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The 2008 NF Conference was held last weekend (June 6 — 10) in Bonita Springs, Florida. The preeminent annual meeting provides a forum for basic and clinical neurofibromatosis (NF) investigators to present their research (pronounced noor-oh-fahy-broh-muh-toh-sis). The conference was attended by over 200 researchers from around the world

This year’s theme — Genes to Complications to Treatments — highlighted the progress being made in NF research and clinical care, as well as the research programs of the Children’s Tumor Foundation. Last year’s NF Conference focused on models, mechanisms and therapeutic targets.

The neurofibromatoses are familial cancer syndromes that predispose individuals to the development of a variety of benign and malignant tumors in the central and peripheral nervious systems. The disorders cause tumors to grow along various types of nerves and can also affect the development of bones and skin. Neurofibromatosis has been classified into three distinct types:

• Neurofibromatosis type 1 (NF1) occurs in 1:3,500 births and is caused by a mutation of the NF1 gene on chromosome 17q11.2. NF1 diagnostic criteria (two or more) include cafe-au-lait macules, freckling, optic glioma, Lisch nodules, bony abnormalities, a first-degree relative with NF1, two or more benign nerve sheath tumors (neurofibromas) of any type, or at least one plexiform neurofibroma [1-2].
  At least 95% of NF1 patients develop benign tumors called neurofibromas [3], which may be disfiguring or associated with pain and neurological defect. As there is no cure for neurofibromatosis, the only therapy is surgical removal of the tumor and associated nerve. Approximately 6 — 13% of NF1 patients will progress and develop a malignant peripheral nerve sheath tumor (MPNST), an aggressive sarcoma that has a high mortality rate (~ 50%) [4].

• Neurofibromatosis type 2 (NF2) occurs in 1:25,000 births and is caused by a mutation of the NF2 gene on chromosome 22q12. Ninety percent of NF2 patients develop bilateral vestibular schwannomas and/or spinal schwannomas. Enlarging schwannomas can compress adjacent structures, resulting in deafness or other neurologic deficits depending on their location. Surgical removal of these tumors is difficult, often resulting in patient morbidity. Although 95% of schwannomas occur sporadically, multiple schwannomas are the hallmark of inherited NF2 [5].

• Schwannomatosis occurs in 1:40,000 patients and, in contrast to NF2, develop multiple peripheral schwannomas, but not schwannomas of the vestibular nerve. Schwannomas in schwannomatosis patients are often associated with severe, intractable neuropathic pain and sometimes numbness, tingling and weakness. It was believed that a germline mutation in an unidentified gene predisposes patients to NF2 mutation [6]. Recently, the INI1 gene was identified as a possible schwannomatosis gene [7-8].

Both NF1 and NF2 are tumor suppressor genes.

The Children’s Tumor Foundation (CTF) is dedicated to ending neurofibromatosis through research. The CTF has funded NF research for over 25 years with the goal of identifying NF drug therapies and improving the lives of those living with the disorder. The Foundation also endeavors to increase public awareness of NF and provides resources for NF patients and their families.

For more information on NF, visit the Children’s Tumor Foundation and Neurofibromatosis Cafe.

CTF medical podcasts are also available.

References

1. Riccardi VM. The prenatal diagnosis of NF-1 and NF-2. J Dermatol. 1992 Nov;19(11):885-91.
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2. Gutmann et al. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA. 1997 Jul 2;278(1):51-7.
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3. Rasmussen and Friedman. NF1 gene and neurofibromatosis 1. Am J Epidemiol. 2000 Jan 1;151(1):33-40.
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4. Evans et al. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet. 2002 May;39(5):311-4.
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5. Evans et al. A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity. J Med Genet. 1992 Dec;29(12):841-6.
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6. Jacoby et al. Molecular analysis of the NF2 tumor-suppressor gene in schwannomatosis. Am J Hum Genet. 1997 Dec;61(6):1293-302.
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7. Hulsebos et al. Germline mutation of INI1/SMARCB1 in familial schwannomatosis. Am J Hum Genet. 2007 Apr;80(4):805-10. Epub 2007 Feb 16.
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8. Hadfield et al. Molecular characterisation of SMARCB1 and NF2 in familial and sporadic schwannomatosis. J Med Genet. 2008 Jun;45(6):332-9. Epub 2008 Feb 19.
   View abstract

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Everyone knows that a good education is important for getting a good job. Now researchers are finding that being well-educated can lengthen your life. The study, published earlier this month in the journal PLoS ONE, finds that socioeconomic inequalities in the U.S. death rate between people with less than a high school education and college graduates increased from 1993 to 2001 [1]. The widening gap is due to (i) significant decreases in mortality from all causes, heart disease, cancer, stroke and other conditions, in the most educated and (ii) unchanged or increasing death rates in the least educated.

Epidemiologists at the American Cancer Society (ACS) worked with scientists from the Centers for Disease Control and Prevention’s National Center for Health Statistics (NCHS) to analyze over 3.5 million deaths from 1993 to 2001. They used data from the National Vital Statistics System (NVSS) and death certificate information to calculate annual age-standardized death rates for 25 — 64 year olds by level of education for all causes of death as well as for the seven most common causes of death (heart disease, cancer, stroke, HIV infection, diabetes, chronic lung disease, accidents).

The study restricted the analyses to deaths among non-Hispanic whites and blacks. It also excluded deaths that occurred in seven states (Georgia, Kentucky, New York, Oklahoma, Rhode Island, South Dakota and West Virginia) because completeness of education on death certificates in these states was less than 80% in at least one of years considered in the study.

The study found that between 1993 and 2001, the ratio of the all cause death rate in people with less than 12 years versus greater than or equal to 16 years of education significantly increased in white and black men, and in white women, indicating that those with a college education or better had an increased life expectancy. Contributing to the inequality was significant reductions in mortality for the most educated men (36% in black men and 25% in white men), largely due to decreases in death rates from HIV infection, cancer and heart disease.

Interestingly, the decrease in all cause death rates among men became larger with each additional increment of educational attainment (i.e. 12 years of education vs. 13 — 15 years vs. greater than or equal to 16 years). In women, this affect was only observed with greater than or equal to 16 years of education.

The study results support a previous investigation of county-level mortality published last month showing a steady increase in mortality inequality across the U.S. [2]. In that study, death rates between 1983 and 1999 increased for women in a large number of counties, principally due to chronic diseases related to smoking, overweight and diabetes, and high blood pressure. Most counties that showed a worsening of life expectancy were in the deep South, along the Mississippi River and in the Appalachia, extending into the southern portion of the Midwest and into Texas.

Between 1961 and 1983, counties with increased or decreased life expectancy improvements had relatively similar levels of income. However, after 1983, gain in life expectancy was positively associated with county income. Thus, those who were disadvantaged did not benefit from the increase in life expectancy experienced by the advantaged, demonstrating a large health inequality.

What does all this mean? It means those with less education are getting left behind and literally dying earlier as a result. ACS chief executive officer Dr. Otis W. Brawley, M.D. said that [3]:

People [in the U.S.] with less education have fewer financial resources, less access to health insurance or stable employment, and less health literacy. As a result, while the death rate among the most educated Americans is dropping dramatically, we’re seeing a real lack of progress or even worsening trends in the least educated persons. The gap between the best and worst off in the country is actually getting wider.

Last year, the American Cancer Society launched the Access to Health Care campaign, a national initiative to raise awareness about the problem of true access to health care. The website shows what is being done to help those uninsured and underinsured and how you can help.

Education is a marker of socioeconomic position. Lower educational attainment and thus a poorer socioeconomic position is associated with a variety of factors that affect health, including decreased financial resources, reduced access to health insurance and health literacy. Given that one of the CDC’s strategic imperatives is “all people, and especially those at greater risk of health disparities, will achieve their optimal lifespan with the best possible quality of health in every stage of life” [4], these results are troubling and highlight the growing problem with the U.S. healthcare system.

References

1. Jemal et al. Widening of socioeconomic inequalities in U.S. death rates, 1993-2001. PLoS ONE. 2008 May 14;3(5):e2181. DOI: 10.1371/journal.pone.0002181
   View abstract
2. Ezzati et al. The reversal of fortunes: trends in county mortality and cross-county mortality disparities in the United States. PLoS Med. 2008 Apr 22;5(4):e66.
   View abstract
3. Worsening Health Trends Among Least Educated. American Cancer Society News Center. 2008 May 14.
4. Center for Disease Control and Prevention’s Health Protection Goals. Accessed 2008 Jun 2.

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