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New prostate cancer genes found

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Researchers in Seattle and Sweden have identified five inherited genetic markers associated with aggressive, lethal prostate cancer.

The finding that could lead to the development of a simple blood test that could help determine who should receive aggressive treatment and who could opt for more conservative approaches.

“Biomarkers that could distinguish between patients with indolent versus more-aggressive tumours are urgently needed,” said Janet L. Stanford, Ph.D., co-director of the Fred Hutchinson Cancer Research Center Program.

“The panel of markers we”ve identified provides the first validated evidence that inherited genetic variants play a role in prostate cancer progression and mortality. Ultimately these markers could be used in the clinic, along with other known predictors that are used to assess tumor aggressiveness, such as a high Gleason score, to identify men with a high-risk profile,” she added.

For the study, the researchers analyzed DNA in blood samples taken from a population-based group of 1,309 Seattle-area prostate cancer patients who were age 35 to 74 at the time of diagnosis.

prostate cancer

Prostate cancer

A subsequent validation study of these 22 single-nucleotide polymorphisms, or SNPs (pronounced “snips”) was conducted in another population-based group of 2,875 prostate cancer patients in Sweden who were age 35 to 74 at diagnosis. Upon genotyping DNA from their blood, five of the 22 SNPs emerged as being significantly associated with death from prostate cancer.

The five SNPs were located in or tagged, one each, to five genes that may affect prostate cancer progression:

LEPR – The strongest marker associated with prostate cancer mortality in the study was the leptin receptor gene, which helps control tissue growth, inflammation, blood-vessel development and bone density. The latter effect makes LEPR an interesting candidate for understanding disease progression, since the primary metastatic site for prostate cancer is bone, and such metastases are predictive of fatal disease.

RNASEL – This gene is associated with hereditary prostate cancer and is associated with apoptosis (programmed cell death), inflammation and the ability of cells to proliferate and stick to each other (hallmarks of cancer growth).

IL4 – This Interleukin 4 gene is associated with tumor growth, blood vessel development and cancer cell migration.


CRY1 – Cytochrome 1 is a gene that impacts the circadian rhythm and thereby may affect androgen levels, which are known to be involved in prostate cancer progression.

ARVCF – This gene is a member of the catenin family of proteins, which help the inside and outside of cells “talk” to each other. Increased expression of ARVCF has been shown to disrupt cell adhesion, which may facilitate cancer progression.

Patients who carried four or all five of these genetic markers had a 50 percent higher risk of dying from their prostate cancer than patients who had two or fewer. The risk of dying from prostate cancer increased with the number of SNP genetic variants a patient carried.

“While previous studies have suggested that genetic background influences prostate cancer outcomes, this is the first study to validate genetic markers associated with lethal disease,” said Stanford.

The study has been published online ahead of the September issue of Cancer Epidemiology, Biomarkers and Prevention.

Paracetamol linked to blood cancers

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Regular users of paracetamol have an increased risk of developing blood cancers, researchers have found.

The tablets contain a chemical called acetaminophen which has been linked to cases of cancer in a number of individuals who were taking the drug.

The findings will terrify the millions in America and worldwide who pop the pills to cure minor ailments without so much as a second thought.

Earlier work has shown that aspirin use might lower the odds of dying from colon cancer but increase the risk of bleeding ulcers. The picture has been less clear for blood, or haematologic, cancers, however.

The finding adds another twist to the complicated evidence linking cancer and painkillers, and hints acetaminophen might be different from the rest.

‘Prior to this study there was very little evidence that aspirin reduces your risk of haematological cancers,’ said Emily White of the Fred Hutchinson Cancer Research Center in Seattle, who worked on the new research.

Paracetamol

Paracetamol

There were some suggestions that acetaminophen might increase the risk of the cancers, on the other hand, but those were based on individual cases of blood cancer.

Studies of individual patients aren’t considered as strong as the new one, which tracked a large population of healthy people over time.

‘We have the first prospective study,’ White said.

Still, she warned, there is no proof that acetaminophen causes cancer, and the new results need to be confirmed before they are used in any treatment decision.

Earlier work has linked acetaminophen to asthma and eczema as well, but scientists still don’t agree on whether the drug is the actual culprit or just an innocent bystander.

The new study suffers from the same limitations, in that people who use lots of painkillers could be dealing with medical problems that set them up for cancer down the road.

The scientists followed nearly 65,000 older men and women in Washington State. At the outset, they asked the participants about their use of painkillers over the past ten years and made sure that no one had cancer (except skin cancer).

Over some six years on average, 577 people — or less than one percent — developed a cancer involving the blood cells. Examples of such cancers include lymphoma and myelodysplastic syndrome, or MDS.


More than nine per cent of people who developed one of these cancers used high amounts of acetaminophen, compared to only five percent of those who didn’t get sick.

After accounting for things like age, arthritis and a family history of certain blood cancers, chronic acetaminophen users had nearly twice the risk of developing the disease.

‘A person who is age 50 or older has about a one-percent risk in ten years of getting one of these cancers,” White said. “Our study suggests that if you use acetaminophen at least four times a week for at least four years, that would increase the risk to about two percent.’

No other painkillers — including aspirin and ibuprofen — were tied to the risk of blood cancers.

Dr. Raymond DuBois, a cancer prevention expert at the University of Texas MD Anderson Cancer Center in Houston, said acetaminophen works very differently than other painkillers and so might be expected to have different effects on cancer.

‘It was quite surprising to see that acetaminophen use increased the risk of blood cancers,’ said DuBois, who was not involved in the study.

McNeil Consumer Healthcare, the Johnson & Johnson subsidiary that sells Tylenol, did not respond to requests for comment.

White said it is too soon to make any recommendations based on the new study, and that none of the painkillers is free of side effects.

‘Long-term use of any over-the-counter drug might have adverse effects,” she said. ‘You have to weigh the benefits against the risk of all the drugs.’