Cancer Risk Predicted by Telomere Length

The caps of DNA at the end of our chromosomes known as telomeres are a crucial part of our biology. Their condition has been linked to aging, cancer and a host of other conditions.

The short and long extremes of telomere length significantly increase cancer risk, according to new University of Pittsburgh research to be presented at the American Association for Cancer Research conference in Washington D.C. today.

Certain cancers are much more likely in people with longer telomeres, while other tumors’ risk factors are greatly increased by the presence of shorter telomeres, said Jian-Min Yuan, the lead author.

“Telomeres and cancer clearly have a complex relationship,” said Yuan in a school statement.

Some 28,000 Chinese people enrolled in the Singapore Chinese Health Study, which began tracking health outcomes and correlated blood samples of the patients in 1993. By the end of 2015, more than 4,000 of the participants had developed cancer.

Short telomeres have previously been linked to cancer. But the longest telomeres carried an even-greater cancer risk for some key tumors, as a key finding of the new work. The longest telomeres overall had 33 percent likelier odds of developing any cancer, more than the shortest telomeres. The longest telomeres also had 66 percent greater odds for lung cancer, 39 percent for breast cancer, 55 percent for prostate cancer, and 37 percent for colorectal cancer. (All the results corrected for the patients’ age, sex, education, and smoking histories).

Pancreatic tumors demonstrated the most dramatic risk increase. The fifth of patients with the longest telomeres had 2.6 times the odds compared with their shortest telomere carrying counterparts.

A U-shaped risk curve still existed, incorporating more cancer risk from the shortest telomeres. The shortest telomeres had 63 percent more risk for stomach cancer, 72 percent increase for bladder cancer, 115 percent greater odds for leukemia than those in the middle of the curve. The longest telomere patients had similar boost on their end of the curve: 55 percent more likely stomach cancer, 117 percent for bladder cancer, and 68 percent for leukemia.

The assessment of telomeres in the Singapore Chinese Health Study was a goal seven years ago – but it took a month to quantify a mere 100 samples, said Yuan. Now the technology has improved to allow some remarkable new observations.

“Not even a decade later, we’ve been able to run nearly 30,000 samples in a year and draw these really robust insights, showing how far technology has come,” said Yuan. “Even more complicated will be linking telomere length to genome-wide analyses, which is on the horizon. We’re on the cusp of gaining a truly remarkable understanding of the complicated biological phenomena that lead to cancer.”

Telomeres are often compared to the plastic tips at the ends of shoelaces, since they keep the strand of DNA together and prevent it from "fraying." But small portions of telomere DNA are lost with each cell division, eventually resulting in cell death. Telomeres continue to be the focus of much research, beyond oncology. Sedentary living means shortening of the telomeres – and more advanced aging, concludes a paper published in January in the American Journal of Epidemiology.