生物谷报道：冰岛研究人员最近发现，BRCA2变异基因会大大缩短前列腺癌患者的存活期。
据英国《新科学家》(NewScientist) 杂志网络版１３日报道，冰岛癌症登记处的研究人员发现，携带BRCA2变异基因的前列腺癌患者存活期大大低于那些携带这种基因正常版本的患者。
自１９９５年开始，研究人员一直在研究这种基因对乳腺癌的影响。携带BRCA2变异基因的女性患乳腺癌的危险会提高７倍。近年来，研究人员又开始研究BRCA2变异基因如何影响男性健康。
研究人员对５２７个病人的前列腺癌组织切片的脱氧核糖核酸（ＤＮＡ）进行了分析，发现其中３０个病人携带了BRCA2变异基因。研究显示，携带这种变异基因的男性在被诊断患前列腺癌后平均存活２年零１个月，比那些携带正常基因的病人少活约１０年，后者平均存活期为１２年零５个月。
这项研究的负责人拉菲·特里格瓦多迪尔建议，如果家庭成员中有人患与BRCA2变异基因有关的乳腺癌，那么这个家庭中的男性应从４５岁开始接受前列腺检查，而不是通常建议的５０岁。
原始出处:
Gene mutation slashes prostate cancer survival time
11:53 13 June 2007
NewScientist.com news service
Roxanne Khamsi
A gene mutation can radically alter the chances of survival for men with prostate cancer, new research has found.
Men who carry a mutated form of the BRCA2 gene seem to succumb to this type of cancer a decade earlier than those with a most common version of the gene.
Experts say that screening for the BRCA2 gene mutation – which is better known for raising the risk of breast cancer – could improve the outcome of prostate tumour treatment.
Our knowledge of BRCA2 dates back to 1995, when researchers first identified this gene and began to understand its effect on breast cancer. Women with mutations in either BRCA2 or the related BRCA1 gene face up to a seven-fold increase in the risk of breast cancer.
In recent years, scientists have started to piece together how BRCA2 mutations also influence men's health.
Doubled risk
Studies have found that men who carry certain variants of BRCA2 face a doubled risk of prostate cancer, and are six times more likely to develop pancreatic cancers than people with a normal version of the gene.
Laufey Tryggvadottir at the Icelandic Cancer Registry in Reykjavik and her colleagues decided to see if the BRCA2 mutation had any impact on the progression of prostate cancer once it developed.
According to the Prostate Cancer Foundation, prostate cancer strikes one in six men in the US. And Tryggvadottir says that when doctors conduct autopsies of elderly men who have died from a wide range of causes, including traffic accidents, they find cancerous prostate cells in two-thirds of these men.
But she stresses that only a fraction of men die as a result of prostate tumours: "The big challenge today is how to distinguish between a lethal cancer and a harmless one."
Howard Soule of the Prostate Cancer Foundation in Santa Monica, California echoes this view: "It would be helpful to know whose prostate cancer is aggressive and whose cancer is non-lethal."
Radically shorter
To help address this challenge, Tryggvadottir and colleagues retrieved prostate cancer biopsies that had been taken from 527 patients and deposited in their registry over the past few decades.
Researchers analysed the DNA in these samples and found that 30 of the men tested positive for a BRCA2 mutation, known as 999del5. Men with this mutation had an average survival time of 2.1 years following their cancer diagnosis – a decade shorter than patients with the normal gene, who lived 12.4 years on average.
"That's radically different," says Soule, who adds that patients would likely want to know which of these dramatically different prognoses applies to them.
Moreover, the new study revealed that carriers of the inherited gene mutation received their cancer diagnosis at an average age of 69 – five years earlier than those free of the mutation.
This indicates that the cancer developed earlier, so Tryggvadottir suggests that men with a history of BRCA2-related breast cancer in their family begin prostate screening at age 45, a few years before the generally recommended age of 50.
Watchful waiting
She adds that having a faulty version of the BRCA2 gene makes cancer more likely because the gene encodes for a protein involved in DNA repair.
Typically, if a man has high levels of prostate-specific antigen (PSA), doctors will conduct a biopsy of the organ. If the cells' DNA looks relatively normal, physicians recommend a period of "watchful waiting", because removal of the prostate can lead to unwanted side effects, including impotence and urinary incontinence.
Soule says that the new findings represent a step towards that goal of having "a test to know who should have their prostate removed today and receive aggressive therapy, and who should have watchful waiting". Immediate surgery and chemotherapy can prevent the tumour from spreading through the body.
Researchers estimate that 0.5% of men in Iceland carry the 999del5 BRCA2 mutation, and that a similar proportion of men through the world carry this or other BRCA2 mutations.
While the overall percentage of men who have the mutation is small, Tryggvadottir says these men likely represent a large number of those with lethal prostate cancer. Each year 28,000 men die of prostate cancer in the US alone, according to Soule.
Journal reference: Journal of the National Cancer Institute (DOI: 10.1093/jnci/djm005)
