Transcript What are telomeres?

WORLD CANCER
DAY
Presentation by: Amna Ikhlaq, Nageen Zahid, Iqra Soofi, Rafia Ather & Isbah Hussain
(MBBS 3rd Year, UMDC, Faisalabad, Pakistan)
AGE & CANCER
Is cancer a new age disease?
◦ Cancer has existed for as long as humans have, being described by ancient Egyptians
(Edwin Smith Papyrus) and Greek physicians (Hippocrates was first to use the term
cancer) in discovered texts. Researchers have also discovered signs of cancer in a
3,000 year old skeleton.
◦ Advancements in surgery by the likes of Giovanni Morgagni and John Hunter helped
establish that some tumors could be removed by surgical methods.
◦ Invention of microscopy made it easier to study pathology of disease on a cellular level
to further our understanding.
◦ “The simple fact is that more people are living long enough to develop cancer
because of our success in tackling infectious diseases and other historical causes of
death such as malnutrition,” states the Cancer Research UK center. “It’s perfectly
normal for DNA damage in our cells to build up as we age, and such damage can
lead to cancer developing.”
Scientific Evidence
Advancing age is the most important risk factor for cancer overall, and for many
individual cancer types. According to the most recent statistical data from NCI’s
Surveillance, Epidemiology, and End Results program, the median age of a cancer
diagnosis is 66 years.
A similar pattern is seen for many common cancer types. For example, the median age
at diagnosis is 61 years for breast cancer, 68 years for colorectal cancer, 70 years for lung
cancer, and 66 years for prostate cancer.
Why is age a risk factor?
◦ Cancers are age-related, much more frequent in the old than in the young. A University of
Colorado Cancer Center review published July 2 2012 in the journal Oncogene argues
against the conventional wisdom that the accumulation of cancer-causing mutations leads
to more cancer in older people, instead positing that it is the changing features of tissue in
old age that promote higher cancer rates in the elderly.
◦ DeGregori points first to the fact that by the time we stop growing in our late teens, we've
already accumulated a large fraction of the mutations we will have in our lifetimes,
meaning that if cancer were due to reaching a tipping point of, say, five or six mutations, we
should see higher cancer rates in 20-year-olds, as this is when mutation rate is highest.
◦ Second, DeGregori points out that even healthy tissues are full of oncogenic mutations.
"These mutations are many times more common than the cancers associated with them,"
DeGregori says. Simply, more mutations doesn't equal more cancer.
Instead of gathering mutations until they give us cancer, DeGregori says that as
we age, the mechanisms that younger adults use to fight cancer, deteriorate.
Telomeres & Cancer
◦ What are telomeres?
Telomeres are structures found at the ends of human chromosomes that contain
thousands of repeats of repetitive TTAGGG DNA sequences.
◦ Role of telomerases?
A ribonucleoprotein enzyme complex known as telomerase maintains telomere length in
cancer cells by adding TTAGGG repeats onto the telomeric ends, compensating for the
normal shortening of telomeres in all dividing cells.
◦ Correlation to cancer
Since telomere shortening is strongly correlated with an increased risk of cancer during
aging and chronic disease, the scientific literature suggests that the loss of telomere
capping function contributes to the induction of chromosomal instability and cancer
initiation process.
In addition to its role in initiating chromosomal instability, telomere dysfunction gives rise
to cancer by inducing environmental alteration. In vitro evidence has shown that shorter
telomeres directly contribute to the swift progression of the earliest stages of certain
malignancies.
The activation of telomerase represents the most common pathway for stabilizing
telomeres in human cancers. In addition to this, an improvement in telomere capping
function allows proliferation and survival of malignant cells with critically short telomeres.
Targeting telomerase for cancer therapy
As a role of telomerase in the unlimited proliferative potential of cells has been
repeatedly demonstrated, it has been proposed as a potential anticancer target.
In essence, the idea seems exciting, as telomerase is found in different types of human
cancers, while at the same time absent from many normal cells. Thus specific agents that
would target telomerase might kill malignant cells without altering the function of a
majority of normal cells in our body.
◦ A 92-year-old woman became the
oldest woman to ever run a marathon
after finishing the Suja Rock ‘n’ Roll
Marathon in San Diego.
◦ Thompson, who has beaten cancer
twice, runs to raise money for the
Leukemia & Lymphoma Society. Over
more than a decade, she’s raised
more than $90,000 through running 16
marathons.