Familial Aggregation of Nasopharyngeal Carcinoma in Taiwan

1. Familial Aggregation of NasopharyngealCarcinoma in Taiwan • 長庚醫院耳鼻喉頭頸外科部 R5 蕭仁豪 • 指導教授: 黃祥富 教授 ALLPPT.com _ Free PowerPoint Templates, Diagrams and Charts

2. Background

5. Studies of immigrant populations Genetic factors Lifestyle factors • Chen CJ, You SL, Lin LH, Hsu WL, Yang YW. Cancer epidemiology and control inTaiwan: a brief review. Jpn J ClinOncol 2002;32(Suppl):S66–81. • Sun LM, Epplein M, Li CI, Vaughan TL, Weiss NS. Trends in the incidence ratesofnasopharyngeal carcinoma among ChineseAmericans living in Los AngelesCountyand the San Francisco metropolitan area, 1992–2002. Am J Epidemiol2005;162:1174–8.

6. Literature Review 01 02 Friborg J, Wohlfahrt J, Koch A, Storm H, Olsen OR, Melbye M. Cancer susceptibility in nasopharyngeal carcinoma families–a population-based cohort study. Cancer Res 2005;65:8567–72. 03 OR 8 5.5 4-20 FH: control =1019/9662 High familial tendency for NPC ( adjusted hazard ratio) Greenland and Denmark (766 first-degree relatives/134 patients) First-degree family history of NPC case control study Hsu WL, Yu KJ, Chien YC, Chiang CJ, Cheng YJ, Chen JY, et al. Familial tendency and risk of nasopharyngeal carcinoma in taiwan: effects of covariates on risk.AmJ Epidemiol 2011;173:292–9

7. >99.5% Stable ethnic composition 01 02 Bias from previous studies: limited proband Han ethnic group + aborigines 2013

8. Patients and Methods

10. Study population >99.5% Diagnosis of NPC • Identify NPC patients : (ICD-9:147) • Validation study: compared with National Cancer RegistryPPV: 0.92 1997-2013

11. Statistical analysis Marginal model Intrafamilial clustering bias (age and gender effect on the onset of cancer ) Polygenic liability model Marginal model Cox proportional hazards model 01 02 03 polygenic liability model Adjusted RR ( age, sex,socioeconomicfactors, and family size )

12. Results

13. Prevalence of NPC in individuals with affected first-degree family members vs. the general population > >

16. Compared with the general population RR With oneaffected first-degree relative With more than two affected first-degree relatives 42.18 (95% CI, 14.17–125.56) > 4.49 (95% CI,3.65–5.53)

17. Heritability of NPC

18. Discussion

19. The RR of affected relatives of NPC patients was 4.61(95% CI, 3.76–5.65) 01 Cantonese populations reportedly have higher risks of NPC than other ethnicities Shanmugaratnam K. Variations in nasopharyngeal cancer incidence amongspecific Chinese communities (dialect groups) in Singapore. IARC SciPubl1978:191–8. 02 03 Familial NPC in southern China was found to be relatedto multiplegenetic and environmental factors rather than asingle major susceptibility gene Jia WH, Collins A, Zeng YX, Feng BJ, Yu XJ, Huang LX, et al. Complex segregationanalysis ofnasopharyngeal carcinoma in Guangdong, China: evidence for amultifactorial mode of inheritance (complexsegregation analysis of NPC inChina). Eur J Hum Genet 2005;13:248–52.

20. 17 108 1077 • Ng WT, Choi CW, Lee MC, Chan SH, Yau TK, Lee AW. Familial nasopharyngeal carcinoma in Hong Kong:epidemiologyand implication in screening. FamCancer 2009;8:103–8 • NPC patients tended to be younger ( 35.5 years Vs. 39.0 years) at thetime of diagnosis (p < 0.0001)

21. Genetic investigation NPC is closely linked to EBV infection, and HLA alleles are critical for the proper presentation of viral antigens to the immune system Multiple chromosome 6p susceptibility loci Genome-wide linkage analyses 01 02 03 X-linked recessive mutations Male predominance GABBR1 NEDD9 Environmental+ genetic factors => genetic susceptibility to NPC Noconclusive results => Heterogeneity among the study populations + multi-factorial etiology HLA antigen in 6p22, D4S3002 in 4p15.1-q12 D3S3624 in 3p21.31-21.2 D5S2021 in 5p13.1 04 05 06 Your Text Here

22. The importance of screening among those with NPC history • As demonstrated by Ng, cases detected during screening are at an earlier tumor stage, and the patients tend to be younger. • As technology advances in examination modalities, screening procedure are more and more easily accessible. • The success of a screening program depends heavily on the existence of a well-defined population at risk. • Screening should begin after the age of 30 years, asthe majority of familial NPC cases occur in persons older than30 years of age • Loh KS, Goh BC, Lu J, Hsieh WS, Tan L. Familial nasopharyngeal carcinoma in acohort of 200 patients. Arch Otolaryngol Head Neck Surg 2006;132:82–5. • Our study : the youngest patient witha first-degree relative with NPC was <20 years of age=>screening should be performed prior to the age of 30 years

23. Liability threshold model Spouse:13.9 % Shared environment Sibling: Shared environment +Genetic factors Hereditary : 61.3 % KuoCF, Grainge MJ, Valdes AM, See LC, Luo SF, Yu KH, et al. Familialaggregation of systemic lupus erythematosus and co-aggregation ofautoimmune diseases in affected families. JAMA Int Med 2015;175:1518–26.

24. Conclusion Having an affected first-degree relative is a strong and easily recognizable risk factor for developing NPC. This strong familial aggregation suggests the need for regular screening of first-degree relatives of NPC patients, particularly in endemic regions.

25. Thank you for your attention

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