Most childhood cancers are isolated events, that is, they come “out of the blue” and there is no reason to expect that they might occur. This kind of diagnosis is called “sporadic”. Sporadic cancers have no family genetic causes or connections.
Many cases of PPB are not sporadic. In these cases, PPB signals a genetic predisposition to a set of cancers and cancer-like conditions in the PPB patient or in their young relatives. Current data collected by the PPB/DICER1 Registry indicates that in approximately 40% of PPB cases, the patient or family members are prone to other medical problems as described below. The family members can be siblings, parents, grandparents, uncles, aunts, cousins, etc. This set of conditions affecting PPB patients and their family is called the PPB Family Tumor and Dysplasia Syndrome. The problems generally affect young family members, in the first 20-25 years of their life. Although more must be learned about this syndrome, PPB has not been connected to problems later in life.
As it is currently understood, the PPB Family Tumor and Dysplasia Syndrome includes PPB (sometimes more than one case in a family), benign lung cysts (which have certain features of PPB but appear not to be malignant), cystic nephroma, other childhood cancers (especially sarcomas), childhood soft tissue dysplasias (such as nasal chondromesenchymal hamartoma and hamartomatous ‘juvenile’ intestinal polyps), ovarian Sertoli-Leydig cell tumors, ovarian dysgerminoma, testicular seminoma, and possibly nodular thyroid hyperplasias or thyroid cancers. Also in PPB families are occasional cases of childhood leukemia, brain tumors, gonadal germ-cell tumors and other illnesses; data on whether they are genetically related to PPB is insufficient to draw conclusions. It must also be emphasized that not every manifestation of this familial syndrome has yet been recognized. (See: Registry Publications Priest 2009; Priest 1996).
The PPB/DICER1 Registry is actively researching the genetic basis for this familial cancer syndrome. In April 2009, the PPB/DICER1 Registry and collaborators at Washington University St. Louis reported DNA mutations in a gene called DICER1 in 11 families with PPB, lung cysts, cystic nephroma and/or rhabdomyosarcoma. This research has subsequently been published (see Registry Publications: Hill Science 2009). This mutation, affecting all cells in the body, may be associated with PPB and associated conditions in familial PPB. Much more research must be done. It is especially important to learn how many PPB cases, including individual, non-familial, "sporadic" cases, are associated with this mutation The Registry requests all parents with children who have PPB to consider helping with this research (see below).
Whether to screen family members for PPB, lung cysts or other conditions associated with PPB is a difficult topic. If screening were done, one must decide what parts of the body to screen, how often to screen, at what age to start and to stop screening, and what types of medical tests to use. Screening temporarily provides reassurance, but after a few months, the sense of reassurance will fade. Continued screening for continued reassurance can cause long-term anxiety for parents and children. Repeated x-ray screening may be potentially harmful. The Registry recommends careful discussions between families and their physicians and perhaps genetic counselors to address these issues. Families and physicians are welcome to contact the Registry for further discussion of the pros and cons of screening.
Genetic Study in PPB: Extending Research into the Genetic Causes of PPB
The results of Registry research into genetic causes of PPB are summarized above. The Registry continues this important research in its major study looking at the genetic inheritance in PPB patients and their families. We ask that all PPB patients and their families consider participating. Visit http://www.ppbgeneticstudy.org/ or ppb.cancer.gov for more information.