乌鸦传媒

At the annual meeting of the American Urological Association, a study found that patients with active surveillance-eligible prostate cancer with either a 19q13 germline risk allele or a family history of prostate, breast, or pancreatic cancer had an elevated risk of prostate cancer-specific death.

In this exclusive 乌鸦传媒 video, , of Harvard Medical School and co-director of the Prostate Cancer Genetics Program of Massachusetts General Hospital in Boston, discusses .

Following is a transcript of his remarks:

This is a study that we did to investigate the role of family history of not just prostate cancer, but other genetically related cancers like breast cancer, ovarian cancer, pancreatic cancer, as well as germline risk variants that had been previously found through genome-wide association studies, on the prognosis of patients who would be active surveillance eligible.

So we examined patients in the health professionals follow-up study, which is a large prospective cohort study run by the Harvard School of Public Health. These are over 51,000 male health professionals that were recruited since the 1980s and followed for 30-plus years. And we identified just over 1,300 men who had been diagnosed with what would be considered active surveillance-eligible prostate cancer. So patients who had a diagnosis of NCCN [National Comprehensive Cancer Network] low risk or favorable intermediate risk prostate cancer, and had been followed for 30-plus years, and we were looking at outcomes of prostate cancer recurrence or prostate cancer-specific death.

And what we wanted to look at was what the impact of both family history and germline risk variants, kind of combined together, what their combined impact was, on these long-term outcomes of active surveillance-eligible prostate cancer.

And what we essentially found is that about a third of the patients in this cohort had some family history of either prostate cancer, breast cancer, or pancreatic cancer. And it turned out that this family history of not just prostate cancer, but also those genetically related other cancer types significantly increased the risk of both prostate cancer recurrence and prostate cancer-specific death over this long-term follow-up period.

Specifically, it was about a hazard ratio around 1.8. So about an 80% increased hazard of dying of prostate cancer if you had this family history and a first-degree relative.

We then looked at germline risk variant. So there's been a number of studies over the years that have developed polygenic risk scores for prostate cancer, which primarily have been developed in the context of studying cases versus control. So prostate cancer cases versus healthy controls to find risk variants associated with the development of prostate cancer.

And interestingly, when we looked at the prognostic impact of the polygenic risk store in this population, there was no association with prostate cancer-specific death or with recurrence. Which actually wasn't that surprising of a finding, because the polygenic risk scores have really been developed for presence or absence of prostate cancer, not necessarily distinguishing aggressive prostate cancer from indolent prostate cancer.

And so in this cohort, we found that the polygenic risk score was not predictive of prostate cancer long-term outcomes. But we then moved on to specifically focus on two loci in the genome that in previous studies have been associated with prostate cancer survival or aggressiveness.

And we found one locus on 19q13 that was associated in our cohort with both prostate cancer recurrence and prostate cancer-specific death. And then we moved to looking at a combined model, whether family history combined with this risk variant, if they were redundant with each other or whether they had independent additive value in predicting risk of these long-term outcomes.

And that was indeed the case. We found that in a model where you have each of these factors, each of these heritable risk factors, either the family history measure or this germline risk variant, the addition of each additional heritable risk factor increased the risk of prostate cancer-specific death significantly. Corresponding to roughly a hazard ratio of 1.7 for each of the two factors. So having both of the factors it was an additive risk that accumulated.

And this was held up in multivariable models, correcting for, or adjusting for, age, PSA [prostate-specific antigen] grade group stage, etc.

So again, this finding needs validation and additional cohorts, but we believe that there is an important role for germline genetic risk in counseling patients and how we select them for active surveillance. And we're definitely working on trying to identify additional cohorts to validate this finding.

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