Xeroderma Pigmentosum (XP) is a genetic disorder regarding DNA repair (1). It
causes a deficiency in the body’s ability to remove damage caused by ultraviolet light (1).
Therefore, patients have a much higher risk of developing skin cancers. As stated by
Yuko Hirai et al. in “Heterozygous individuals bearing a founder mutation in the XPA
DNA repair gene comprise nearly 1% of the Japanese population,” XPA contributes to
the development of XP. It is one of eight proteins that work together to repair UV-
induced DNA damage (1).
During the process of nucleotide excision repair of UV-induced DNA damage, the
XPA protein is specifically responsible for damage verification, while XPB is recognized
as a 3’-5’ helicase (1). XPC and XPE are responsible for binding damage, while XPD is
a 5’-3’ helicase (1). XPF and XPG are a 5’ and 3’ nuclease, respectively (1). There is
one variant form of XP known (1). Patients with this variant form are defective in repair
due to a mutation in the translesional DNA polymerase η (1).
Carriers of the XPA mutation suffer the severest form of XP (1). Symptoms of
patients with group A XP include cutaneous lesions, and changes in the peripheral
nervous system (2). Symptoms of XP in general include hypersensitivity to sun
exposure, including blistering and pain that occurs immediately after sun exposure (2).
Acute sunburn, constant redness, or inflammation of skin when exposed to sunlight are
also common symptoms of this disorder (2). Other symptoms include discoloration,
weakness, and scarring of the skin (2).
XPA is the most common form of XP in Japan (2). Over half of the Japanese XP
patients are homozygous for a founder mutation in the XPA gene (1). A founder
mutation is a mutation derived from a single ancestor (1). There are about 1 million
carriers of the XPA founder mutation in the Japanese population (1). The XPA founder
mutation is a G to C base-change at the 3’ splice acceptor site of intron three (1). This
mutation results in no detectable protein production (1).
The objective of this paper was to find whether or not heterozygous carriers for
mutations in DNA repair genes are at high risk to cancer (1). The study subjects were
randomly selected offspring of subjects used in another study aimed at determining the
genetic effects of radiation in the offspring of atomic bomb survivors (1). Blood samples Johnson 2
were used in the present study from only one sibling in each family (1). The source of
DNA for analysis was archival collections of blood lymphocytes that were stained with
Giemsa and mounted as cytogenic slides (1).
These subjects were selected from RERF of children born to parents exposed to
radiation and control subjects born to parents who were not exposed to radiation (1).
RERF is the Radiation Effects Research Foundation (3). The frequency of XP patients in
Japan is over ten times higher than that of Western countries (1). The proportion of these
patients in group A, the severest form, is almost twice as high as in other countries (1).
There is no reason, however, to assume that XP patients in Japan might be a result of the
atomic bombs dropped in Hiroshima and Nagasaki because there is a common mutation
(founder mutation) more than half of the Japanese XP patients (1). The study showed
that the frequency of XPA heterozygotes with the founder mutation was 0.88% (1 in 113)
in the Hiroshima and Nagasaki subjects.
Hirai et al. used PCR-RFLP analysis to amplify 61 bp DNA and then subjected it
to restriction enzymes (1). DNA from XPA heterozygous carriers would show three
bands after gel electrophoresis (1). When it was assumed that a sample had the mutation,
PCR-RFLP was repeated using the same DNA for confi