A gene important in skin tanning has been linked to higher
risk for testicular cancer in white men, according to a
study. Nearly 80 percent of white men carry a variant form
of this gene, which increased risk of testicular cancer up
to threefold in the study. The
team suspected that variations in a gene pathway controlled
by the tumor suppressor gene p53 could have both positive
and negative effects on human health.
“Gene variations
occur naturally, and may become common in a population if
they convey a health benefit,” said the author
“It appears that this particular variant could help
protect light-skinned individuals from UV skin damage, like
burning or cancer, by promoting the tanning process, but it
permits testicular stem cells to grow in the presence of DNA
damage, when they are supposed to stop growing.” He
explained that p53 stimulates skin tanning when ultraviolet
light activates it in the skin. It then must bind a specific
sequence of DNA located in a gene called the KIT ligand
oncogene (KITLG), which stimulates melanocyte production,
causing the skin to tan. To conduct the analysis co-author
and lead bioinformatics scientist led a data mining
expedition to sieve through many different data sets. The
team selected possible leads from the intersection of more
than 20,000 p53 binding sites in the human genome, 10
million inherited genetic variations genotyped in the 1000
Genomes Project, and 62,000 genetic variations associated
with human cancers identified in genome-wide association
studies (GWAS). These data sets were gathered through joint
efforts of thousands of researchers from around the world.
“In the end, one variant in the p53 pathway was strongly
associated with testicular cancer, but also, surprisingly,
displayed a positive benefit that is probably related to
tanning that has occurred as humans evolved. Co-author
noted. The group performed complex experiments to confirm
the molecular mechanism that linked the variant with cancer
and tanning. “White males with a single nucleotide variation
in KITLG, called the G allele, have the highest odds of
having testicular cancer. In fact, the twofold to threefold
increased risk is one of the highest and most significant
among all cancer GWAS conducted within the past few years,”
researcher said. “The high frequency of this allele in light
skin individuals may explain why testicular cancer is so
much more frequent in people of European descent than those
of African descent.” Researcher said although the G allele
increases testicular cancer risk, it may explain why
testicular tumors are often easily cured with chemotherapy.
“Most other tumors have a mutant p53, but in these
testicular cell tumors, the p53 is functioning properly, and
the drugs used for testicular cancer appear to work in
concert with p53’s tumor suppression function to kill the
cancer cells.”
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