A new study on the genetics of a large cohort of kidney cancer patients in Europe finds that exposure to plants of the Aristolochia genus (commonly called birthwort, pipevine or Dutchman’s pipe), common throughout the Balkans, is a strong link to kidney cancer, particularly in Romania.
Aristolochia plants have also been suspected of causing a kidney disease known as Balkan endemic nephropathy, affecting people along the tributaries of the Danube River in Croatia, Bosnia and Herzegovina, Serbia, Bulgaria and Romania. Aristolochia clematitis, or European birthwort, is a common plant throughout the Balkans.
The study in Nature Communication focused on the most common form of kidney cancer, clear-cell renal cell carcinoma, which accounts for 2.4% of all adult cancers and more than 140,000 deaths annually.Though that may seem small compared to prostate and breast cancers, incidence rates have been increasing sharply, with the highest rates occurring in Central Europe.
The researchers performed whole-genome sequencing on DNA isolated from blood and tumor tissue samples and RNA sequencing on tumor and matched normal tissue samples taken from a total of 94 kidney-cancer patients in four countries: the Czech Republic, Romania, Russia and the United Kingdom.
“The most striking observation was the high frequency of a specific type of mutation pattern found in the Romanian patients,” says Yasser Riazalhosseini, an assistant professor of genetics at McGill University, who was on the team. “The specific sequence context surrounding these mutations and their predominance on the non-transcribed strand of DNA enabled us to hypothesize that the mutation is due to exposure to aristolochic acid during the patient’s lifetime.”
This same mutation pattern is found in patients suffering from urinary-tract cancer associated with Balkan endemic nephropathy. That disease is thought by many scientists to be due to consumption of wheat flour contaminated with seeds of Aristolochia clematitis. Aristolochic acid is also used in herbal remedies in parts of Asia.
“While the study included only 14 patients from Romania, the specific mutation pattern was found in 12 of them. As a result, we will analyze samples from more patients from Romania and elsewhere in the Balkan region, in follow-up research that is now underway to assess the extent of exposure,” says Professor Mark Lathrop, scientific director of the McGill University and Genome Quebec Innovation Centre, who led the study.
The broader results reported today also confirm that a certain signalling pathway, called PI3K/mTOR, is significantly deregulated in kidney cancer. The study further reveals that a connected pathway, called focal adhesion, is affected by molecular aberrations in many patients.
“This finding adds to evidence that targeted therapies for PI3K/mTOR signaling may be applied effectively to kidney cancer, and may help patients affected by abnormalities of the focal adhesion pathway, as well,” Riazalhosseini says.
