Many of us are familiar with the BRCA1 and BRCA2 genes that, when mutated, are linked to an increased risk of breast cancer in women. But less often discussed is how BRCA gene mutations (and other, less-commonly known gene mutations) can affect men.
When a man carries a cancer susceptibility gene mutation, he has a higher risk of developing breast, prostate, and other cancers, as well as the same 50 percent chance of passing that mutation on to his children as women. Despite these facts, when people think of their family history of breast cancer, they tend to consider only their mother’s side of the family tree.
For this Men’s Health Week, we spoke with BCRF investigator Dr. Kenneth Offit, chief of the Clinical Genetics Service at the Memorial Sloan Kettering Cancer Center, to discuss inherited gene mutations and hereditary cancers in men. Watch the full video above or read on below.
At the Clinical Genetics Service at the Memorial Sloan Kettering Cancer Center, we see family members—men, women, and children—of patients that are at risk for hereditary cancers. Over the last 20 years, we’ve discovered a lot of the pathways that increase cancer risk in families, and so we’ve been providing genetic testing for patients with cancer and their family members for decades. We conduct the testing, give folks the results, and then advise as to what could be done for prevention, detection, and sometimes treatment. We also carry out research.
One of the things we’re always quick to point out is that all of us have BRCA genes. They’re very important. It’s only when you have mutations of these genes that they increase cancer risk. What these genes normally do is they help cells decide how to grow and regulate themselves. But if you happen to be born with a mutation in one of those genes, then the cells grow and divide in an abnormal way, and you go on and get a cancer as an adult or often as a child.
There are other genes whose names that are not as common, like PALB2, CHEK2, and ATM. These cause breast cancer in men and women, too. We also see hereditary cancers of other sites—the uterus and the ovaries—in women. In men and women, the colon, the thyroid, the stomach, and the pancreas are all sites of inherited cancers that are caused by mutations in normal growth regulatory genes.
For men, there is a risk of breast cancer, but it’s rare. Prostate cancer in men is probably the most significant cancer risk of having a BRCA gene mutation, more so than breast cancer.
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Yes, and all of genetics is ancestry. In the general population of men and women, around one in 400 people will carry a BRCA gene mutation. In certain populations in the world, that risk can be 10 times higher—one in 40.
My team and I discovered the most common mutation in the Ashkenazi/Eastern European Jews. These men had a higher risk of prostate cancers and aggressive prostate cancers. We also see a very high rate of these mutations in other groups that have been isolated geographically. Scandinavian countries are an example. We have these mutations in Iceland, Finland, and Norway, and some of them occur as commonly as they do in Ashkenazi Jews. Then we also have mutations that are common in other parts of the world that we sometimes see in the United States. For example, there’s a particularly common BRCA1 mutation in Poland. We then see it in Chicago, because of the city’s high population of individuals of Polish ancestry.
These mutations happen when populations are isolated. This could be because they’re literally on islands, like in the Scandinavian countries. Or, in the case of Eastern European Jews, the isolation was tied to persecution and a limiting of the area where they could live—an island defined by armies rather than by oceans.
One of the great misconceptions about the male connection with BRCA mutations is that one only looks to the mother’s side of the family—you’re only thinking of your mother’s history of cancer, your aunt’s, your sister’s. But, in fact, a BRCA gene mutation can come from either side. Fifty percent of the time it’s from your father, and 50 percent of the time it’s from your mother.
Some of the most challenging family histories that we see are those where a woman will come in and say, “I have no family history,” or a man will come in with a prostate cancer and a BRCA mutation and say, “I don’t have a family history.” Very often these mutations will come from the father, and they may just not have seen it.
To answer the first question about who should be tested, this is in flux right now. We’re at an inflection point where we don’t yet recommend that everybody just get screened. But I happen to believe, for example, that all men (and women) who are of Eastern European Jewish ancestry should be tested. That’s something that we’re in the process of proving is safe through our BCRF-supported study. Outside of one of those ancestries I mentioned that have a high risk, we have to just rely on family history pointing you in the direction of getting tested.
A man’s risk of getting breast cancer is exceedingly low—one in 1000, compared to one in eight for women. So, we don’t do routine breast cancer screening for men. But, for men who have a BRCA mutation, their chance of getting a breast cancer increases quite substantially to as much as one in 20. If you’re in that group where you have that lifetime risk, what can you do? We recommend these men start doing breast self-exams starting at age 35. I tell my patients to pat their chests in the shower in the morning. In men, it’s very easy to feel a little nodule.
And then, of course, we mentioned prostate cancer risk in men, and we have a blood test for that: the prostate-specific antigen (PSA). It’s controversial to some, but not, I think, in this setting. We recommend that for men with BRCA mutations, and, in fact, we even have a different threshold for what’s considered normal in a BRCA mutation carriers. From there, we do biopsies and find these prostate cancers at the early, curable stage.
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