Having a Close Relative With Blood Cancer Boosts One's Own Risk

A study published today by the journal Blood finds that those with a close relative with blood cancers are more likely to develop the disease themselves. This the first evidence published that familial risk, seen in many solid tumor cancers, exists in the hematological spectrum as well, according to the study.

Having a parent, sibling, or child with a blood cancer—and the number of first-degree relatives who get cancer—as well as the age of diagnosis all determine a person’s relative risk of developing various blood cancers, say the authors, led by Amid Sud, MD, PhD, of the Institute for Cancer Research, London.

There has been increased interest in genetic testing for solid tumor cancers, notably for the BRCA1/2 gene mutations that can be carried by men and women and drive breast, prostate, or pancreatic cancer; this year’s National Comprehensive Cancer Network guideline updates featured numerous recommendations in these areas. Now, Sud tells The American Journal of Managed Care® in response to an email that genetic testing in the hematological cancers “is an emerging area of interest.” He offered specific examples:

• Certain germline mutations “confer a particular disease phenotype and prognosis,” he said. In patients with certain genetic mutations, transplant conditioning regimens can cause bone marrow failure.
• Identifying a germline genetic mutation consistent with a certain syndrome may point to other health problems or call for testing of relatives, as it would affect who might be the right choice for a bone marrow donor.

Other research has shown elevated risk of blood cancer among first-degree relatives, but the authors said this examination of more than 153,000 records from patients with hematological malignancies is the largest and most extensive population-level study thus far. The data was extracted from 16 million records in the Swedish Family-Cancer Database.

The authors found that cases with a familial link accounted for 4.1% of all blood cancer diagnoses. The highest relative risks were for the following:

• Mixed cellularity Hodgkin lymphoma; standardized incident ratio (SIR), 16.7
• Lymphoplasmacytic lymphoma; SIR, 15.8.
• Mantle cell lymphoma; SIR, 13.3.

In addition, chronic lymphocytic leukemia (CLL) was linked to having with an elevated familial risk of other B-cell tumors and myeloproliferative neoplasms.

Still, the links for first-degree relatives for hematological cancers was not as strong as it is for some solid tumors—the breast, colorectum, and prostate—in which familial-linked cancers account for 8% to 15% of all cancers.

Right now, there are no screening initiatives for blood cancers, although a 2016 update to the World Health Organization classification for myeloid neoplasms and acute leukemia recognized the need to better understand familial risk, and Sud said in his email to AJMC® that developing better screening protocols is an important area of research.

“We hope these robust data will be used to inform guidelines on genetic testing and screening,” Sud said. If a person has a first-degree relative diagnosed with a blood cancer at a young age, surveillance may be appropriate, he said.

When asked if genetic susceptibility had a role yet in informing use of chimeric antigen receptor (CAR) T-cell therapy, Sud said the role of familial links “is currently unknown,” although research by his group and others have shown the importance of using genetic testing to direct the right targeted cancer drugs to the right patients.

He said there are many areas of research that can build on these results, pointing to current work in multiple myeloma, Hodgkin lymphoma, and CLL.

Reference

Sud A, Thomsen H, Sundquist J, et al. Analysis of 153,115 patients with hematological malignancies refines the spectrum of familial risk [published August 8, 2019]. Blood. doi: 10.1182/blood.2019001362.