Study ties telomere-controlling gene to breast, ovarian cancers

March 30, 2013 | by Shawn Le

While high school biology has hammered in the all too familiar double-helix shape of DNA, with chromosomes it may be easier to visualize them as a pair of shoelaces, since its telomeres are the genetic equivalent of laces’ plastic caps that keep them from fraying apart at the tips.

Telomeres help maintain chromosomes' integrity during replication and protein production, but a few variations in the TERT gene can causes damaging changes that lead to cancer, City of Hope researchers found. Telomeres help maintain chromosomes' integrity during replication and protein production, but a few variations in the TERT gene can causes damaging changes that lead to cancer, City of Hope researchers found.

Likewise, telomeres act as protective caps at the ends of chromosomes by maintaining their integrity. But as genes work at replicating themselves or producing proteins, the telomeres get worn down, and the cell can breakdown. Normally, these broken cells are cleared away by the body’s immune system to make way for healthy new cells. But if it lingers around, the fraying gene in the worn down cell can cause a great amount of damage, triggering processes that can make the cell cancerous.

Aware of this malfunction's destructive impact, researchers from the Collaborative Oncological Gene-environment Study (COGS) consortium, are studying how the gene regulating telomeres — called TERT — contributes to the development of breast and ovarian cancers.

Their findings were published on March 27 in the journal Nature Genetics. COGS members Jeffrey Weitzel. M.D., chief of City of Hope’s Division of Clinical Cancer Genetics, and Susan Neuhausen, Ph.D., the Morris & Horowitz Families Professor in Cancer Etiology and Outcomes Research at City of Hope, contributed to this paper.

Previous studies had demonstrated how single-nucleotide polymorphisms – one amino acid pairing variation in a gene – were associated with some breast and ovarian cancers. Variations are sometimes mistakenly introduced into genes when they replicate. While one pairing out of order rarely shuts down the cell, enough single-nucleotide polymorphisms stacked together may lead to cancer.

The team analyzed the records of more than 158,000 participants in 52 Breast Cancer Association Consortium studies, 43 Ovarian Cancer Association Consortium studies and 45 Consortium of Investigators of Modifiers of BRCA1 and BRCA2 studies. They found that in the TERT gene:

  • Single-nucleotide polymorphisms in two specific areas were strongly associated with telomere length.
  • Polymorphisms in two areas among BRCA mutation carriers and three areas in the general population were linked with breast cancer risk.
  • Two polymorphisms were associated with ovarian cancer risk.

The authors write in their paper that “this study provides definitive evidence for genetic control of telomere length by common genetic variants in the TERT locus.” Additionally, they write: “Our results show that the relationships between TERT genotype, telomere length and cancer risk are complex and that the TERT locus may influence cancer risk through multiple mechanisms.”

In other words, the team has found associations between single-nucleotide polymorphisms and telomere length in the risk of disease, but has more research to do to fully understand the relationship.

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