Epidemiology of Glioma Quinn T. Ostrom, Ph.D., M.P.H.

Transcription

1 Epidemiology of Glioma Quinn T. Ostrom, Ph.D., M.P.H. Department of Population and Quantitative Health Sciences Case Comprehensive Cancer Center Case Western Reserve University

2 Estimated New US Cancer Cases 2017 Brain & other nervous system 1.6% Brain & other nervous system 1.2% ACS, /30/2017 2

3 Estimated US Cancer Deaths 2017 ACS, /30/2017 3

4 Overall incidence of primary brain and CNS tumors is 22.6 per 100,000 population Malignant: 7.2 per 100,000 population Non-Malignant: 15.5 per 100,000 population CBTRUS, /30/2017 4

5 Gliomas are the most common type of malignant brain tumor Gliomas account for ~27% of all brain tumors, and ~80% of malignant tumors Glioma is a heterogeneous disease with multiple subtypes The most common glioma histology glioblastoma (GBM) (~56%) Very poor outcomes Lower grade gliomas (LGG, or non-gbm) are the second most common type of glioma in adults (~30%) CBTRUS, /30/2017 5

6 Incidence of glioblastoma varies across the population Incidence of glioblastoma increases with age. Median age at diagnosis is 64. Incidence is higher in males as compared to females Globally: Incidence of glioma is highest in Northern Europe. United States: Incidence is highest in non-hispanic whites Higher socioeconomic status has been associated with increased risk of glioblastoma (Porter et al., 2015) Glioblastoma Incidence in the US by gender and age ( ) Glioblastoma Incidence in the US by race and ethnicity ( ) 11/30/2017 Thakkar et al.,

7 Survival Outcomes after diagnosis with glioblastoma are generally poor. Median survival: 12 months (Stupp et al., 2005) Five-year relative survival: ~5% (Thakkar et al., 2014; CBTRUS 2017) Several factors predict improved survival: High Karnofsky Performance Score (KPS) Younger age at diagnosis Greater extent of surgical resection Biomarkers (MGMT promoter methylation, mutation of IDH1) 11/30/2017 7

8 Incidence of glioblastoma has not changed substantially since the 1990s Glioblastoma Incidence in the US (Ages 18+, ) APC=-7.3% (95% CI: -11.1%, -3.3%) APC=2.7% (95% CI: 1.8%, 3.6%) APC=0.4% (95% CI: 0.1%, 0.7%) Incidence increases in the 1980s and 1990s are often attributed to increasing use of new imaging technologies. Since 1992, incidence of glioblastoma among adults has increased 0.4% per year in the US. These incidence patterns are similar to those observed in other countries. APC= Annual Percentage Change; 95% CI= 95% Confidence interval SEER, /30/2017 8

9 Searching for a cause for glioma Many environmental and genetic risk factors have been studied. No environmental risk factor accounting for a large number of glioma cases has been identified. Validated environmental risk factors likely account for only a fraction of incident cases No genetic risk factors that explain a large proportion of inherited risk for glioma have been identified Genetic factors are estimated to account for ~25% of glioma risk (Kinnersley et al., 2016) A small proportion of gliomas are due to inherited syndromes Genetic association studies have identified common genetic variants that explain ~27% of genetic risk for glioblastoma (Melin et al., 2017) 11/30/2017 9

10 GENETIC GLIOMA RISK FACTORS 11/30/

11 Inherited syndromes associated with glioma Estimated that hereditary cancer syndromes account for ~1% of adult glioma cases Neurofibromatosis 1 (NF1) Neurofibromatosis 2 (NF2) Tuberous sclerosis (TSC1, TCS2) Lynch syndrome (MSH2, MLH1, MSH6, PMS2) Li-Fraumei syndrome (TP53) Melanoma-neural system tumor syndrome (p16/cdkn2a) Ollier disease/maffucci syndrome (IDH1,IDH2) Image source: 11/30/

12 Genetic association studies in glioma families Familial glioma (2+ glioma cases within a family) accounts for ~5% of glioma cases Family-based studies have consistently demonstrated that first degree relatives of glioma patients have ~2x the glioma risk in comparison to the general population Linkage studies in affected glioma families have not identified high-penetrance risk variants that are able to be validated. Additional analyses of these families have found that most inherited mutations in glioma families are private. 11/30/

13 Genome-wide association studies have identified 12 common genetic variants associated with sporadic glioblastoma risk GBM only; ~5,000 cases and ~14,400 controls Melin et al., /30/

14 VALIDATED GLIOMA RISK FACTORS 11/30/

15 Ionizing radiation exposure ERR estimates for glioma by study Therapeutic radiation exposure to the head has consistently been associated with increased risk of brain tumor Israeli Tinea Capitus cohort (Sadetzki, et al 2005) Childhood cancer survivors cohorts (Neglia, et a. 2006) Glioma risk after therapeutic radiation exposure is inversely associated with age at exposure Mixed or minimal evidence Atomic bomb studies Diagnostic radiation (e.g. CT scans, x-rays) Brazanga et al., (2012) Odds ratio for glioma in relation to total dose and age at treatment Inskip et al., (2016) 11/30/

16 Allergies and atopic disease History of allergies and atopic conditions has consistently been associated with decreased risk of glioma. Respiratory allergies Asthma Eczema Effect is consistent for both glioblastoma and lower grade glioma All Allergies Glioblastoma This inverse association has been consistent across multiple studies 11/30/2017 Amirian et al., (2016) 16

17 UNPROVEN GLIOMA RISK FACTORS 11/30/

18 Cellular phones (non-ionizing radiation) Most studies have not observed increased odds of glioma for having ever been a regular cellular phone user. Small increases in odds have been observed in users with the highest total use INTERPHONE, 2010; Cardis et al., 2011 Cohort studies have shown null association between cellular phone use and glioma Benson et al., 2015; Frei et al., 2011 Time trends analyses from multiple countries have shown no significant increases in incidence that would be expected given estimated risk ratios from case-control studies de Vocht et al., 2011; Deltour et al., 2012; Little et al., 2012; Chapman et al., /30/2017 INTERPHONE Study Group (2010) 18

19 Electromagnetic fields Many studies have attempted to assess the association between occupational exposure to electromagnetic fields and risk of brain tumors EMF exposure can be difficult to accurately measure Many studies construct job exposure matrices (JEMs) based on job title and length of employment Results of previous case-control studies have been mixed. In the INTEROCC consortium, increased odds were observed only in individuals with most recent exposure (Turner, el al. 2014) Turner et al., (2014) 11/30/

20 Other explored sources of occupational exposures Mixed or minimal evidence Farming associated with increased risk of glioma (Ruder et al., 2009) Insecticides associated with increased risk of glioma (Louis et al., 2017) Pesticides associated with increased risk of glioma (Yiin et al., 2012) Military radiation exposure associated with increased risk of glioma, with increased effect in soldiers of higher rank (Grayson, 1996) Rubber processing (Straif et al., 2000) No evidence Metals and welding fumes (Parent et al., 2017) Solvents (Benke et al., 2017) Jet engine manufacturing (Marsh et al., 2013) 11/30/

21 Viruses Viruses are known to cause brain tumors in experimental animals, but most have been minimally evaluated in glioma Prior infection with varicella zoster virus (chicken pox) has been repeatedly associated with decreased odds of glioma Amirian et al., (2016) Limited and mixed evidence exists for other viral exposures, including: Influenza SV40 JC BK Chicken pox Glioblastoma Amirian et al., (2016) Wrensch et al., Neuro-oncology /30/

22 Other unproven environmental risk factors for glioma Air pollution Reproductive factors (e.g. parity, age at menarche, age at menopause) Exogenous hormone exposure (e.g. hormone replacement therapy, oral contraceptives) Prior cancer history Head trauma History of seizures Toxoplasma gondii Alcohol consumption Tobacco use Dietary nitrate consumption Vitamin use Cosmetics and hair dyes Sleeping pills Pain meds Aspirin, NSAIDS Antihistamines Wrensch et al., Neuro-oncology 2002; Ostrom et al., /30/

23 Limitations of case-control data for assessing glioma risk factors Many exposures that have been linked to glioma are difficult to measure, particularly when exposures are less recent EMF exposure, total cell phone use Several studies of potential glioma risk factors conducted using case-control study designs have produced results not replicable in cohort studies (Johansen et al., 2017) Ionizing radiation, sex hormone exposure It is likely that recall bias has inhibiting our ability to assess the relationship between 11/30/

24 THANK YOU! 11/30/

25 Key References 1. Amirian, E. S. et al. Approaching a scientific consensus on the association between allergies and glioma risk: A report from the glioma international case-control study. Cancer Epidemiol. Biomarkers Prev. 25, (2016). 2. Amirian, E. S. et al. History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC). Cancer Med. n/a-n/a (2016). doi: /cam Andersson, U. et al. Germline rearrangements in families with strong family history of glioma and malignant melanoma colon, and breast cancer. Neuro. Oncol. 16, (2014). 4. Bainbridge, M. N. et al. Germline mutations in shelterin complex genes are associated with familial glioma. J. Natl. Cancer Inst. 107, 2 5 (2015). 5. Benke, G. et al. Occupational solvent exposure and risk of glioma in the INTEROCC study. Br. J. Cancer 117, (2017). 6. Benson, V. S. et al. Mobile phone use and risk of brain neoplasms and other cancers: Prospective study. J. Immunol. 195, (2015). 7. Braganza, M. Z. et al. Ionizing radiation and the risk of brain and central nervous system tumors: a systematic review. Neuro.Oncol. 14, (2012). 8. Chapman, S., Azizi, L., Luo, Q. & Sitas, F. Has the incidence of brain cancer risen in Australia since the introduction of mobile phones 29 years ago? Cancer Epidemiol. 42, (2016). 9. Deltour, I. et al. Mobile phone use and incidence of glioma in the Nordic countries : consistency check. Epidemiology 23, (2012). 10. De Vocht, F., Burstyn, I. & Cherrie, J. W. Time trends ( ) in brain cancer incidence rates in relation to mobile phone use in England. Bioelectromagnetics 32, (2011). 11. Frei, P. et al. Use of mobile phones and risk of brain tumours: update of Danish cohort study. BMJ 343, d6387 (2011). 12. Grayson, J. K. Radiation exposure, socioeconomic status, and brain tumor risk in the US Air Force: a nested case-control study. Am J Epidemiol 143, (1996). 13. INTERPHONE Study Group. Brain tumour risk in relation to mobile telephone use: results of the INTERPHONE international case-control study. Int. J. Epidemiol. 39, (2010). 14. Inskip, P. D. et al. Radiation-related new primary solid cancers in the childhood cancer survivor study: Comparative radiation dose response and modification of treatment effects. Int. J. Radiat. Oncol. Biol. Phys. 94, (2016). 15. Johansen, C., Schüz, J., Andreasen, A.-M. S. & Dalton, S. O. Study designs may influence results: the problems with questionnaire-based case control studies on the epidemiology of glioma. Br. J. Cancer 1 8 (2017). doi: /bjc Kinnersley, B. et al. Quantifying the heritability of glioma using genome-wide complex trait analysis. Sci. Rep. 5, (2015). 17. Little, M. P. et al. Mobile phone use and glioma risk: comparison of epidemiological study results with incidence trends in the United States. Bmj 344, e1147 e1147 (2012). 11/30/

26 Key References, continued 18. Louis, L. M. et al. A prospective study of cancer risk among Agricultural Health Study farm spouses associated with personal use of organochlorine insecticides. Environ. Heal. 16, 95 (2017). 19. Marsh, G. M. et al. Long-Term Health Experience of Jet Engine Manufacturing Workers. J. Occup. Environ. Med. 55, (2013). 20. Melin, B. S. et al. Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors. Nat. Genet. 49, (2017). 21. Neglia, J. P. et al. New primary neoplasms of the central nervous system in survivors of childhood cancer: A report from the childhood cancer survivor study. J. Natl. Cancer Inst. 98, (2006). 22. Ostrom, Q. T. et al. The epidemiology of glioma in adults: A state of the science review. Neuro. Oncol. 16, (2014). 23. Ostrom, Q. T. et al. CBTRUS Statistical Report: Primary brain and other central nervous system tumors dsiagnosed in the United States in , Neuro. Oncol. 19 (S5), v1 v88 (2017). 24. Parent, M.-E. et al. Lifetime occupational exposure to metals and welding fumes, and risk of glioma: a 7-country population-based case control study. Environ. Heal. 16, 90 (2017). 25. Ruder, A. M. et al. Exposure to farm crops, livestock, and farm tasks and risk of glioma. Am. J. Epidemiol. 169, (2009). 26. Sadetzki, S. et al. Long-term follow-up for brain tumor development after childhood exposure to ionizing radiation for tinea capitis. Radiat. Res. 163, (2005) 27. Shete, S. et al. Genome-wide high-density SNP linkage search for glioma susceptibility loci: Results from the gliogene consortium. Cancer Res. 71, (2011). 28. Stupp, R. et al. Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. N. Engl. J. Med. 352, (2005). 29. Sun, X. et al. A variable age of onset segregation model for linkage analysis, with correction for ascertainment, applied to glioma. Cancer Epidemiol. Biomarkers Prev. 21, (2012). 30. Thakkar, J. P. et al. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol. Biomarkers Prev. 23, (2014). 31. Turner, M. C. et al. Occupational exposure to extremely low-frequency magnetic fields and brain tumor risks in the INTEROCC study. Cancer Epidemiol. Biomarkers Prev. 23, (2014). 32. Vila, J. et al. Development of a source-exposure matrix for occupational exposure assessment of electromagnetic fields in the INTEROCC study. J. Expo. Sci. Environ. Epidemiol. 27, (2017). 33. Wrensch, M., Minn, Y., Chew, T., Bondy, M. & Berger, M. S. Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro. Oncol. 4, (2002). 34. Yiin, J. H. et al. The upper midwest health study: a case control study of pesticide applicators and risk of glioma. Environ. Heal. 11, 39 (2012). 11/30/