inherited
forms of cancer occur at an earlier age than
sporadic or environmentally-caused
tumours. Thus although only a relatively
small fraction of all cancers are attributable
to inherited mutations in cancer susceptibility
genes, such “germline” alterations
account for a significant fraction of cancers
occurring at young ages. It is also likely that
individual differences in the ability to detoxify
or metabolize carcinogens (Carcinogen
activation and DNA repair, p89) or regulate
levels of hormones (Reproductive factors
and hormones, p76) are under some degree
of genetic control. Both of these forms of
variation would modify the effects of environmental
exposures and the consequent
cancer risk.