Posts Tagged ‘european’

Prostate cancer screening reduces deaths by a fifth: Large, long-term European trial

Despite this new evidence for the effectiveness of prostate-specific antigen (PSA) testing to reduce mortality, doubts as to whether the benefits of screening outweigh the harms remain, and routine PSA screening programmes should not be introduced at this time, conclude the authors.

The European Randomised study of Screening for Prostate Cancer (ERSPC) began in 1993 to determine whether screening men for PSA reduces deaths from prostate cancer. It recruited men between the ages of 50 and 74 years from eight countries (Belgium, Finland, France, Italy, Netherlands, Spain, Sweden, and Switzerland) who were randomised to receive either PSA screening every 4 years (2 years in Sweden), or no intervention (control group). Men were referred for biopsy if their PSA concentration was higher than 3·0 ng/ml.

Results showed that screening appeared to reduce prostate cancer deaths by 15% at 9 years, and this improved to 22% at 11 years. Over 13 years follow-up, there was no further improvement in the relative reduction in prostate cancer deaths which decreased by roughly a fifth (21%) in the screening group compared with the control group, although men who were actually screened had a 27% lower chance of dying of prostate cancer.

However, the absolute benefit of screening steadily increased with longer follow-up. The number of men needed to be invited for screening to prevent one death from prostate cancer dropped dramatically from 1410 after 9 years of follow-up to 781 at 13 years. The number needed to be diagnosed and treated to prevent one prostate cancer death also fell from 48 to 27. The risk of advanced prostate cancer was also smaller in the screening group.

According to study leader Professor Fritz Schröder from Erasmus University Medical Center in the Netherlands, “PSA screening delivers a substantial reduction in prostate cancer deaths, similar or greater than that reported in screening for breast cancer. However, over-diagnosis occurs in roughly 40% of cases detected by screening resulting in a high risk of overtreatment and common side-effects such as incontinence and impotence.”

He adds, “The time for population-based screening has not arrived. Further research is urgently needed on ways to reduce over-diagnosis preferably by avoiding unnecessary biopsy procedures, and reducing the very large number of men who must be screened, biopsied, and treated to help only a few patients. One promising approach is multiparametric MRI technology which may be able to selectively diagnose aggressive prostate cancers and avoid the diagnosis of many inconsequential tumours that generally grow so slowly that most men will die of other causes. But for now, men must to be given well-balanced information including the screening harms of over-diagnosis and overtreatment.”

In a linked Comment, Ian Thompson at the University of Texas HSC, San Antonio, USA and Catherine Tangen at the Fred Hutchinson Cancer Research Center, Seattle, USA, discuss potential ways to mitigate the disadvantages of screening. They conclude, “The new findings from ERSPC are crucially important. In future publications from the study, the distribution of prostate cancer deaths by Gleason score and PSA at diagnosis will be important to understand how to tailor screening and treatment.”

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Gene increases risk of breast cancer to one in three by age 70

In a study run through the international PALB2 Interest Group a team of researchers from 17 centres in eight countries led by the University of Cambridge analysed data from 154 families without BRCA1 or BRCA2 mutations, which included 362 family members with PALB2 gene mutations. The effort was funded by the European Research Council, Cancer Research UK and multiple other international sources.

Women who carried rare mutations in PALB2 were found to have on average a 35% chance of developing breast cancer by the age of seventy. However, the risks were highly dependent on family history of breast cancer where carriers with more relatives affected by breast cancer, were at higher risk. Only a very small proportion of women worldwide carry such mutations and the researchers point out that additional studies are required to obtain precise estimates of mutation carrier frequency in the population.

PALB2 is known to interact with both the BRCA1 and BRCA2 and was first linked with breast cancer in 2007. As is the case for women who carry mutations in BRCA1 or BRCA2, women with PALB2 mutations who were born more recently tended to be at a higher risk of developing breast cancer than those born earlier. The reason why is unclear, but the researchers speculate that it may be related to factors such as later age at first childbirth, smaller families and better surveillance leading to earlier age of diagnosis.

Dr Marc Tischkowitz from the Department of Medical Genetics at the University of Cambridge, who led the study, says: “Since the BRCA1 and BRCA2 mutations were discovered in the mid-90s, no other genes of similar importance have been found and the consensus in the scientific community if more exist we would have found them by now. PALB2 is a potential candidate to be ‘BRCA3’. As mutations in this gene are uncommon, obtaining accurate risk figures is only possible through large international collaborations like this.

“Now that we have identified this gene, we are in a position to provide genetic counselling and advice. If a woman is found to carry this mutation, we would recommend additional surveillance, such as MRI breast screening.”

The researchers at Addenbrooke’s Hospital, part of Cambridge University NHS Hospitals Trust, have developed a clinical test for PALB2, which will become part of their NHS service. Clinical testing for PALB2 will be available also in certain other diagnostic laboratories worldwide.

There is evidence that cells carrying the PALB2 mutation are sensitive to a new class of drugs known as PARP inhibitors that are currently being trialled in BRCA1/2-related breast cancers. It is possible that these drugs would also work in PALB2-related breast cancer.

Dr Antonis Antoniou from the Centre for Cancer Genetic Epidemiology at the University of Cambridge adds: “Knowing the key genes that significantly increase cancer risk and having precise cancer risk estimates ultimately could help assess the breast cancer risk for each woman and allow better targeting or surveillance.”

Professor Peter Johnson, Cancer Research UK’s chief clinician, said: “We’re learning all the time about the different factors that may influence a woman’s chances of developing breast cancer. This particular mutation doesn’t make people certain to develop cancer, but it’s another piece of information to help women make proper informed choices about how they may help to minimise their own risk.”

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Eating resistant starch may help reduce red meat-related colorectal cancer risk

“Red meat and resistant starch have opposite effects on the colorectal cancer-promoting miRNAs, the miR-17-92 cluster,” said Karen J. Humphreys, PhD, a research associate at the Flinders Center for Innovation in Cancer at Flinders University in Adelaide, Australia. “This finding supports consumption of resistant starch as a means of reducing the risk associated with a high red meat diet.”

“Total meat consumption in the USA, European Union, and the developed world has continued to increase from the 1960s, and in some cases has nearly doubled,” added Humphreys.

Unlike most starches, resistant starch escapes digestion in the stomach and small intestine, and passes through to the colon (large bowel) where it has similar properties to fiber, Humphreys explained. Resistant starch is readily fermented by gut microbes to produce beneficial molecules called short-chain fatty acids, such as butyrate, she added.

“Good examples of natural sources of resistant starch include bananas that are still slightly green, cooked and cooled potatoes [such as potato salad], whole grains, beans, chickpeas, and lentils. Scientists have also been working to modify grains such as maize so they contain higher levels of resistant starch,” said Humphreys.

After eating 300 g of lean red meat per day for four weeks, study participants had a 30 percent increase in the levels of certain genetic molecules called miR-17-92 in their rectal tissue, and an associated increase in cell proliferation. Consuming 40 g of butyrated resistant starch per day along with red meat for four weeks brought miR-17-92 levels down to baseline levels.

The study involved 23 healthy volunteers, 17 male and six female, ages 50 to 75. Participants either ate the red meat diet or the red meat plus butyrated resistant starch diet for four weeks, and after a four-week washout period switched to the other diet for another four weeks.

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