KANKER AKIBAT KERJA

Dr. Luis Yulia, MKKK

FK UNIBA
26 NOVEMBER 2015
KANKER AKIBAT KERJA
 Merupakan penyebab kematian.
 Disebabkan oleh pajanan terhadap zat
karsinogen di tempat kerja
CARCINOGENESIS –
OVERVIEW
 Neoplasia – Definitions
 Hypotheses of the Origin of Neoplasia
 Agents Causing Neoplasia
 Chemical Oncogenesis
 Radiation Oncogenesis
 Viral Oncogenesis
 Nutritional Oncogenesis
 Hormonal Oncogenesis
 Genetic Oncogenesis
CARCINOGENESIS
AGENTS CAUSING NEOPLASM
 Carcinogens – substances known to cause
cancer or produces an increase in incidence
of cancer in animals or humans
 Cause of most cancers is unknown
 Most cancers are probably multifactorial in origin
 Known carcinogenic agents constitute a small
percentage of cases
 Unidentified ‘environmental’ agents probably
play a role in 95% of cancers
KARSINOGENISITAS
 ANKYLATING AGENTS
 METALS
 ASBESTOS
 VYNIL CHLORIDE
 STEROID
 FAKTOR FISIK : RADIASI
KONVERSI METABOLIK
 Bbrp seny hanya bersifat karsinogen
setelahdiolah oleh enzim2
host;amine,amide,nitro setelah diolah mjd
bentuk n-hidroxy bersifat karsinogen;
 Benzo-a-pyrene: mjd karsinogen stlh diolah
oleh enzim-enzim mikrosome (P-450)mjd btk
epoxy, phenols, dan dihydrodiols;
 Hampir semua molekul karsinogen bersifat
elektrofilik ( mol kekurangan elektron)
PENGARUH TEHADAP DNA
 Karsinogen mampu berikatan dengan DNA
host
 Kerusakan pada DNA (materi genetik)
 Gangguan fungsi sel al proliferasi
 Karsinogen umumnya adalah mutagen
(perubahan pd materi genetik)
 Mekanisme DNA repair dpt mereparasi bgn yg
rusak (DNA Adduct) dan dibuang keluar.
MULTI STAGE ACTION
 Sifat sel tumor: monoclonal;dari 1 sel yg
ganas berproliferasidan metastasis
 Periode laten panjang
 Sifat Inisiator : genotoxic
 Dibutuhkan promotor (via faktor non DNA)
baru menyebabkan kearah keganasan.
Beberapa bahan inisiator dan promotor
(karsinogen komplit) misal Poly Aromatic
Hydrocarbon (PAH)
KANKER AKIBAT KERJA
 Di negara maju dari 700-1,000 pekerja yg
meninggal – 30-40% disebabkan kanker – terutama
kanker paru
 Kanker paru akibat asbestos, asap diesel , asap
rokok…
 Mesothelioma karena asbestos
 Leukemia akibat benzene..
 Kanker kandung kemih dari pewarna, cat,
solvents….
KLASIFIKASI ZAT KARSINOGEN
DALAM 5 GRUP (IARC) :
 Group 1 : Proven human carcinogens (based on
epidemiological studies among workers with long
exposure)
 Group 2A: Probable human carcinogens (evidence
from animal studies which are relevant to human
exposure)
 Group 2B: Possible human carcinogens (evidence of
significant increase in cancer incidence in more
than one animal species or strains)
 Group 3 : Agents are not classifiable as
carcinogenic to humans
 Group 4 : Agents probably not carcinogenic to
human
 Carcinogens - IARC Overall
Evaluation Categories
Group Interpretation Number

Group 1 Carcinogenic to humans 100

Group 2 2A Probably carcinogenic to humans 66

2B Possibly carcinogenic to humans 241

Group 3 Not classifiable as to carcinogenicity to 497

humans
Group 4 Probably not carcinogenic to humans 1
IARC klasifikasi - Contoh
Bahan kimia IARC klasifikasi
Etanol (alkohol diminum) Group 1
Mineral oils (untreated) Group 1
Benzene Group 1
Formaldehyde Group 1
Acrylonitrile Group 2A
Dichloromethane Group 2A
Styrene Group 2B
Methyl methacrylate Group 3
(monomer)
 ACGIH
CARCINOGEN CLASSIFICATION
A1 — Confirmed Human Carcinogen
The agent is carcinogenic to humans

A2 — Suspected Human Carcinogen

Limited evidence of carcinogenicity in humans and sufficient evidence of
carcinogenicity in experimental animals with relevance to humans.

A3 — Confirmed Animal Carcinogen with Unknown Relevance to Humans

The agent is carcinogenic in experimental animals at a relatively high
dose, by route(s) of administration, at site(s), of histologic type(s), or by
mechanism(s) that may not be relevant to worker exposure.

A4 — Not Classifiable as a Human Carcinogen

Agents that cause concern that they could be carcinogenic for humans but
which cannot be assessed conclusively because of a lack of data.

A5 — Not Suspected as a Human Carcinogen

The agent is not suspected to be a human carcinogen.
 IS
Acquired environmental factors

ES
chemicals ,radiation ,viruses
EN
OG

Changes in genome Genetic

of somatic cells factors
TH
PA

Activation of growth Inactivation of cancer

promoting oncogenes supressor genes

Expression all altered gene products

and loss of regular gene products

MALIGNANT NEOPLASM
GAMBARAN KLINIS
 Gambaran klinis khas kanker
 Gambaran histopatologi tidak dapat
dibedakan antara penyebab akibat kerja atau
bukan.
 Kanker mempunyai periode masa laten yang
lama sehingga merupakan tantangan untuk
mencari riwayat pajanan dan hubungan
kausal.
DIANOSIS DIFFERENTIAL
 Singkirkan penyebab kanker bukan dari
tempat kerja, seperti :
 A. riwayat keluarga (genetic predisposition)
 B. faktor lifestyle (rokok, diet, pajanan
terhadap sinar matahari yang berlebihan)
 C. Penggunaan beberapa obat-obatan ;
seperti estrogen ( mammae, ovarium dan
uterus) dan tamoxifen (ca uterus dan ca
endometrium)
KRITERIA DIAGNOSIS KAITAN
DG PEKERJAAN
 Riwayat pajanan yang lama pada pekerjaan
 Dicurigai pajanan tempat kerja jika muncul
pada pekerja usia muda dan bila kasus jarang
dijumpai
 Dokumen personal/medical record pekerja
 Monitoring pajanan di tempat kerja
 CARCINOGENS AND ASSOCIATED EXPOSURES

Cancer Type of Exposure Situations/At-risk Exposure

Involving Carcinogens
Bladder 4 • Rubber and tyre manufacturing
Aminobiphenyl
Arsenic* • Wood preservation
• Use of pesticides
• Manufacture of glass,
semiconductors, alloys, pigment, anti-
fouling paints
Benzidine • Manufacture of pigments and dyes

Blood Benzene* • Petrochemical industry

(Leukaemia) • Refinery
• Laboratory and testing work
involving the use of benzene (e.g.,
vehicle workshop, petrol stations)
• Bulk storage of petrol and related
products
Ionising • Use of radioactive isotopics or
radiation irradiation apparatus, such as X-ray
 CARCINOGENS AND ASSOCIATED EXPOSURES

Cancer Type of Exposure Situations/At-risk Exposure

Involving Carcinogens

Lung Arsenic* • Wood preservation

• Use of pesticides
• Manufacture of glass, semiconductors, alloys,
pigment, anti-fouling paints

Asbetos* • Construction and demolition of buildings containing

asbestos roofings, rubbish chutes
• Ship breaking and repair where asbestos is used for
insulation of boilers, pipes
• Repair and replacement of asbestos brake linings by
car and bus mechanics

Beryllium • Manufacture of nuclear devices, satellite and radar

systems, aircraft brushings and bearings in the
defence and aeronautical industry
 CARCINOGENS AND ASSOCIATED EXPOSURES

Cancer Type of Exposure Situations/At-risk Exposure

Involving Carcinogens
Lung Cadmium* • Manufacture of nickel-cadmium battery,
jewellery, certain fungicides, pigments and dyes
• Waste treatment
• Smelting and refining of ores containing
cadmium
• Silver brazing using cadmium-containing alloys
• Plastic industry (during compounding of
polyvinyl chloride)
• Cadmium electroplating
• Automobile and aircraft industries
Chromium • Chromium metal plating
(hexavalent) • Manufacture of pigments and dyes
Nickel • Stailess steel production
• Manufacture of batteries
Bis • Chemical industry
(chloromethyl)
ether
 CARCINOGENS AND ASSOCIATED EXPOSURES
Cancer Type of Exposure Situations/At-risk Exposure
Involving Carcinogens
Lung Vinyl Chloride • Rubber and plastic manufacturing
(VCM)* • Storage of VCM
• Sampling and analysis of VCM
Liver Arsenic* • Wood preservation
(Angiosarcoma) • Use of pesticides
• Manufacture of glass, semiconductors,
alloys, pigment, anti-fouling paints

Vinyl Chloride • Rubber and plastic manufacturing

(VCM)* • Storage of VCM
• Sampling and analysis of VCM
 CARCINOGENS AND ASSOCIATED EXPOSURES

Cancer Type of Exposure Situations/At-risk Exposure

Involving Carcinogens
Pleural, Asbestos* • Construction and demolition of buildings
Peritoneum containing asbestos roofings, rubbish
(Mesothelioma) chutes
+ • Ship breaking and repair where asbestos
is used for insulation of boilers, pipes
• Repair and replacement of asbestos
brake linings by car and bus mechanics
Nasal Cavities Chromium • Electroplating
and Paranasal (hexavalent) • Production and welding of stainless steel
Sinuses parts

Nickel • Stainless steel production

• Manufacture of batteries
Wood dust • Woodworking
 Contoh oil shale

Coke

Tar batubara Pitch batubara

CARCINOGENESIS
AGENTS CAUSING NEOPLASM
UV Radiation
 Solar UV radiation associated with skin

cancers – squamous CA, basal cell CA,

malignant melanoma
 Fair-skinned and elderly are

susceptible
 UV light is believed to induce cross-

linkages between DNA molecules and

CA occurs when repair mechanisms are
not efficient
CARCINOGENESIS
AGENTS CAUSING NEOPLASM
X-ray radiation
 Earlier use of X-rays caused skin
cancer, leukemia and papillary thyroid
CA
 Radiotherapy causes raditation-

induced malignancy 10-30 yrs later –

usually sarcomas
 Diagnostic X-rays are considered to

have no increased risk except in

abdominal x-rays which increase
incidence of leukemia in the fetus
CARCINOGENESIS
AGENTS CAUSING NEOPLASM
 Radioisotopes
 Osteosarcoma common among factory
workers who use radium-containing
paints
 Radioactive mineral mining in Europe

and USA associated with lung cancer

 Thorium increases risk of liver cancer –

hepatocellular, angiosarcoma,
cholangiocarcinoma
 Radioactive iodine – increased risk of

cancer 15-25 years later

CARCINOGENESIS
AGENTS CAUSING NEOPLASM
 Nuclear Fallout
 Hiroshima, Nagasaki (atomic blasts)
 Marshall islands (atmospheric testing of nuclear divide
containing radioactive iodine)
 Chernobyl, 1986
MESOTHELIOMA
 Mesothelioma diffuse di peritoneum merupakan tanda
khas pajanan asbestos
 Masa laten : 3 tahun atau lebih
 Asbestos digunakan dalam semen, tekstil dan bahan atap
rumah
 Pekerja yang terpajan : pekerja konstruksi, plumber,
galangan kapal dan pekerja listrik
 Semua jenis serabut asbestos dapat menyebabkan
mesothelioma
 Crocidolite paling berbahaya
 Tidak ada interaksi antara merokok & pajanan asbestos
dalam timbulnya mesothelioma.
ASBES  KANKER PARU, MESOTELIOMA, ASBESTOSIS,
KELAINAN PLEURA
LEUKEMIA
 2 jenis yg disebabkan pekerjaan :
Leukemia mieloid akut dan kronik
 Penyebab :
Radiasi pengion dengan masa laten 15-
20 th
Benzene
Obat anti-neoplastik : alkylating agent
INVESTIGASI UNTUK
MENENTUKAN KAITAN DENGAN
PEKERJAAN
 Riwayat pajanan terhadap kelompok grup 1
IARC di tempat kerja
 Meminta data monitoring perusahaan
terhadap hazard di tempat kerja, apakah
melebihi batas pajanan yang ditetapkan oleh
ACGIH
 Cari korelasi kanker dengan masa laten;
durasi pajanan minimal dan level pajanan.
Masa laten berkisar 5 sp 30 atau 40 tahun,
tergantung jenis kanker.
 Singkirkan penyebab non okupasi.
EVALUASI KARSINOGENITAS
KIMIA
 Penelitian Epidemiologi populasi manusia
yang terpajan – paling dapat diandalkan
 Penelitian kesamaan struktur terhadap
karsinogen yang telah diketahui
 Uji Laboratorium
 Pada hewan
 Uji karsinogenitas In vitro dari sel yang dikultur
 PENTINGNYA EPIDEMIOLOGI
KANKER AKIBAT KERJA
 Hampir separuh karsinogen manusia yang diketahui
merupakan senyawa yang terutama didapatkan pada
lingkungan kerja
 Walaupun sementara ini seberapa besar peranannya
masih dipertanyakan, banyak kasus kanker tidak
diragukan lagi disebabkan pajanan kerja
 Sekali dapat diidentifikasi, tindakan pengendalian
sering dapat dilakukan
 Penemuan karsinogen di tempat kerja mempunyai
banyak manfaat di luar pabrik
 Memberikan dasar untuk kompensasi korban
 Memberi informasi dalam memahami karsinogenesis
 STRATEGI MENEMUKAN
KARSINOGEN
 Epidemiologi

 Eksperimen binatang (toksikologi)

 Efek biologi lain

Mutagenesis
Genotoksisitas
Dll.
PUNCAK GUNUNG ES / ICEBERG
 Kebanyakan karsinogen kerja yang diketahui
didapat secara kebetulan

 Apakah ini merupakan puncak gunung es ?

 Apakah kemungkinan besar masih terdapat

banyak lagi karsinogen kerja ?
PENATALAKSANAAN
 Semua penderita penyakit kanker perlu dirujuk
ke RS guna penanganan lebih lanjut.
 Untuk perusahaan disarankan sbb:
 Review RA (risk assessment) tempat kerja &
mengurangi pajanan, engineering controls, akses
terbatas, PPE
 Substitusi dgn bahan non karsinogenik
 Cari persyaratan MCU sesuai dg peraturan yang
berlaku dan monitoring tempat kerja
 Pencatatan & pelaporan TK yang terpajan
karsinogen minimal 10 tahun.
PENCEGAHAN
1.Tidak mengintroduksi karsinogen ke tempat
kerja
2.Menyingkirkan karsinogen yang telah diketahui
dari tempat kerja
3.Mengurangi tingkat pajanan
4.Mengurangi aktivitas berbahaya
5.Meningkatan perlindungan pekerja
6.Mendaftarkan pajanan terhadap karsinogen
tempat kerja
7.Pengendalian internasional
Thank you for your
attention