Cancer and Your Genes

Other Cancers Seen in Families with RAD51D Mutations

Two days ago, we discussed a recent study by Dr. Nazneen Rahman and colleagues which clearly demonstrated that inherited mutations in a gene called RAD51D result in a substantial elevation in risk for ovarian cancer.  Some families with mutations in the study also had some other cancer types in the family tree.  So, does this mean that the other cancer types in these families are also due to the RAD51D mutations?

In short, the answer is that we don't know.  Ovarian cancer risk was the only one that Dr. Rahman and her colleagues could pin down as being associated with RAD51D mutations with any statistical confidence.  For the others, future studies can address the specific question; however, they may be challenging and require extremely large sample sizes in order to have the statistical power to answer the question.

Here are the other cancer types that were seen in the eight families with inactivating RAD51D mutations in the study:

Breast Cancer

•  Seen in 8 out of 8 families (not surprising given that the families were included in the study because they had both ovarian and breast cancer)
• There were 13 breast cancer cases total in these 8 families
• Two of the breast cancer cases were bilateral
• Seven of the 13 cases were found to have inactivating RAD51D mutations (the other 6 were not tested)
• In contrast to ovarian cancer, the association of RAD51D mutations with breast cancer was not statistically significant (Relative Risk = 1.32 with 95% confidence intervals from 0.59 - 2.96)

Colorectal Cancer

•  Seen in 5 out of 8 families (keep in mind that some of these extended families are quite large and that colorectal cancer is common)
• There were 8 total colorectal cancer cases in the 5 families
• None of the affected individuals were tested for the presence of mutations in this study

Lung Cancer

•  Seen in 1 individual in 1 out of 8 families (keep in mind that some of these extended families are quite large and that lung cancer is common)
• The individual with lung cancer was not tested for the presence of the familial RAD51D mutation in this study

Non-Hodgkin Lymphoma

•  Seen in 1 individual in 1 out of 8 families
• The individual with NHL was not tested for the presence of the familial RAD51D mutation

Pancreatic Cancer

•  Seen in 2 individuals total from 2 out of 8 families
• The 2 individuals with pancreatic cancer were not tested for the familial RAD51D mutation

Prostate Cancer

• A total of 2 cases were seen in 1 out of the 8 families
• The 2 individuals with prostate cancer were not tested for the familial RAD51D mutation

It's very important to keep in mind that seeing these cancers in these families could just be due to chance or to the fact that the families were more likely to come to the researchers' attention because of the other cancers (particularly breast cancer).  Thus, we can't say anything about whether RAD51D mutations may lead to elevated risk for any cancer other than ovarian cancer based on this study.  Nevertheless, it will be important in the future to keep an eye on this. 

Bottom Line Implications

1. Mutations in the RAD51D gene lead to ovarian cancer risk in some families in which the familial ovarian cancer risk is not explained by mutations in BRCA1/2

2. Although several other cancer types (including breast cancer) were seen in the families with mutations, there was no statistically significant evidence from this study implicating RAD51D mutations in risk for any of the other cancer types. 

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Selected References

Loveday C, Turnbull C, Ramsay E, et al.  Germline mutations in RAD51D confer susceptibility to ovarian cancer.  Nature Genetics 2011 (Published online August 7 2011)

Family History of Cancer Changes Over Time: Why You Need to Keep Your Primary Care Doctor Updated

If you are interested in cancer prevention, you may know that for common cancers family history is one of the most important and useful tools that we have to identify people at elevated risk (who are likely to benefit most from more intensive screening and/or preventative measures).

Despite this fact, discussion of family history often gets lost in the shuffle in primary care - which is not surprising given how much stuff today's healthcare providers need to pack into a visit that often may only last 10 minutes or so.   That said, many healthcare providers are doing a better job of asking about a family history of cancer, but it is usually a static, one-time assessment that may happen most at the time of initiation of primary care with a new doctor.

A newly published research article by Argyrios Ziogas, Nora Horick, Sharon Plon, Dianne Finkelstein and colleagues from the Cancer Genetics Network (CGN) in JAMA provides evidence and analysis that suggests that doctors and patients should also pay more attention to changes in family history of cancer over time.

Ziogas and colleagues used a couple of different analytical approaches to try to find answers to this question:

How often do family cancer histories change enough over time that they would merit changes in the intensity of screening based on American Cancer Society guidelines?

They focused on 3 of the most common cancer types: breast cancer, colorectal cancer, and prostate cancer.  Although there are a few caveats, in general, their results suggest that it is well worth it for people to make sure that their doctors are aware of any changes in their cancer history.

In the case of breast cancer, their results suggest that about 4 percent of women will have a change in their family history of cancer between the ages of 30 and 50 sufficient to suggest that they are in a somewhat higher risk group that may benefit from breast MRI screening (per American Cancer Society Guidelines). 

For colorectal cancer, their results suggest that about 5 percent of people will have a change in their family history of cancer between ages 30 and 50 that suggests that a more aggressive colonoscopy screening strategy may be warranted (per American Cancer Society Guidelines).

The impact of prostate cancer family history changes was less impressive. 

Overall, it seems clear that in the clinic we need to think of cancer family history as the often changing entity that it is, rather than the static, never changing, thing that may get entered in the clinic chart at the first visit and then never re-visited.

 What You Can Do: If someone in your family is newly diagnosed with cancer (parents, brothers, sisters, children, aunts, uncles, grandparents, cousins), let your physicians and other healthcare providers know about it the next time you see them.  This way, they can update the family history that they have on file for you and consider whether the information might suggest that you should have more intensive cancer screening.

Cited Reference

Ziogas A, Horick NK, Kinney AY, et al.  Clinically relevant changes in family history of cancer over time.  JAMA 2011; 306:172-8. 

Further Reading

Acheson LS.  Recording, interpreting, and updating the family history of cancer: implications for cancer prevention.  JAMA 2011; 306:208-10.

Qureshi N, Wilson B, Santaguida P, et al.  Collection and use of cancer family history in primary care: Evidence Report/Technology Assessment No. 159.  Rockville, MD: Agency for Healthcare Research and Quality, 2007.  AHRQ Publication 08-E001.

Scheuner MT, McNeel TS, Freedman AN.  Population prevalence of familial cancer and common hereditary cancer syndromes: the 2005 California Health Interview Survey.  Genet Med 2010; 12:726-35.

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Know someone with Hereditary Breast and Ovarian Cancer risk due to a BRCA1 or BRCA2 mutation?  Encourage them to check out BRCAscoop.com - a new high quality health information resource focused on newly published evidence related to cancer prevention, screening and treatment for people with BRCA1 or BRCA2 mutations

New Financial Assistance Program for Young Women with BRCA1 and BRCA2 Mutations Needing Help Paying for Screening Breast MRI

In a previous post we mentioned a Christina Applegate appearance on Oprah to discuss both learning that she (Ms. Applegate) had Hereditary Breast and Ovarian Cancer risk due to a BRCA1 mutation and the aftermath.  Since then, The Christina Applegate Foundation has worked to promote awareness of the importance of breast MRI screening for high-risk women.  However, one key impediment for some women is the cost of MRI.  Now, Right Action for Women is doing something to address this problem. 

Right Action for Women and Patient Services, Inc. recently partnered to deliver a new financial assistance program aimed at young women at high-risk for breast cancer needing assistance with the cost of screening breast MRI (link is to more info at BRCAscoop.com).

More on the Woman Who Filed an EEOC Complaint Claiming She Was Fired Over a Genetic Test Revealing a BRCA2 Mutation

The internet is abuzz with all kinds of information related to the case that we discussed yesterday here inovolving a Connecticut woman, Pamela Fink, who has filed a complaint with the EEOC and others alleging genetic discrimination under GINA (Genetic Information Nondiscrimination Act) .  She states that her former employer, MXenergy, fired her because of a genetic test that revealed that she carried a mutation in the BRCA2 gene, which confers very high lifetime risks of breast and ovarian cancer. 

Video is beginning to emerge (thanks to Nature News for pointing us in this direction) with more information about the case. 

Here is a piece from Fox61 News via courant.com:

 

 

 

Additionally, in another Fox news piece (posted along with the one above over at Nature News), Ms. Fink and her lawyer discuss the case.  She mentions that two of her sisters are cancer survivors.  This is not surprising in light of her decision to pursue prophylactic mastectomy, as women with close family members affected by breast cancer are more likely to pursue the preventative surgery in the context of a BRCA1 or BRCA2 mutation. 

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Know someone with Hereditary Breast and Ovarian Cancer risk due to a BRCA1 or BRCA2 mutation?  Encourage them to check out BRCAscoop.com - a new high quality health information resource focused on newly published evidence related to cancer prevention, screening and treatment for people with BRCA1 or BRCA2 mutations

Myriad Genetics Has Raised The Price for BRCA1 and BRCA2 Testing: North of $4,000 Now

The Yale Cancer Genetic Counseling blog notes that on April 1, Myriad reportedly raised the full price for full sequencing and rearrangement testing of the BRCA1 and BRCA2 genes to $4,040 (from $3,770).