We Are Family: Understanding Your Family History of Cancer

by Katy Henke

Family members share many things that can impact cancer risk: lifestyle choices, habits, physical environments and their genetic makeup. Of all of these, genetics can be particularly key.

Because of this, it’s important to understand your family history of cancer and how it may impact your risk for the disease. Some types of family history and related genetic mutations can greatly increase the risk of certain cancers, while other types can have an impact similar to common lifestyle risk factors - like being overweight.

So, take the opportunity over the holidays to talk with your family members about their health history. Jennifer Ivanovich, MS, MBA, CGC, a board certified clinical cancer genetic counselor at Siteman Cancer Center and Assistant Professor of Surgery in the Division of Public Health Sciences at Washington University School of Medicine, recommends asking some of the following questions:

• Has anyone in the family had cancer?

• If so, where did the cancer start or what was the specific cancer type?

• About what age was the person diagnosed? 

• Has the family member had genetic testing and, if so, what were the specific results? (Having a copy of the genetic testing results is always helpful).

There are many tools available to help chart your family health history. A doctor or genetic counselor is the the best source for understanding your family history of the disease and how it may affect your risk.

If your family history or genetics puts you at increased risk, your doctor may recommend special steps that can help you reduce or manage that risk.

A healthy lifestyle also remains important for people with a family history of cancer. While you cannot change your genes, shifting to healthier behaviors, such as quitting smoking and keeping weight in check, can improve your overall health and lower the risk of cancer and other important diseases.

Knowing that cancer runs in your family offers a great opportunity to focus on prevention. For tips on lowering cancer risk, check out  8IGHT WAYS to Stay Healthy and Prevent Cancer. Start with one or two changes, and build from there.

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To learn your risk for common diseases, visit Your Disease Risk calculator.

For more resources on family history, visit the CDC’s Family Health History website or the Surgeon General’s My Family Health Portrait website.

Photo: Pen to Paper by Dwayne Bent (CC License, CC BY-SA 2.0)

Practical Steps to Prevent Breast Cancer: Day 8 - Find Out Your Family History

It's day eight in our nine day series highlighting key steps and practical tips that can help women lower their risk of breast cancer. Previous days.

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Day 8 - Find Out Your Family History

Women with a strong family history of breast cancer can take special steps to protect themselves, so it’s important for women to know their family history of breast and other cancers. You may be at high risk of breast cancer if you have a mother or sister who developed breast or ovarian cancer (especially at an early age) or if you have multiple family members (including males) who developed breast, ovarian and/or prostate cancer. A doctor or genetic counselor can help you understand your family history of the disease.  A doctor is also the best source of information on ways to lower or manage your breast cancer risk.

Tips and Tricks – Family History

Learn your family history. Most women will have a general idea of their family history of breast cancer, but it’s a good idea to spend a little time to get a more detailed idea of your cancer history, especially if it’s pretty clear that breast or other cancers run in your family.  A doctor or genetic counselor can help.

Keep things in perspective. Most women with a family history of breast cancer are not at high risk of the disease. In most instances, family history behaves on par with many other breast cancer risk factors. Of course, women with a very strong family history (multiple family members with cancer or inherited BRCA1 or BRCA2 mutations) have a very strong risk of breast cancer. But even these situations don’t guarantee a woman will develop the disease.

Next Steps – Family History

Looking for more in-depth information on family history? Here are some good sources:

US Surgeon General
http://goo.gl/VTT2yU

Centers for Disease Control and Prevention
http://goo.gl/c2iNuO

Photo: Family Walk by Thomas Leth-Olsen (CC License, CC BY 2.0)

Setting the Record Straight on Cancer Prevention: Lifestyle Trumps "Bad Luck"

While the paper by Tomasetti and Vogelstein is certainly intriguing and will help guide future research on targeting prevention and early detection efforts, it is still a preliminary finding and does not reverse the long-term conclusion that is supported by decades of well-designed research in people:  that cancer is largely preventable.

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It's been hard to avoid the headlines this past week touting the conclusions of a new study in the journal Science that cancer is a disease largely caused by "bad luck."  Some of these headlines have been sensationalized; some have been more measured.  Together, they've seemed nearly ubiquitous.  And in some ways that's been positive, demonstrating that cancer - and its causes and prevention - remain an important topic to both the public and the media.

Unfortunately, the conclusions of the paper - and the subsequent coverage they've received - seem to reach well beyond what the actually findings of the study support, and in doing so, have incorrectly called into question what decades of overwhelming evidence shows:  that over half of all cancers - and up to three quarters of some cancers - could be prevented by regular screening and healthy lifestyle choices.

The new study by Johns Hopkins researchers Cristian Tomasetti and Bert Vogelstein gathered data on the number of stem cell divisions that occur in various tissues in the body and compared these data to annual incidence rates of cancers in those tissues.  Stem cells divide to replace cells in tissue that die or are lost.  This maintains the tissue.  Some tissues need a lot of cell divisions for maintenance.  Others need less.  When cells divide, the DNA in cells also replicate and divide, opening up the chance for random mutations that could eventually lead to cancer.

The researchers found a strong correlation between tissues' number of stem cell divisions and cancer in those tissues, attributing 65% of cancers to these divisions, and the random DNA mutations that can occur with them.

While the study is well-designed and executed, it also has some key limitations that don't fully support its overarching conclusions.

First, the study was not done directly in humans.  It correlated data on cancer rates with tissue cell division data generated from cell analyses done in labs.  It is essentially a laboratory-based study, and lab studies in general are fantastic ways to generate hypotheses on cancer causes but bad ways to generate conclusive evidence on actual causes of cancer in humans.  The research world is littered with promising findings in petri dishes and mice that were never proved in actual people.

Second, many of the cancers included in the study are those already known to have few, if any, known lifestyle risk factors.  And while the study included two common preventable cancers, lung and colorectal, it also did not include two other major cancers with key lifestyle factors - breast and prostate cancer.  Together, lung, colorectal, breast, and prostate cancers account for approximately half of newly diagnosed cancers in the United States, a number much higher than the   other serious cancers included in the study.  The study itself even showed that colorectal cancers and lung cancers (in smokers) were less due to "bad luck" mutations than most others in the study. Other analyses based on long-term studies in humans have found that up to 75 percent of lung and colon cancers could be prevented, as well as at least half of breast cancers.

Finally, simply because there is a correlation between stem cell division and rates of cancer does not mean that random DNA mutations are the precipitating cause of cancer.  Multiple cell divisions could accelerate the cancer-causing effects of lifestyle factors. And many lifestyle factors  - from obesity to smoking - are thought to increase the risk of cancer by fostering cell division and DNA changes that begin the cascade to cancer.  So what is described as random "bad luck" may actually have its genesis in lifestyle choices.

While the paper by Tomasetti and Vogelstein is certainly intriguing and will help guide future research on targeting prevention and early detection efforts, it is still a preliminary finding and does not reverse the long-term conclusion that is supported by decades of well-designed research in people:  that cancer is largely preventable.  In our own 2012 paper that also appeared in a Science publication - Science Translational Medicine - we conclude that over half of the 572,000 deaths from cancer in the United States in 2011 were caused by key modifiable risk factors, such as smoking, obesity, and lack of physical activity.

Of course, "bad luck" plays a role in any cancer - any disease, for that matter.  We know people who smoke and drink and weigh more than they should who live until their 90s, and we know the healthiest people in the world who are struck down by disease early in life.  Healthy choices, though, can greatly increase our odds of living longer and healthier lives.  It's no guarantee, but it helps to stack the deck in our favor.

For more on the preventability of cancer, see our page: Preventing Cancer - Today

PALB2 Mutation: A "New" Gene That Greatly Increases Breast Cancer Risk

Photo: Flickr/Micahb37

by Sarah Cortez

There’s been a recent surge in women asking for genetic testing for breast cancer, due in large part to Angelina Jolie’s public decision last year to get a prophylactic mastectomy after discovering she had a mutation in the BRCA1 gene. These days, another breast cancer gene has been making headlines, a gene called PALB2.

Mutations in BRCA1, and its related gene, BRCA2, are the two most important known genetic links to breast cancer risk. Well, new findings on PALB2 have some describing it as the “third gene” to be linked with breast cancer.

Previous studies have found that mutations in PALB2 combined with mutations in the BRCA genes increased the risk of breast cancer. PALB2 is even short for Partner and Localizer of BRCA2. What we didn’t know was how much the risk of breast cancer increased with a PALB2 mutation alone – that is without a related BRCA mutation.

In August, the New England Journal of Medicine published a study that characterized patients with only a PALB2 mutation. To do this, researchers identified patients who did not have a BRCA1/2 mutation but who had a history of breast cancer in at least one family member. These patients were then tested for the PALB2 mutation.

So, what did they find?

The results showed that a PALB2 mutation by itself increased the risk of breast cancer 9.5 times compared to the general population. They also showed that, for those with a mutation in PALB2, the risk of developing breast cancer by age 70 was about 33%, as compared to a 12% lifetime risk in the general population. Furthermore, for those with a PALB2 mutation who also had two first-degree relatives (like your mom and your sister) with breast cancer, the risk of developing breast cancer by age 70 increased to more than 50%. For comparison, a BRCA1 mutation increases your risk of developing breast cancer, by age 70, to 55-65%. So BRCA mutations are still considered more risky.

So what does all this new information mean to you?

Just like with the BRCA genes, it would only be recommended that you get screened for PALB2 mutation if you have a strong history of breast or ovarian cancer in your family, such as:

• Breast cancer in more than one family member

• Breast cancer diagnosed before the age of 50

• Breast cancer diagnosed in both breasts (bilateral breast cancer)

• Male breast cancer

• Breast cancer plus ovarian or pancreatic cancer

• Ashkenazi Jewish ethnicity

Many women at low risk for gene mutations are needlessly tested every year, which can cause a great deal of unnecessary anxiety.

If a woman tests positive for a BRCA mutation, we offer increased cancer screening, risk-reducing medications, prophylactic mastectomy, or some combination of these. While it’s likely such approaches will also help protect women with a PALB2 mutation, there is currently no evidence that they have benefit. More research is needed.

Genetic mutations like BRCA1/2 and PALB2 are frightening because they increase the risk of breast cancer by such a great degree. But it’s important to also keep in mind that they are rare. Around one in 400 women in the United States have a BRCA mutation, which translates to 0.25 percent of American women. And even women who have such mutations are not guaranteed to develop the disease.

For the large majority of women, the most important things they can do to improve their health and lower the risk of breast cancer is to focus on living an overall healthy lifestyle that includes: being physically active for at least 30 minutes a day, keeping weight in check, and drinking alcohol only moderately, if at all.

References

Antonis C. Antoniou, Ph.D., Silvia Casadei, Ph.D., Tuomas Heikkinen, Ph.D., Daniel Barrowdale, B.Sc., Katri Pylkäs, Ph.D., et al. Breast-Cancer Risk in Families with Mutations in PALB2. N Engl J Med 2014; 371:497-506.

Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. Journal of Clinical Oncology 2007; 25(11):1329–1333.

Mother/Daughter Tanning and the Dual Nature of Family History

We've dedicated a number of posts over the past year on the policy and health pitfalls of indoor tanning - from the potential benefits of the "tanning tax" (post) to surprisingly high rates of tanning by some youth (post).  Now comes a fascinating, if not perfectly surprising, little analysis on the influence parents can have as indoor tanning enablers.

The small study - reported in the New York Times (story) and printed as a research letter in the Archives of Dermatology (letter - subscription required for full text) - included just over 200 female college students who had at any time in their lives tanned indoors.  Results showed that 40 percent of these students had had their very first tanning experience with their mothers, and that this mother/daughter group of students started tanning at earlier ages and were much more likely to be heavy tanners in college than those who'd first tanned with friends or gone on their own.

For an activity that has well demonstrated health risks, it's surprising that such a high percentage of students were actively introduced to tanning by a parent.  Using an extreme example, it's hard to imagine such a high percentage being introduced to smoking in the same way.

But perhaps the most interesting aspect of the study is how well it demonstrates the dual way that family history may influence future risk of disease.  Genes can certainly play a role but so to can the lifestyle choices that also permeate families - whether it's the food served in the kitchen or the activities done for leisure.  And with over half of all cancer and up to 75 percent of heart disease and diabetes preventable with things we can all do, it's important to realize that the choices made by families could have just as much, if not more, influence on health than the genes they carry.

Is obesity genetic?

While lifestyle contributes substantially more to risk of cancer (and other chronic diseases) than genetics alone, the interplay between genetics and lifestyle is a subject of increasing interest. That's what makes a new study out of the UK, published in PLoS Medicine so exciting.

The researchers took 12 genetic mutations that had previously been found to be associated with obesity risk and examined how they combined to be associated with risk of weight gain. The presence of each additional mutation increased risk of weight gain -- the more mutations, the greater the risk. The mutations significantly increased the risk of obesity by 16%. The researchers then did something quite novel, using the data the participants reported about how physically active (or not) they were, the researchers re-examined the associations. In the inactive men and women, the association was stronger than in the inactive people. What this means is that the effect of genes were stronger in the people who were inactive - or - that physical activity "erased" some of the genetic predisposition - about 40% of it.

What does this mean for those of us who have no idea how "genetically predisposed" we might be to obesity? Physical activity has benefits for everyone, but for individuals who are genetically predisposed to obesity, physical activity is especially important. It also means that a genetic predisposition to obesity isn't cause for "doom and gloom" - there ARE things you can do to counter it - notably, being physically active!