epidemiologi kanker nasofaring (knf) dan epstein-barr virus (ebv)

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Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr virus (EBV) Demak L. Tobing R.S. Kanker Dharmais

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Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr virus (EBV), dr. Demak L Tobing, Sp. PK - R.S. Kanker Dharmais

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Page 1: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr virus (EBV)

Demak L. TobingR.S. Kanker Dharmais

Page 2: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

KNF dan EBV

• Ciri-ciri

–Rasial/Etnik

–Variasi Geografik

–Multifaktor etiologi :

• Lingkungan

• Virus

• Faktor resiko genetik

Page 3: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Tujuan :

– Highlight Epidemiologi KNF

–Pertanyaan yang belum terjawab

–Penelitian terhadap pertanyaan yang belum terjawab

Page 4: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Epidemiologi Diskriptif

Overview :

• Di Dunia merupakan kanker yang jarang

• Populasi tertentu : endemik

• Th. 2002 :

– angka kejadian : 80.000

–Kematian : > 50.000

–No 23 kasus baru kanker (Parkin DM dkk, 2002)

Page 5: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Sebaliknya, di Hong Kong– Kasus baru kanker No 4

• KNF :– Lapisan epitel nasofaring– Klasifikasi (WHO) :

Tipe histologik• Keratinizing squamous cell carcinoma (tipe I)• Nonkeratinizing carcinoma :

–Differentiated (tipe II)–Undifferentiated (tipe III)

Page 6: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• high-incidence area

–KNF tipe III ( > 95% )

–KNF tipe II (5%)

• low-incidence area

–KNF tipe I (predominant)

– Etiologi berbeda dari tipe II dan III

Zong YS dkk, 1983 ; Yu MC dkk, 1996 ; Vaughan TL dkk, 1996

Page 7: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Variasi geografik

–Nasofaring : KNF

• Pada umumnya angka kejadian berdasarkan usia (Laki-laki dan Wanita)

– < 1 per 100.000 tahun orang

• Angka kejadian meningkat pada populasi Cantonese (Cina sebelah selatan termasuk Hon Kong)

Page 8: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• intermediate rate

– Suku asli di Asia Tenggara

– Arctic

– Afrika Utara

– Timur Tengah

Page 9: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Tabel 1. Angka kejadian KNF berdasarkan usia pada populasi

Daerah dan populasi Tahun Angka kejadian (per 100.000 tahun orang)

Laki-laki Wanita

China and East Asia

China, Hong Kong 1993-1997 21.4 8.3

China, Taiwan 1997 8.9 3.4

China, Shanghai 1993-1997 4.2 1.5

China, Tianjin 1993-1997 1.7 0.5

China, Beijing 1993-1997 1.0 0.6

Japan, Osaka Prefecture 1993-1997 0.5 0.1

Korea, Seoul 1993-1997 1.0 0.3

Southeast Asia

Singapore, Chinese 1998-2002 12.5 4.2

Singapore, Malay 1998-2002 5.7 2.0

Singapore, Indian 1998-2002 1.5 0.1

Malaysia, Sarawak Bidayuh (native)

1996-1998 31.5 11.8

Malaysia, Sarawak Chinese 1996-1998 12.0 4.1

Malaysia, Sarawak Malay 1996-1998 7.8 1.9

Viet Nam, Hanoi 1993-1997 10.4 4.6

Viet Nam, Ho Chi Minh City 1995-1998 4.8 1.7

Thailand, Bangkok 1995-1997 4.5 1.6

Philippines, Manila 1993-1997 7.2 2.5

Arctic

Canada, Northwest Territories 1983-1997 9.2 6.0

Greenland, native 1992-2002 12.7 9.2

United States, Alaska native 1992-2002 7.8 2.4

Middle East/North Africa

Algeria, Algiers 1993-1997 2.7 1.3

Israel, Jews born in Africa or Asia 1993-1997 1.4 1.9

Israel, non-Jews 1993-1997 1.0 0.5

Kuwait, Kuwaitis 1994-1997 2.6 0.9

Kuwait, non-Kuwaitis 1994-1997 0.5 0.4

North America

Canada 1993-1997 0.8 0.3

United States, Whitek 1998-2002 0.4 0.2

United States, Blackk 1998-2002 0.8 0.3

United States, Hawaii Chinese 1993-1997 10.7 3.8

United States, Hawaii Filipino 1993-1997 3.5 1.5

United States, Hawaii native 1993-1997 3.6 0.9

United States, Los Angeles Chinese

1993-1997 7.6 2.4

United States, Los Angeles Filipino

1993-1997 3.7 1.6

Page 10: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Distribusi Jenis Kelamin dan usia

– Laki-laki 2 – 3 x > Wanita

– Daerah Low-risk population

• Usia ↗, angka kejadian meningkat

– Daerah high-risk population

– Puncak pada usia 50 – 59 th, kmd menurun

Page 11: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Age-specific incidence rates of NPC among White males and females in the United States, 1992 to 2003 (Devi BC et al, 2004)

Low-risk population

Page 12: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Age-specific incidence rates of NPC among males and females in Hong Kong,1980 to 1999 (Lee AW et al, 2003)

High-risk population

Page 13: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Paparan dengan agen karsinogenik (?) pada usia muda

• Sebaliknya

–Angka kejadian rendah (usia tua dan dewasa muda)

• Asia Tenggara

• Timur Tengah

• USA

–Agen karcinogenik (? umum)

Page 14: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Pola Rasial/Etnik• geographic regions

– high- or low-incidence areas,• Distribusi Rasial/Etnik tidak sama • Di Provinsi Cina bagian Tenggara :

– Guangdong : >20 per 100,000 tahun-orang pada pria.

– Angka pada penduduk berbahasa Cantonesemenunjukkan 2 x > dibandingkan yang berbahasa Hakka, Hokkien, dan Chiu Chau .

Li CC et al 1985

Page 15: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Sebaliknya

• Selangor Malaysia,

–Chinese residents

• Tertinggi adalah Cantonese,

• intermediate

– Khek,

• Terendah

– Hokkien dan Teochiu Armstrong RW et al, 1979

Page 16: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• the United States, angka tertinggi dan selanjutnya

1. Chinese Americans

2. Filipino Americans

3. Japanese Americans,

4. Blacks,

5. Hispanics6. Whites

Burt RD et al, 1992

Page 17: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Asia Tenggara

– Variasi : rasial dan campuran dengan Cina Selatan

• low incidence

– Singapore Indians (tidak bercampur dengan orang Cina)

• Higher incidence

– Thai,

– Macaonese,

• Melayu yang menikah dengan keturunan CinaHo HC, 1976.

Page 18: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Ho Chi Minh City

– Hanoi banyak etnik keturunan Cina

Japan and China,

– Cina Utara tinggi

– Japan rendah

• Nguyen MQ et al, 1998 ; Ho HC et al, 1976; Sawaki S et al, 1976 ; Parkin DM et al, 2002.

Page 19: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Penelitian Migrant

• Orang dari high- atau intermediate-risk area migrasi ke negara lower-risk, resiko KNF tetap tinggi

• Orang Cina Selatan tinggal di Singapur, Malaysia dan Jepang, angka KNF berbeda dengan Orang Cina Selatan asli

Parkin DM, 2002 ; Armstrong RW, 1979 ; Sawaki S, 1976

Page 20: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Tetap tinggi ( berasal dari High-risk area)

• Orang Afrika Utara bermigrasi ke Israel. (28). Angka kejadian tinggi meskipun tinggal di Israel

• Orang Cina di USA : 10 – 20 x lb tinggi dibandingkan orang kulit putih dan hitam

Tabel 1

Page 21: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Angka Kejadian

– rendah pd Chinese migrants ke

• United Kingdom

• Australia

• Lama tinggal di negeri Barat

–Meningkat

• White males lahir di Cina atau Filipina dibandingkan yang lahir di USA

Warnakulasuriya KA et al 1999; McCredie M et al, 1999; Buell P et al.1974;Buell P, 1973

Page 22: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• French origin males lahir di North Africa, dibandingkan dengan yang lahir di southernFrance

• Penurunan nyata bila Chinese migrasi ke Barat (overestimated)

– Laporan tidak memperhitungkan campuran highand low-risk migrants pada populasi asal.

Jeannel D et al, 1993

Page 23: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Sebab

– cancer registries generally do not record data on ethnic subgroup, rates in Chinese ethnic subgroups cannot be accurately estimated.

– traditional Asian lifestyle (berhubungan dengan peningkatan KNF)

– individuals who migrate overseas : inherently lower-risk group.

Angka kejadian KNF pada migran tidak dapat secara langsung dibandingkan dengan yang dari asal negrinya.

Page 24: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Secular Trends.

• Bukti sejarah Cina, Mesir (42) dan Iran (43),

–KNF bukan modern environmental hazards

–genetic and/or stable environmental risk factors (berabad-abad)

Ho HC et al, 1976 ; Wells C, 1963 ; Wells C, 1940

Page 25: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Berdasarkan modern cancer registry data, angka kejadian KNF tetap tinggi di Asia Tenggara

• Penurunan angka kejadian KNF di Hong Kong sejak th 1970 an

Parkin DM et al, 2002 ; Lee AW et al, 2003 ; Muir C et al, 1987 ; Waterhouse J et al,1982 ; Parkin DM et al, 1992 ; Parkin DM et al, 1997

Page 26: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Perubahan ekonomi penduduk

– Taiwan sejak 1980s (48), Singapore Chinese sejak 1990s (1, 44-47, 49). Hong Kong sejak pertengahan th 1940

Muir C et al, 1987 ; Waterhouse J et al, 1982 ; Parkin DM et, 1992 dan 1997

Page 27: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Sebaliknya, angka kejadian meningkat

– Singapore Malays antara 1968 and 1997,

– Tetap tinggi pada laki-laki di Cangwu county dan menetap atau sedikit meningkat di Southeastern China antara 1978/1983 dan 2002.

Wang H et al, 2006 ; Sun LM et al, 2005

Page 28: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Faktor Resiko

• Epstein Barr virus (EBV)

– Laten, 90% populasi dunia

–Hong Kong

• 80% anak-anak usia 6 th, usia 10 th serokoversi 100% (55)

– Infeksi subklinik ----- berbagai keganasan termasuk KNF

Page 29: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

– Transmisi

• Saliva

• Negara berkembang terjadi pada usia dini

–Kepadatan penduduk

–Higienik kurang

–Hidup di Limfosit B, epitel nasofaring dan orofaring

Rickinson AB et al, 2001; Kangro HO et al, 1994 ; IARC, 1997 ; Mueller NE et al, 1996

Page 30: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• KNF ----EBV

– Sejak th 1996 (60)

– Express antibody (1970 confirmed) meningkat pada KNF dibandingkan kontrol (61)

– Antibodi (62-74)

• IgG dan IgA (EBV VCA, EBV EA)

• IgG (EBV EBNA 1 dan 2)

• IgA (EBV VCA p18 dan EBNA1)

• Antibodi thd EBV-specific DNAse

Page 31: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Antibodi IgA (peningkatan)(76-84)

– Mendahului pertumbuhan tumor

– Tumor burden

– Remission

– Recurrence

• IgA EBV VCA

– Screening (high-risk population) (85-90) kombinasi dengan antibodi anti-EBV DNAse (73, 91)

Page 32: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Circulating cell-free EBV DNA

– Pada KNF > kontrol (92-95)

– Korelasi dengan Stage dan prognosis (92-97)

– Prospective studies : predisease level (belum)

• Further :

– EBV DNA

– EBV RNA

– Gene product dalam sel tumor

Page 33: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• International pattern KNF– Distribusi EBV strain

– Prototipe B95.8 EBV strain

– LMP1 – variasi

• amino terminal

– Loss of a XhoI restriction site (southern and nothern Chinese, Malays, Alaska dan US)

• Carboxyl terminus (Chinese NPC)

– 33 bp repeat element

– Insersi : 15 bp pada the third repeat element

– Delesi : 30 bp pada carboxyl terminus

Page 34: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Variasi LMP1 menyebabkan KNF lebih agresif ?

• Variant (deleted) = peningkatan resiko KNF ?

• LMP1 variant mempengaruhi immune selection ? (reduced CTL response)

Well-designed epidemiologic studies of risk

associations with EBV variants

Page 35: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Pengumpulan bukti-bukti bahwa peran EBV sebagai penyebab KNF (56) ;

• early-life infection, tipikal pada high-incidence areas (55, 135) ----- critical.

• EBV sendiri tidak cukup menyebabkan KNF, karena sebagian besar orang dewasa di dunia telah terinfeksi EBV.

• a small proportion of individuals develop NPC.

Page 36: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Bagaimana ?

– environmental

– Faktor genetik

Juga berkontribusi pada resiko KNF !

Page 37: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Salt-Preserved Fish dan makanan lain

• Konsumsi salt-preserved fish,

– Penelitian pada populasi Cina

– Resiko relatif KNF bila makan ikan asin tiap minggu dibandingkan yang tidak atau jarang mengkonsumsi : 1.4 sampai 3.2/100.000 th orang

– Konsumsi tiap hari : 1.8 sampai 7.5 /100.000 th orang (136-141).

Page 38: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Preserved food lain

– Daging

– Telur

– Buah

– sayur

Page 39: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Tobacco, Other Smoke, and Alcohol

• The majority of case control studies examining cigarette smoking and risk of NPC in a variety of populations reported an increased risk of 2-to 6- fold (9, 39, 40, 73, 142, 172-181)

• some studies found no association (24, 38, 74, 137,

141, 148, 154, 183-186).

Page 40: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• The discrepancy in findings may be due in part to differences in study design and/or exposure assessment

• several of the studies reporting a positiveassociation were conducted in low- or intermediate-incidence populations (9, 142, 173,

175-178, 180).

Page 41: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• U.S. study

– An estimated two thirds of type I NPC was attributable to smoking, but risk of type II or III NPC was not associated with smoking (9)

– the declining prevalence of smoking (187) may explain the recent decreasing trend in the incidence of type I NPC in the United States (52).

Page 42: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

– Some researchers have suggested that the high incidence of NPC in southern Chinese and North Africans is caused by smoke from wood fires in chimneyless homes (151, 168, 189). ( five times)

– Studies examining burning incense orantimosquito coils have been similarly equivocal, with two studies finding up to a 6-fold excess risk of NPC with use of antimosquito coils (177, 185)

Page 43: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

– Alcohol consumption also seems not to be associated with NPC risk, because most (35, 38, 39, 73, 74,

141, 148, 154, 172, 173, 180, 183-185), but not all (9, 139, 175), case-control studies were negative.

– Inconsistent findings may be due to differences in study characteristics, as well as chance or confounding.

Page 44: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Herbal Medicines

– Tradisional

– 2 sampai 4 kali resiko KNF

– Aspek lain ?!

– induce viral lytic antigen expression by activating EBV in vitro (194-197)

• Herbal drugs yang tinggi dan titer anti EBV EBNA (193)

– suggesting a direct proliferative effect of herbal medicines on EBV-transformed cells

Page 45: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Occupational Exposures

• Occupational exposure to fumes, smokes, dusts, or chemicals overall was associated witha 2- to 6-fold higher risk of NPC in some but not all studies (73, 154, 174, 177, 184)

• exposure to formaldehyde is supported by experimental observations in rodents (201, 202), but epidemiologic evidence in humans islimited, especially for endemic types II and III.

Page 46: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Three case-control studies observed a 2- to 4-fold excess risk of NPC (177, 199, 203), and a U.S. study found an increased risk of type I but not type II or III NPC (204),

• exposure to wood solvents and preservatives, such as chlorophenols, may also be involved (179, 181, 231)

Page 47: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Familial Clustering

• Familial aggregation of NPC has been widely documented in high-incidence (190, 250-253), intermediate-incidence (254-257), and low-incidence populations(258-267).

• result from shared genetic susceptibility, shared environmental risk factors, or both

• the case of NPC, genes and environmental exposures likely play a combined role

Page 48: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

– a complex segregation analysis of familial NPC in southern China (268), multiple genetic and environmental factors, rather than a single majorusceptibility gene, seemed most likely to explain the observed pattern of inheritance.

– In epidemiologic studies, the excess risk was generally 4- to 10-fold among individuals with afirst-degree relative with NPC, compared with those without a family history (73, 137, 141, 174, 180,

269-274).

Page 49: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Human Leukocyte Antigen Genes

• Genes conferring susceptibility to NPC

• encode proteins required for the presentation of foreign antigens, including viral peptides, to the immune system for targeted lysis

Page 50: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Proposed causal model of endemic (types II and III) NPC

Page 51: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Because virtually all NPC tumors contain EBV, individuals who inherit HLA alleles with a reduced ability to present EBV antigens may have an increased risk of developing NPC

• whereas individuals with HLA alleles that present EBV efficiently may have a lower risk (276, 277).

Page 52: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Some HLA alleles have been consistently associated with NPC risk.

• In southern Chinese and other Asian populations

– HLA-A2-B46 (252, 277-284) and B17 (281, 282, 285-287)

were generally associated with a 2- to 3-fold increase in NPC risk.

Page 53: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• In contrast, 30% to 50% lower risk of NPC was found in association with HLA-A11 in both Chinese and Whites (277, 281-283, 287, 288), B13 in Chinese (279, 282), and A2 in Whites (288, 289).

Page 54: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

A meta-analysis of studies in southern Chinesepopulations

– the combined evidence suggested a positiveassociation of NPC risk with HLA-A2, B14, and B46,

– and an inverse association with HLA-A11, B13, and B22 (290).

Page 55: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Reported associations between NPC risk and other HLA genes, including class II alleles, must be interpreted with caution due to the probability of chance findings based onmultiple comparisons.

Page 56: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Other Genetic Variation

• Several genetic polymorphisms and chromosomal abnormalities have been identified by epidemiology studies searching for NPC susceptibility loci

• A few studies examined genetic variation in genes involved in metabolism of nitrosamines, tobacco, and other contaminants.

Page 57: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Polymorphisms in

– cytochrome P450 2E1 (CYP2E1). (293-295)

– CYP2A6 (296)

– the absence of glutathione S-transferase M1 (GSTM1) (97-299) and/or GSTT1 (298) were

• associated with 2- to 5-fold increased risk of NPC

Page 58: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• In Taiwan, a variant of CYP2E1 was evenly distributed between familial and nonfamilial NPC cases (270), with no association betweenNPC risk and genetic polymorphisms in CYP1A1, GSTM1, GSTT1, GSTP1, or N-acetyltransferase 2 (NAT2) (300).

Page 59: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Among Cantonese subjects, no association was found with genetic variation in CYP2A13 (301).

• In Thailand (302) and China (303), polymorphisms in the polymeric immunoglobulin receptor(PIGR), a cell surface receptor proposed to mediate EBV entry into the nasal epithelium, were associated with increased risk of NPC

Page 60: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• Genetic changes

– studies of loss of heterozygosity in NPC tumors detected a high frequency of allelic loss, especially on chromosomes 3p, 9p, 11q, 13q, and 14q (305-

315)

– A recent meta-analysis of comparative genomic hybridization results revealed several genomic ‘‘hotspots’’ where chromosomal losses and gains have consistently been detected in NPC tumors (316)

Page 61: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

• In addition, tumor-suppressor genes, such as

– Ras association domain family 1A (RASSF1A) (317-

321),

– cyclin-dependent kinase inhibitor 2A (CDKN2A, p16/INK4A) (318-320, 322),

– and immunoglobulin superfamily member 4 (IGSF4, TSLC1) (321, 323, 324)

may frequently be inactivated in NPC tumors by promoter methylation

Page 62: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

Jakarta Minimum Cancer Incidence (Coverage 70% )79 Hospitals. 2 Private Clinics, 90 Pathology Laboratories,

44 Municipals Primary health Care (as a coordinator of 301 Primary Health Care in District area).

Page 63: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)

2.74

2.84

2.99

3.89

6.23

7.47

9.57

10.06

12.95

13.75

0.00 2.00 4.00 6.00 8.00 10.00 12.00 14.00

percent

Soft Tissue

Skin

Prostate Gland

Oral Cavity

Liver

Leukemia

Lymph Nodes

Colorectum

Nasopharynx

Bronchus and Lung

Top 10 Malignancy in Dharmais NCC

in Male 2005-2007

2.49

2.85

2.87

3.05

3.26

3.54

3.75

5.64

17.96

40.25

0.00 10.00 20.00 30.00 40.00 50.00

percent

Corpus Uteri

Bronchus and Lung

Nasopharynx

Leukemia

Lymph Nodes

Thyroid Gland

Colorectum

Ovary

Cervix Uteri

Breast

Top 10 Malignancy in Dharmais NCC in

Female 2005-2007

Page 64: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)
Page 65: Epidemiologi Kanker Nasofaring (KNF) dan Epstein-Barr Virus (EBV)