Family Members at Higher Risk for Blood Cancers

Pam Harrison

September 09, 2019

Individuals who have a first-degree relative (parent, sibling, or child) with blood cancer have a higher likelihood of being diagnosed with the disease, and this risk is higher for that of some solid tumors.

A new study, described by authors as the largest and most comprehensive to date, found a familial link in 4.1% of all blood cancer diagnoses.

This is higher than cancers of the central nervous system (1.8%), kidney cancer (2.8%), and pancreatic cancer (3%), but is lower than those of the breast (8.5%), colorectum (10.1%), and prostate (15.3%).

"We hope these robust data will be used to inform guidelines on genetic testing and screening. Certainly there are a number of individuals, such as those with a relative diagnosed at a young age and/or with more than one affected first-degree relatives, for whom counseling, genetic testing, and surveillance may be appropriate," lead author Amit Sud, MD, PhD, from the Institute of Cancer Research London, United Kingdom, commented in a statement.

"Speaking to a lot of clinicians across the country, a lot of them do report that patients have the same or a similar hematological malignancy [as another family member] but it's always been difficult to know whether this is by chance or not," Amit told Medscape Medical News.

"So it was a bit surprising that we found we have tumors thought to be derived from different lineages within the hematopoietic system, but actually our results suggest there are shared etiological factors underlying these tumors, and this information improves our understanding of the causes of, and potential inherited predisposition to, blood cancers," he added.

The study was published online August 8 in the journal Blood.

Sud and colleagues used the Swedish Family-Cancer Database to estimate familial relative risks of the major hematological malignancies in a total of over 16.1 million individuals.

"We considered all incident cases of hematological malignancies diagnosed between 1958 and 2015," the investigators explain.

Out of this large cohort, 153,115 patients had a primary hematological malignancy between the start and the end of the study.

"Almost all of the hematological malignancies showed statistically significant increased familial risks for the same tumor type," the authors note.

The team then quantified familial relative risks for each hematological malignancy by calculating standardized incident ratios in their 391,131 first-degree relatives.

The familial relative risks for first-degree relatives to develop the same malignancy were increased 1.5-fold for acute myeloid leukemia; 6.8-fold for essential thrombocythemia; 6.9-fold for myelodysplastic syndrome; and 7.7-fold for polycythemia vera.

For B-cell tumors there was a twofold increase in familial relative risk for diffuse large B-cell lymphoma, follicular lymphoma, and multiple myeloma.

Familial relative risk increased to 5.6-fold for chronic lymphocytic leukemia; 8.3-fold for hairy cell leukemia; 9.8-fold for nodular sclerosis Hodgkin lymphoma; 13.3-fold for mantle cell lymphoma, 15.8-fold for lymphoplasmacytic lymphoma/Waldenström macroglobulinemia; and 16.7-fold for mixed cellularity Hodgkin lymphoma.

The strongest familial relative risks tended to be disease-specific, the researchers note.

However, they also identified distinct patterns of familial risk — predominantly cell-lineage specific.

For example, chronic lymphocytic leukemia shared familial risk with nearly all of the B-cell tumors, the investigators observe.

Familial risks were also identified across cell lineage with Hodgkin lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, and multiple myeloma, all of which shared risk with a number of myeloid malignancies, the authors point out.

Lifetime Cumulative Risk

In the general Swedish population, the lifetime cumulative risk of all primary hematological malignancies, non-Hodgkin lymphoma, and chronic lymphocytic leukemia are 3.4%, 1.3%, and 0.4%, respectively.

These risks increased significantly for first-degree relatives of patients diagnosed with the same three types of malignancy at 4.3%, 2.2%, and 2.3%, respectively.

However, for patients with two or more first-degree relatives affected by all primary hematological malignancies, the elevated cumulative risk was 7.4%, the investigators report.

The same pattern of increased risk when two or more first-degree relatives were affected was seen across different hematological malignancies as well.

Table. Cumulative Risk Based on Number of First-Degree Relatives Affected

  General Population 1 Affected First-Degree Relative ≥2 Affected First-Degree Relatives
Non-Hodgkin lymphoma 1.3% 2.1% 2.4%
Chronic lymphocytic leukemia 0.4% 2.1% 8.6%
Myeloid malignancies 0.7% 1.4% 4.4%
Myeloproliferative neoplasm 0.3% 1.2% 3.2%

 

Sud and colleagues note that while the familial relative risks associated with some hematological malignancies are high relative to those associated with some solid tumors, the absolute lifetime risk of developing a hematological malignancy even among first-degree relatives is often extremely low.

"For example, given that the population lifetime risk of chronic lymphocytic leukemia is only 0.4%, the familial relative risk translates to 2.2% for a first-degree relative of a CLL case," the researchers note.

Implications for Screening

This low level of risk even in first-degree relatives has implications for screening, Sud suggested.

Firstly, as he explained, screening is only useful if there is a reliable test for a given disease.

Physicians also have to be able to offer an effective treatment if patients are diagnosed at an earlier stage of disease because the disease was detected upon screening.

A disease also needs to be reasonably common in the population for a screening program to be valuable, Sud noted.

"If we apply these principles to the hematological malignancies, a lot of them don't past these tests, particularly given how uncommon these malignancies are," he emphasized.

One exception to this rule might be for patients diagnosed with chronic lymphocytic leukemia.

"Monoclonal B-lymphocytosis (MBL), the precursor of CLL, is present in 3% to 4% of adults over 40 years of age and 14% to 18% of first-degree relatives of CLL," the authors explain.

This might render screening relevant in this particular group of patients, Sud suggested.

Knowing the lifetime cumulative risk of various hematological malignancies might also be useful for patients, he added.

"In the clinic, I've often encountered patients who have a first-degree relative with a hematological malignancy and their question is: 'What are the risks for me?' " Sud recounted.

"So it's useful to be able to refer to this study and say, this is what your lifetime risk for this particular malignancy is."

This study was supported by the German Cancer Aid, the Swedish Research Council, Region Skåne, and Bloodwise. The study authors have disclosed no relevant financial relationships.

Blood. Published online August 8, 2019. Abstract

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