Family ties: Inherited genetic variants increase risk of Hodgkin lymphoma

Why did my child get cancer? Clinicians have longed for a way to help answer this question. Doctors knew Hodgkin lymphoma sometimes occurs in families, but why this happens has been a mystery. Scientists at St. Jude Children’s Research Hospital have now helped solve it. The researchers studied multiple families affected by Hodgkin lymphoma and identified genetic variants linked to an increased risk of developing the disease. The findings appeared as a first edition in Blood.

Hodgkin lymphoma is a cancer of the lymphatic system (part of the immune system) that affects lymph nodes but can spread to the spleen, liver, bone marrow and lungs. As many as 7,000 new cases of the disease are diagnosed in the United States each year. Hodgkin lymphoma is the most common type of cancer in adolescents and has a five-year survival rate of 90-95%.

“We’ve never been able to tell these families anything other than its just bad luck because nobody knew why more than one family member would develop Hodgkin lymphoma,” said co-first and co-corresponding author Jamie Flerlage, M.D., St. Jude Department of Oncology. “We took on this study because understanding what is causing cancer in these families will help us to better counsel people about their chances of passing on genetic risk to their offspring, as well as help us identify novel targets that might potentially be used to create new treatments.”

Family pedigrees help reveal variants

To study Hodgkin lymphoma occurrences in families, the researchers created pedigrees, a type of diagram that reveals familial connections while tracking the incidences of cancer. The selection criteria required two or more first-degree relatives with Hodgkin lymphoma, one of whom needed to be younger than 21 years of age when diagnosed.

Scientists performed whole genome sequencing on 234 members of 36 families and identified 44 variants (33 coding and 11 noncoding) that increase the risk of developing Hodgkin lymphoma. The findings included novel gene variants that had not been previously linked to predisposition to the disease such as PAX5, GATA3, IRF7, EEF2KMT and POLR1E as well as known variants such as KDR and KLHDC8B.

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