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Telomere dan kematian akibat kanker 

Telomeres membentang pendek pada nukleotida berulang yang melindungi ujung kromosom . Dalam sel-sel somatik , urutan pelindung ini menjadi lebih pendek dengan masing-masing replikasi seluler sampai panjang kritis tercapai , yang dapat memicu kematian sel . Pada akhir studi mereka , para penulis menyimpulkan , " Kami berspekulasi bahwa telomere yang panjang mungkin merupakan bagi manfaat kelangsungan hidup sel-sel kanker , sehingga pembelahan sel yang mengarah ke beberapa angka kematian kanker yang tinggi . "...read more

Telomeres and
cancer mortality: The long and the short of it

Date:

April 10, 2015

Source:

Oxford University
Press USA

Summary:

Telomeres are short
stretches of repeated nucleotides that protect the ends of chromosomes. In
somatic cells, these protective sequences become shorter with each cellular
replication until a critical length is reached, which can trigger cell death.
At the conclusion of their study, the authors conclude, "We speculate that
long telomeres may represent a survival advantage for cancer cells, allowing
multiple cell divisions leading to high cancer mortality."

.......................

telomeres are short
stretches of repeated nucleotides that protect the ends of chromosomes. In
somatic cells, these protective sequences become shorter with each cellular
replication until a critical length is reached, which can trigger cell death.

In actively replicating cells such as germ cells, embryonic stem cells, and
blood stem cells of the bone marrow, the enzyme telomerase replenishes these
protective caps to ensure adequate replication. Cancer cells also seem to have
the ability to activate telomerase, which allows them to keep dividing
indefinitely, with dire consequences for the patient. However, according to a
study published April 10 in theJNCI: Journal of the National Cancer
Institute, the extent to which cancer cells can utilize telomerase may
depend on which variants of the genes related to telomerase activity are
expressed in an individual's cells.

Telomere shortening is an inevitable, age-related process, but it can also
be exacerbated by lifestyle factors such as obesity and smoking. Thus, some
previous studies have found an association between short telomeres and high
mortality, including cancer mortality, while others have not. A possible
explanation for the conflicting evidence may be that the association found
between short telomeres and increased cancer mortality was correlational but
other factors (age and lifestyle), not adjusted for in previous studies, were
the real causes. Genetic variation in several genes associated with telomere
length (TERC, TERT, OBFC1) is independent of age and lifestyle. Thus, a genetic
analysis called a Mendelian randomization could eliminate some of the
confounding and allow the presumably causal association of telomere length and
cancer mortality to be studied.

To perform this analysis, Line Rode, M.D., Ph.D., of the Department of
Clinical Biochemistry and The Copenhagen General Population Study, Herlev
Hospital, Copenhagen University Hospital, Herlev, Denmark, and colleagues, used
data from two prospective cohort studies, the Copenhagen City Heart Study and
the Copenhagen General Population Study, including 64,637 individuals followed
from 1991-2011. Participants completed a questionnaire and had a physical
examination and blood drawn for biochemistry, genotyping, and telomere length
assays.

For each subject, the authors had information on physical characteristics
such as body mass index, blood pressure, and cholesterol measurements, as well
as smoking status, alcohol consumption, physical activity, and socioeconomic
variables. In addition to the measure of telomere length for each subject,
three single nucleotide polymorphisms of TERC, TERT, and OBFC1 were used to
construct a score for the presence of telomere shortening alleles.

A total of 7607 individuals died during the study, 2420 of cancer. Overall,
as expected, decreasing telomere length as measured in leukocytes was
associated with age and other variables such as BMI and smoking and with death
from all causes, including cancer. Surprisingly, and in contrast, a higher
genetic score for telomere shortening was associated specifically with
decreased cancer mortality, but not with any other causes of death, suggesting
that the slightly shorter telomeres in the cancer patients with the higher
genetic score for telomere shortening might be beneficial because the uncontrolled
cancer cell replication that leads to tumor progression and death is reduced.

The authors conclude, "We speculate that long telomeres may represent
a survival advantage for cancer cells, allowing multiple cell divisions leading
to high cancer mortality."







Story Source:

The above story is based on materials provided by Oxford
University Press USA.Note: Materials may be edited for content and length.







Journal Reference:

1.    L. Rode, B. G. Nordestgaard, S. E.
Bojesen. Peripheral Blood Leukocyte Telomere Length and Mortality Among
64 637 Individuals From the General Population. JNCI Journal of the
National Cancer Institute, 2015; 107 (6): djv074 DOI: 10.1093/jnci/djv074

http://www.sciencedaily.com/releases/2015/04/150410165312.htm

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