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Increased cancer incidence, mortality linked to neurofibromatosis type 1
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Patients with neurofibromatosis type 1 appeared at an increased risk for cancer diagnosis and mortality, according to the results of a population study.
These data confirmed the substantial mortality burden associated with neurofibromatosis type 1 (NF1)-specific cancers, which include central nervous system and peripheral nervous tumors. However, results also revealed increased incidence of and/or mortality from breast cancer, pheochromocytoma, gastrointestinal stromal tumor, malignant fibrous histiocytoma and thyroid cancer in patients with NF1.
“NF1, an autosomal-dominant tumor predisposition syndrome with a birth rate as high as one in 2,000, is caused by mutations of the NF1 gene on chromosome 17,” Juha Peltonen, MD, PhD, of the department of cell biology and anatomy at University of Turku in Finland, and colleagues wrote. “Almost all adult patients with NF1 have cutaneous neurofibromas, which are benign tumors that do not become malignant. More than one half of patients with NF1 also have plexiform neurofibromas, which may become malignant.”
The most common malignancies associated with NF1 include intracranial gliomas and malignant peripheral nerve sheath tumors.
However, few epidemiologic studies have been performed to confirm the link between NF1 and increased cancer incidence.
Thus, Peltonen and colleagues conducted a representative, population-based study to determine the risk for cancer in patients with NF1, stratified by cancer type, age and sex.
The researchers linked a series of patients with NF1 (n = 1,404, representing 19,076 person-years) to data from incident cancers recorded in the Finnish Cancer Registry. They also had access to death information from 1987 to 2002, collected by the Population Register Center.
Researchers compared survival among patients with cancer with and without NF1 and calculated standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) for select cancers.
Overall, patients with NF1 had a greater cumulative risk for cancer by age 30 years (25.1% vs. 0.8%) and 50 years (38.8% vs. 3.9%) than the overall Finnish population.
Women with NF1 had a higher cumulative risk for cancer by age 50 than men (45.2% vs. 32%). The estimated lifetime risk for cancer was 59.6% among those with NF1 vs. 30.8% among the general population.
Peltonen and colleagues observed high incidence and mortality ratios among cancers traditionally associated with NF1, including malignant peripheral nerve sheath tumors (SIR = 2,056; 95% CI, 1,561-2,658; SMR = 2,301; 95% CI, 1,652-3,122) and CNS tumors (SIR = 37.5; 95% CI, 30.2-46; SMR = 30.2; 95% CI, 19.1-45.2). In total, malignant peripheral nerve sheath tumors and intracranial gliomas accounted for 63% of cancers in the cohort.
However, researchers also identified additional cancers associated with NF1. When excluding NF1-specific cancers — or nervous system and soft tissue malignancies — the SIR for cancer remained elevated among women (1.98) and men (1.96) with NF1.
Women aged younger than 40 years with NF1 had a breast cancer SIR of 11.1 (95% CI, 5.56-19.5) and SMR of 5.2 (95% CI, 2.38-9.88).
Additional NF1-related malignancies included gastrointestinal stromal tumor (SIR = 34.2), pheochromocytomas (SIR = 74.3), rhabdomyosarcomas (SR = 45.3), thyroid cancer (SIR = 2.71) and cancer of the pharynx and mouth (SIR = 3.21).
Notably high cancer incidences persisted among patients with NF1 aged younger than 15 years (women, SIR = 87.6; 95% CI, 58.6-125; men, SIR = 45.6; 95% CI, 28.4-68.5).
When excluding NF1-specific cancers, the SMR for cancer was 2.25 among all patients with NF1 (men, SMR = 2.01; women, SMR = 2.48). The researchers also observed increased mortality associated with breast cancer (SMR = 5.2) and thyroid cancer (SMR = 30.4).
Further, a smaller proportion of patients with cancer and NF1 — excluding those with nervous tissue cancers — achieved 5-year OS compared with patients with comparable cancers without NF1 (54% vs. 67.5%; P = .01).
“We speculate that the poor cancer survival rate in patients with NF1 may be related to cancer developing in the NF1 gene–deficient microenvironment; this background may be more permissive to cancer growth and invasion,” Peltonen and colleagues wrote. “The mutation of the NF1 gene per se may also alter the malignant cell population, leading to aggressive behavior of the malignancy. We conclude that NF1 germline and somatic mutations may contribute to human cancer in general, far beyond the NF1 syndrome itself.” – by Cameron Kelsall
Disclosure: Peltonen reports no relevant financial disclosures. Other researchers report research funding, honoraria and travel expenses from AbbVie, Boehringer Ingelheim, Fuji Pharma, GlaxoSmithKline, Mediplast, Pfizer, Roche, Steripolar and Takeda Pharmaceuticals.
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