Up-serge, pathogenesis and feasible preventive measures

1. 2018 writing fellow @ Johannesburg Institute of Advanced Studies
1st of the 2018 JIAS Writing Fellows Seminar Series
GEOFFREY MAIYOH, PhD
Molecular Biosciences and Bioengineering,
University of Hawaii at Manoa, Honolulu, USA
Department of Medical Biochemistry,
School of Medicine, Moi University,
Eldoret, Kenya
Upsurge of Cancer in Kenya: Risk factors, Pathogenesis
and Feasible Preventive Measures

2. KENYA - FACTS
 East African Nation
 Capital Nairobi (3.1)
 Pop: 48.5 million
 Swahili/ English
 42 tribes (many dialects)
 47 County governments
 Economy: Agriculture ~
25.4 percent of GDP
 Currency KSh (7-10 to R)

3. Major regions and Ethnic background

4. FEW PRIDES OF KENYA
 Wildlife
 Top athletes - distance running
 Pioneered the mobile pay technology – MPESA (Did not work in SA!)
http://www.news24.co.ke/business/news/kenya-leads-africa-in-mobile-pay-technology-20120509
 Internet connectivity (low cost and high band width)
http://www.diplomateastafrica.com/diplomatic-news/1631-kenya-leads-in-connectivity-in-africa
 2% GDP allocation to research – NRF (great news for people in academia)
www.researchfund.go.ke/
 Eco-tourism – Eco-lodges (https://www.frommers.com/destinations/kenya/the-best-ecolodges--
wilderness-resorts)

5. March 1, 2018
Kinsley 4
Ethan 8
Ryan 6
Jenniffer
My family

6. My Academic Background
 Bachelor of Science in Biochemistry and Chemistry
from Egerton University, Njoro, Kenya, 1999
 Doctor of Philosophy in Molecular Biosciences and
Bioengineering from the University of Hawaii at
Manoa, 2007

7. Post PhD Employment
 Moi Teaching and Referral Hospital – Head of Laboratory Services
– 2008 – 2009
 Chepkoilel University College – Lecturer and program coordinator,
Biochemistry program 2009- 2013
 Moi University, College of Health Science - Senior Lecturer and
Post-graduate Program coordinator, Department of Medical
Biochemistry, SOM – This is my current position

8. My research focus
 Superstition?
 Role of phytochemicals as potential treatment to
cardiometabolic diseases such as Diabetes, Obesity and
Cardiovascular disease.
 Use in vitro, ex vivo and in vivo approaches to investigate plant derived
compounds for;
1. Efficacy
2. Mechanisms of action
3. Toxicity
4. Dose response
 I have recently developed interests in cancer and HIV

9. KENYA STANDS OUT – NEW CANCER CASES

10. 01-Mar-18

11. My Writing Projects at JIAS
Major: To continue writing a book: Upsurge of
Cancer in Kenya: Risk factors, Pathogenesis and
Feasible Preventive Measures
Minor: To write a research grant proposal: Anti cardiometabolic disease and immune-
boosting potential of African Leafy Vegetables among HIV-infected patients on HAART
in western Kenya
01-Mar-18

12. • CANCER: Use power of information
• HIV/AIDS: Use power of Nature -ALVs
WAR against 2 MONSTERS in KENYA

13. March 1, 2018
Upsurge of Cancer in Kenya: Risk factors,
Pathogenesis and Feasible Preventive Measures
The goal is to get it published by INTECH: World’s largest Science, Technology &
Medicine Open Access book publisher
This will be my first book

14. Book Background
 Initially written as a comprehensive review journal article –
Submitted to Critical Reviews in Oncology/Hematology
 Feed back was too long, should consider publishing as a book
 Edited a bit and submitted to Cancer Causes & Control and
once again, same feedback - consider publishing as a book
 Started working on it as a book, then opportunity to come to
JIAS came up
March 1, 2018

15. Global problem but up-surging locally
 Cancer constitutes a major health care burden in the world
today
 Situation is getting worse in resource-poor settings as seen in
many Sub-Saharan African countries and other
underdeveloped parts of the world.
 Being a typical example, Kenya has experienced an upsurge in
the incidence of various types of cancers in the last few
decades.
March 1, 2018

16. What gap does my book seek to fill?
 Most available literature on cancer is either;
 highly academic hence difficult for the common person to understand or
 extremely simplified making it difficult to fully grasp the extent of the
problem and put in place appropriate actions.
 It is this gap that I seek to fill, with a book that is simple
enough for easy readership yet with sufficient details to guide
the public on best practices that could lead to reduction in the
cancer burden in Kenya.
March 1, 2018

17.  During world cancer day, 04 February
2016 I consider playing a role in the fight
against cancer especially in my home
country Kenya
 Had dealt a blow to my family earlier in
2010.
 Lost beloved friend/mother to lung cancer
March 1, 2018
My inspiration

18. Her quick background check
 Typical Kenyan Christian (no smoking, no drinking)
 Lived in rural setting (Nandi district)
 Did farming (crop + animal) and small business ( shop +
maize milling – diesel powered)
 Her kitchen was powered by firewood (very smoky)
 House lighting was by kerosene lamp
March 1, 2018

19. My reading gathered!
 Lung cancers (LC) aka pulmonary carcinoma /carcinoma of
the lung had certain associated risks
 LC is associated with smoking, biomass fuels, coal, and
kerosene burned in open fires, primitive stoves, and lamps
March 1, 2018

20. Her environment!
March 1, 2018
So when did exposure begin? Koroboi
Kishagii

21. And so, unfortunately
 Without her knowledge she was chronically exposed
to smoke and soot! Both of which are KNOWN
carcinogens that have been associated with LC
 For cancer the following are critical:
 Exposure to carcinogens
 Dose – higher increases risks
 Duration of exposure – Longer exposure increases risk
March 1, 2018
I pose the question: Why should I care……. or you care………… or we care?

22. MORGAN TSVANGIRAI - wrote a heart moving letter a month before he died
TITLE: My Sun Has Set
Last day when I shed my earthly body. I will cross over to the spiritual realm. My physical body
had fought so many battles in the past. Cancer was but one battle too many. I gave it a shot. In
fact I gave it plenty. “As the cancer ate my insides I could see the toll on my
family. The despair, the misery and the agony which they tried to
hide”…… ”Cancer puts Patient, Family and Friends though untold misery”
Unfortunately on earth you can only control how you live. No one gets to control how they die. Not even why. Sooner or later our spirits will take to the sky. Eventually we
all fly. I've reflected on my life and I'm proud. I managed to inspire lives. I gave hope to husbands and their wives. It was never a plan or target of mine. I did not do it for
high fives. I wanted to stand for workers' rights. I thought that would be enough but I would be found fighting a bigger battle from 1999. History will judge me but I like to
think I did mighty fine. I made my mistakes. I lived through them and I learned. I was a political blacksmith who tried to forge a new Zimbabwe and you know what they
say. I played with fire and I got burnt. I won some hearts. I won enemies too. Some I earned. There were things I could have done better. There were things I couldn't and
those I don't regret. Some seeds I planted in hearts of my people to blossom and fruit years later. I've been broken hearted, I've broken hearts both alive and now as I
depart. I've been human for the most part. I've had controversy but I have also given reason to celebrate. I've been expected to dangle at the end of a rope only to turn
the gloom into hope. All while living on the international stage under a microscope. History will judge me. Did I fail to change the status quo? I don't think so. But it depends
what those who judge are looking for. I think I did more. I opened eyes. I let the people believe they could stare at their tormentors and say no. I would believe I made them
believe they could refuse bread crumbs and instead demand more. I didn't do everything. But sometimes all people need is a start. A sign. I hope that's what I'm
remembered for. As my sun sets yours rises. Make hay while it shines. Follow your heart, dont waste your single life conforming, forcing your soul to do what it despises.
There's a race to be run. There is work to be done. Do your best. I will see you when you join me on the other side. Morgan Tsvangirai, Late
opposition president of Zimbabwe's MDC
http://www.zambianobserver.com/morgan-tsvangirai-wrote-a-heart-moving-letter-a-month-before-he-died/
March 1, 2018

23. What is cancer?
 a disease caused by uncontrolled division and
spread of abnormal cells in a part of the body.
 an evil or destructive practice or phenomenon that is
hard to contain or eradicate. Good example in my
writing is corruption
March 1, 2018
Corruption is cancer: A cancer that eats away at a citizen’s faith in
democracy, diminishes the instinct for innovation and creativity
– Joe Biden, Former vice president of the USA

24. Salient features of corruption
March 1, 2018
1. Comes in
different forms
2. Powered by
greed
3. Evil
4. Destructive
5. Hard to contain
6. Spreads

25. March 1, 2018
Salient features of cancer
1. Comes in
different forms
2. Powered by
greed
3. Evil
4. Destructive
5. Hard to contain
6. Spreads

26. Cancer is a multi-step process
March 1, 2018
Borrowed from: Chemical Carcinogenesis by James E. Klaunig

27. What’s marvelous about us!
Our bodies successfully fight/
control cancer on a daily
basis.
Sun, food, air, water,
infections etc.
Thanks to our Immune system
(Police – law enforcement!)
March 1, 2018
World’s Mightiest Girl, Mary Marvel, disposing of a hail of bullets in a decidedly
marvelous manner. Go girl!, Cartoons by Bob Oksner, Feb 1975
The story was by uber-fan, and long-time DC editor, E Nelson Bridwell, a master at crafting the
kind of stories that gladdened the heart of the jaded Silver Age reader.
M
a
r
y
M
a
r
v
e
l
E
a
t
s
L
e
a
d
.
!

28. March 1, 2018
• Based mostly on extensive
literature research on these four
areas
• Global cancer risk factors
• Filtered to the Kenyan
ecosystem
• National cancer registry
– KEMRI
• Journal articles
• Other media sources
Use easy language/
pictures/ cartoons/ figures/
simplified tables to pass the
message

29. March 1, 2018
General
Introduction Why cancer is a growing problem in Kenya/ Developing world:
- Poor diagnostic – most cancers diagnosed at stage IV
- Lack of treatment options (too expensive/ inaccessible)
- Poor management (follow up)
- Lack of proper knowledge…e.g. cancer as a disease!
Cancer is
Not witchcraft!

30. The IARC have devised a system that ranks the carcinogenicity of an agent to
humans.
March 1, 2018
Carcinogen: a substance capable of causing cancer in living tissue.
https://www.iarc.fr
We can accurately apportion risks

31. March 1, 2018
Research has shown that genetic or hereditary
forms of most cancers are extremely rare and
that that most cancers can be realistically
prevented or managed by making simple day-
to-day dietary and lifestyle changes!!
Toden, S. and A. Goel, The importance of diets and epigenetics in cancer prevention: a hope and promise for the future?
Altern Ther Health Med, 2014. 20 Suppl 2: p. 6-11.
The corner stone of my book:

32. March 1, 2018
Major risk factors of cancer in Kenya
A. Dietary factors
~ In my manuscript, tabulated in “Table 3”: Selected common dietary
components in Kenya, known carcinogenic substances present and associated
(reported) cancer types
In general:
Towards western diets – Nutrition transition
~ shifts in dietary patterns, usually at the community or
population level (Steyn and Mchiza 2014)
Nutritional Transition and the Emergence of Non Communicable Diseases in Sub-Saharan Africa
– Benard Ng‟eno, MSc Biochemistry student, University of Eldoret

33. March 1, 2018
What‟s bad about
Western diets?

34. March 1, 2018

35. Carcinogenic dietary components common in Kenya
1. High carbohydrate load (Staples) and soft drinks
-Elevates blood glucose, insulin and insulin-like growth factor 1
Influence of Kenyan Staples on Post Prandial Glycemia and levels of Glucagon-Like Peptide-1
(GLP-1) – Rachel Korir, MSc Medical Biochemistry student, Moi University
• Tomor cells - thrive under high glucose
• Glucose, Insulin and growth factors favor prolonged tumor survival
NB: Gluten – Has been associated with intestinal cancer, BUT even then, gluten only
increases risk if a person has celiac disease, or true gluten intolerance.
Ugali Chapati Wali Matoke Beans soft drinks chai

36. 2. Meats
March 1, 2018
HCAs: heterocyclic amines
PAHs: polycyclic aromatic hydrocarbons;
―nyama choma‖ or
Nyam chom
- High-temperature cooking methods generate
compounds that contribute to carcinogenic risk!
- Charred meat1 (HCAs and PAHs)
- e.g. in “nyama choma”
- Highly processed meat1
- Red /organ meat2A
• Kenya staple are usually served with various meats and/
or vegetables.
• Meat is either stewed or roasted
Popular chomas
• Beef
• Goat
• Chicken
MECHANISM OF CARCINOGENESIS
https://www.cancer.org/latest-news/world-health-organization-says-processed-meat-causes-cancer.html

37. March 1, 2018
3. Reused frying oil
Deep fried foods are becoming increasingly common in Kenya with
French fries, wheat products as mandazi and doughnuts, chicken and
fish.
To cut costs: venders recycle the cooking fats/oils used in the deep
frying process over and over
Repeated high temperature heating - carcinogenic substances which
accumulation with every re-use
These includes:
-PAHs (e.g. B[a]P)1
-Acrylamide2A
-Acrolein3
Mandazi
PAHs: polycyclic aromatic hydrocarbons
B[a]P: benzo[a]pyrene;

38.  Purpose: Added to cooking oil
 Such mineral oils are considered to increase
the cooking oil stability allowing deep frying
oils to be reused for longer periods
 Not yet well documented in Kenya
MECHANISM OF CARCINOGENESIS
 Accumulation of PAHs, acrylamide and acrolein
 Contains polychlorinated biphenyls (PCBs)
March 1, 2018
4. Transformer oil - It gets worse
A man electrocuted during an attempt to siphon oil
from a transformer in Dandora, Nairobi on Sunday
night. Photo/ELIZABETH WERE
Sub-acute oral toxicity of transformer mineral oil in rats - Grace Nelima, MSc Biochemistry student, University of Eldoret
What other toxic effects???

39. 5. French fries (chips)
March 1, 2018
Chips, ―Chipo‖
PAHs: polycyclic aromatic hydrocarbons;
Important features include;
• High fat
• Low dietary fibre
• High salt
• Carbohydrate loaded
-PAHs1
-Acrylamide2A
-Acrolein3
• There has been a rapid rise in the number of fast
food outlets most of which will have French Fries
on the menu.
• French fries contain high levels of PAHs,
acrylamide and acrolein all of which are associated
with breast cancer.
• Subway
• KFC
• Domino’s pizza
• Naked Pizza
• Java house
Recent entrants

40. 6. Kerosene (accidental/Intentional
inclusion)
• Kerosene is used as an energy source for
heating and lighting in many parts of the
world: cheap and readily available.
• Colorlessness and lack of odor - mistaken for
water especially by children
• MECHANISM OF CARCINOGENESIS
• Benzene1
• In rat kerosene supplementation
• lead to higher testosterone levels –
• Lead to more aggressive tendencies e.g.
burrowing and fighting
• East African schools belief of it reducing the sex
drive (libido) at the pubertal stage.

41. MECHANISM OF PATHOGENESIS:
 Alcohol (Ethanol1) is metabolized by
the enzyme called alcohol
dehydrogenase (ADH) to
acetaldehyde1.
 Acetaldehyde causes DNA mutations
 Further, acetaldehyde results in the
damage of the antioxidative defense
system (AODS).
 NB: Alcohol is the same whether in
wine, beer or spirits (CH3CH2OH)
March 1, 2018
7. Alcohol consumption
http://www.cancerresearchuk.org/sites/default/files/styles/cruk_wide_re
sp_breakpoint_one/public/alcohol-infographic.jpg?itok=a6ktl-hi
• Many impurities
• Intentionally
adulterated e.g
Kumi kumi
Local brew

42. Illicit brew is a direct killer in Kenya
March 1, 2018
• The most egregious example was in
November 2000, when 140 people in
Nairobi’s Mukuru Kayaba slum died after
drinking Kumi Kumi (―Ten Ten‖ in English),
named because it cost just 10 Kenyan
shillings (R1.50) per serving.
• Another 80 people were left blind.
• Presence of the impurity called Methanol
In 2015: Kenyan overnment banned at least 385 brands of second generation
alcohol and 112 companies as it continues waging war on illicit brews.
CH3CH2OH CH3OH

43.  MECHANISM OF CARCINOGENESIS
1. Salt strongly enhances gastritis
2. Salt also facilitates colonization of H. pylori
 The above are both risk factors for gastric carcinogenesis [65, 87, 99] as
they lead to intestinal metaplasia, dysplasia, early gastric cancer and
eventually advanced gastric cancer [180].
March 1, 2018
8. Salt

44. 9. Antibiotics
• MECHANISM OF CARCINOGENESIS:
• https://www.nature.com/news/scientists-bust-myth-that-our-bodies-have-more-bacteria-than-human-cells-1.19136
Causes Dysbiosis - microbial imbalance on or inside the body.
• Microbiota and host form a complex „super-organism‟
• The microbiome is often termed as the ―forgotten organ‖
• Altered microbiome may promote resistance to cell death — one of the
hallmarks of cancers — and may trigger cancer-promoting inflammation.
• Altered microbiota may release of carcinogenic molecules;
• genotoxins,
• tumour-promoting metabolites.
Agricultural sources (Growth promotion, Disease prevention, Sick animal treatment)
Oncogenic species: S. bovis, H. pylori, B. fragilis, E. faecalis, C. septicum, Fusobacterium spp. and E. coli.

45. March 1, 2018
10. Aflatoxins1
Due to poor storage of
cereals (maize and wheat)
Fungal toxin
• Most of the research was in the 70’s and 80’s [109].
• Known risk factor for the development of Hepatocellular carcinoma (HCC)
• MECHANISM CARCINOGENESIS:
• Aflatoxin causes DNA modification (mutation)
• Aflatoxin contamination could occur indirectly through consumption of animal
products such as milk, blood and meat [63].
• In Kenya maize, wheat, rice are dietary staples and major sources of animal
feed.
• Complicated by climate change (plant-harvest cycles)

46. March 1, 2018
11. Fermented /sour milk
• This is prepared through a fermentation process which yields alcohol
and acetaldehyde
• The protocol for the production of mursik includes the addition of soot
from burnt wood for purposes of flavor and as a preservative [118].
• CARCINOGENICITY:
-Ethanol1
-Acetaldehyde1
-Soot1 (in mursik)
-Cholesterol3
Mursik

47. 12. Roasted coffee
March 1, 2018
• Kenyans are predominant tea drinkers
• Entry of Art Caffe and Java House signs that drinking is on the increase
• Roasting transforms the chemical and physical properties of green coffee beans into
roasted coffee products.
• The roasting process produces the characteristic flavor and taste of coffee.
MECHANISM OF CARCINOGENESIS:
-Acrylamide2A: is created when coffee beans are roasted.
Coffee may soon come with a cancer warning in California state
Java, Seven eleven, Starbucks…… asked sign agreement
13 have agreed to do so!
https://edition.cnn.com/2018/01/31/health/cancer-coffee-warning/index.html

48. March 1, 2018
Major risk factors of cancer in Kenya
B. Environmental factors:
Factor Description Carcinogens Associated
cancer(s)
Domestic use of
carbon-based fuels
wood, charcoal,
dung, kerosene and
diesel
benzo[a]pyrene
Formaldehyde
benzene and PAHs
Lung, head and neck
cancers and
esophageal
Agrochemicals
exposure
pesticides and
herbicides,
antibiotics
non-Hodgkin
lymphoma and
colorectal carcinoma
Tobacco use
(smoking and
snuff)
PAHs and
nitrosamines
LUNG, oral,
esophageal and
breast cancer

49. March 1, 2018
Factor Description Carcinogens Associated
cancer(s)
“Jua kali”
sector and
others
welders, painters, mechanics,
carpenters and “open air”
vendors, pastoralists, crop
tenders, construction workers and
fishermen
Excessive exposure to
solar UV radiation ,
automobile exhausts
Skin cancer
Asbestos Roofing, motor vehicle clutch or
brake pads, sewer pipes, ceiling
and floor tiles, paper and cement
products, textiles, and also in
some types of paints
Their biopersistance
leads to generation of
reactive oxygen
species
lung cancer,
and
mesothelioma
Kenyan old residential estates such as Nairobi’s Bahati, Kimathi and Ofafa Jericho continue to
collect rainwater for domestic use from asbestos rooftops oblivious to the potential risks
B. Environmental factors:

50. Environmental carcinogenesis (Kenya)
Asbestos roof Jua kali artisans Snuff container
March 1, 2018
no sun block
no sun glasses
Filter or no
filter don’t
matter
Aging - carcinogenic
potential is
exacerbated

51. Poor waste management and disposal
 E.g. In Nairobi Kenya - the emergence of one of Africa’s largest
open dumpsite, the Nairobi’s Dandora dump site
 Soil analysis: lead (Pb), mercury (Hg), cadmium (Cd), copper
(Cu), zinc (Zn), arsenic (As), silver (Ag), iron (Fe), and chromium
(Cr)
 Human exposure - derives from drinking water, air and food
 Arsenic (As) is a group 1 carcinogen while lead is group 2A
 Decomposition leads - volatile organic compounds (VOCs) e.g.
formaldehyde1[164].
March 1, 2018
B. Environmental factors:

52. March 1, 2018
Kachok dumpsite hill in Kisumu. [Photo by Denish
Ochieng/ Standard]
Dandora dumpsite, Nairobi: https://www.businessdailyafrica.com
Butadiene, and heavy metals (Nickel (Ni), Cr, and Cd) have also been indicated as possible human
carcinogens

53.  Mostly viruses however, bacteria and human parasites also play
a role
 ~15% of all human cancers worldwide
 Both DNA and RNA viruses capable of causing cancer in humans.
 DNA viruses: Human papilloma virus HPV), hepatitis B virus (HBV),
and human herpes virus-8 (HHV-8), Epstein-Barr virus (EBV)
 RNA viruses: Human Immunodeficiency virus (HIV), Human T
lymphotrophic virus (HTLV) type 1 and hepatitis C viruses (HCV)
March 1, 2018
Major risk factors of cancer in Kenya
C. Infectious agents (~ 18% of the global cancer burden)

54. On viruses and cancer!
 Virises my cause cancer by activating proto oncogens (viral and human).
 Proto oncogenes: Normal genes affecting normal cell growth and
proliferation ( Cell growth, division, halt differentiation and halt cell
death)
 GOOD NEWS!!: The path from viral infection to tumorgenesis is slow and
inefficient; only a minority of infected individuals progress to cancer,
usually years or even decades after primary infection.
March 1, 2018
Tumor suppressor genes: Slow cell growth and division, instruct defective cells to
die (apoptosis), and repairing mutations

55. March 1, 2018
Major risk factors of cancer in Kenya
C. Infectious agents
Infectious agent Description Pathogenesis Associated
cancers
Humanpapilloma
virus (HPV16 and
HPV18 )
Approximately 5% of all
human cancers, which
corresponds to one-third
of all virus-induced
tumors
- Viral induced
DNA damage
- Immunosupression
cervical cancers
(50%)
Human herpes
virus-8 (HHV-8)
Epstein-Barr virus
(EBV)
Implicated in many CA
processes i.e. tumor-
promotion inflammation,
immune evasion, and
immunosuppression
transcriptional
repression of the
tumor suppressor
gene PDZ-LIM
Kaposi's sarcoma
- skin
- lymph
nodes
- other
organs

56. March 1, 2018
C. Infectious agents
Infectious
agent
Description Pathogenesis Associated
cancers
Hepatitis
virus
• HBV and/or HBC are
the major risk factors
for liver cancer
• Kenya belongs to the
African Region-E
HBV - chronic, intermittently
active inflammation that
provides "fertile field" for
“mutation, selection, and
adaptation”
Hepatocellular
carcinoma -
liver cancer
Helicobact
er pylori
well-recognized gastric
carcinogen
GC in only 1-3% of H.
pylori
Causes gastritis which
progress to intestinal
metaplasia, dysplasia, early
gastric cancer (GC), GC
gastric cancer
African Region-E characterized by high mortality and hyperendemicity of HBV

57. Infectious agents and cancer
March 1, 2018
Hepatitis B virus

58. March 1, 2018
C. Infectious agents
Parasitic infections
Infectious
agent
Description Pathogenesis Associated
cancers
Untreated
parasitic
infections
• E.g. Schistosomiasis
or bilharzias
• one of the so called
“neglected tropical
diseases”
serious and irreversible lesions in
the urogenital tract - may
eventually lead to squamous cell
carcinoma of the bladder
Bladder
cancer

59.  Many studies have linked the emergence of HIV/AIDs to an
upsurge in various kinds of cancers
 Kenya is among world leaders with large numbers of people
living with AIDS (PLWA)
 Expectable that AIDS-related diseases, complications and
infections would occur at a similar rating.
March 1, 2018
C. Infectious agents: HIV Virus
HIV/AIDS related immunosuppression and the use of HAART

60. Important questions to respond to: NCI
 Do people infected with human immunodeficiency virus (HIV) have an
increased risk of cancer?
 Why might people infected with HIV have a higher risk of some types of
cancer?
 Has the introduction of antiretroviral therapy changed the cancer risk of
people infected with HIV?
 What can people infected with HIV do to reduce their risk of cancer or to
find cancer early?
NCI: National cancer institute, Part of NIH with a team 3500 strong!
March 1, 2018

61. A. AIDS-defining cancers
 Also referred to as "AIDS-defining malignancies"
 Three main types:
 Kaposi sarcoma
 aggressive B-cell non-Hodgkin lymphoma and
 cervical cancer
 A diagnosis of any of these cancers in someone infected with
HIV confirms a diagnosis of AIDS
March 1, 2018

62. Mechanism of HIV tumorigenesis
I. HIV virus induces immune tolerance (immunosuppression)
This impairs tumor immune surveillance allowing survival of aberrant
cells [15] to form tumors.
2. Tumors by themselves also induce immunotolerance [131] – like police
bribery
 Immune tolerance confers an elevated causative risk of developing
several different types of solid tumors [130].
 So among PLWA once cancer initiation has occurred, the speed of
progression to metastatic cancer is greatly enhanced.
March 1, 2018
Two key findings form models and cancer patients

63. Cancer type Likely populations most at risk or with
higher incidence
Selected salient features
AIDS-defining HIV associated
neoplasms
Kaposi’s sarcoma (KS)
Cervical cancer (CVC)
Non-Hodgkin’s lymphoma
(NHL)
Burkitt’s lymphoma (BL)
 Endemic (EBL)
 Sporadic (SBL)
 Immunodeficiency-
associated (IBL)
Ocular surface squamous
neoplasia (OSSN)
- HIV/AIDS patients
- KS is high in both gender but higher in males
- Female HIV/AIDS patients are at a higher
risk for CVC than general female population
- Children face higher risk for EBL, while IBL
occurs more in immune deficient individuals
- BL is higher among Nyanza, Western and
Coastal communities
- NHL cases are high in patients with HBV, HCV
and Helicobacter pylori infections
- NHL is higher among chemically exposed
subjects (phenoxy herbicides)
- NHL is higher in men than women
- NHL is also higher among older people
- OSSN is higher among persons exposed to
excess UV radiation, and vitamin A
deficiency [15]
- KS is ranked top in this category
[40]
- KS and CVC are associated with
HPV and HIV which makes ethnic
groups with lower levels of/or no
male circumcision more prone [29,
46]
- OSSN may be higher in Kenyan
women due to their higher HIV
and HPV prevalence [15]
- Nyanza, Western and Coastal
regions are associated with high
prevalence of HIV/AIDS [28] and
or high malaria incidence rates
[47]

64. HAART and ADCs
 HAART use has been associated with a positive impact on the
incidence of AIDS-defining infectious and malignant diseases
including KS and NHL [19].
 Screening the populations for HIV and rapid initiation of
HAART for positive cases may therefore help to reduce the
incidence of AIDS-defining cancers.
March 1, 2018

65. B. Non-AIDS-defining HIV associated neoplasms
 The introduction and widespread use of HAART has prolonged
the lives of PLWA
 However, it has also prolonged duration of exposure to
environmental and lifestyle cancer risk factors, and co-infection
with oncogenic viruses.
 In the light of their immunocompromised status, the prolonged
exposure contributes to the development of NADCs
March 1, 2018
Questions: 1. How can we boost immunity at the backdrop of HAART use?
2. How can we prevent/ alleviate the side effects of HAART use?

66. In attempt to provide answers I spent 1st 2weeks at JIAS – Grant
“Anti cardiometabolic disease and immune-boosting potential of
African Leafy Vegetables among HIV-infected patients on HAART in
western Kenya”
 Multidisciplinary (Medicinal chemistry, Medical Biochemistry,
Molecular biology and Immunology)
 We will work with both HIV patients from out AMPATH program and
cell cultures (liver cells – HepG2)
 Submitted to the National Research Fund ($ 200,000)
 To find out in April
March 1, 2018

67. March 1, 2018
Cancer type Likely populations most at risk
or with higher incidence
Selected salient features
Non-AIDS-defining HIV
associated neoplasms
-Skin cancer (SC)
-Anal cancer (AC)
-Hodgkin disease
-Lung cancers (LC)
aka pulmonary
carcinoma /carcinoma of
the lung
- HIV/AIDS patients on
HAART
- Individuals with lighter
skin/white are at higher
risk for SC
- Smokers, rural household
workers/ women are at an
increased risk for LC
- Squamous cell carcinoma of the conjunctiva
(SCCC), a type of SC is ranked top in this
category [40]
- There is strong evidence for increased risk
of developing AC during the HAART era
[48]
- LC is associated with smoking, biomass fuels,
coal, and kerosene burned in open fires,
primitive stoves, and lamps [13]
- There is difficultly in early diagnosis of SC
among black people [49]
- SC correlates with the level of cutaneous
pigmentation [50]

68. D. Genetic predisposition
 Approximately 2% to 5% of the majorities of cancers are driven by
germline mutations – can be passed on
 Genetic predisposition is not necessarily sufficient and will require the
interplay between the genome and the epigenome, which together interact
with environmental factors, including nutrition for cancer to occur [64].
 The epigenome is made up of chemical compounds and proteins that can attach to
DNA and direct such actions as turning genes on or off, controlling the production of
proteins in particular cells.
 When epigenomic compounds attach to DNA and modify its function, they are said
to have "marked" the genome.
March 1, 2018
Major risk factors of cancer in Kenya

69. Few studies in Kenya appear to link lineage to cancer
March 1, 2018
Ethnic community Known confounders Cancer type
Luo, Luhya and
Coastal ethnicities
? Burkitt’s lymphoma
Kalenjin Mursik (sour milk) Esophageal cancer
Asians and whites Less melanin cutaneous melanoma (CM)
Blacks ? Prostate cancer (PC)
Examples:

70.  The process of carcinogenesis is complicated and in most cases requires
several steps of cellular transformation resulting from various molecular
signals brought about by interactions between carcinogens and the cellular
genome……… the longer the period the more the effects
 A GOOD EXAMPLE: KNH study on the incidence of prostate cancer, the
leading cancer type among Kenyan men showed than 85% of the patients
were aged over 61yrs with a peak incidence in the 66-70yrs (mean 67)
[174].
 With increasing life expectancy due to better health care and improved
nutrition, more and more Kenyan men live to reach this age bracket raising
the number of cases.
March 1, 2018
E. Advancing Age
Major risk factors of cancer in Kenya

71.  IMMUNODEPRESSION: Shows less efficient immune cells production,
autoimmunity and decreased responses to infections, tumours and
vaccinations
 Data from Nairobi Cancer Registry: There is a steady increase in incidence
in all the cancers with age in Kenya, and is more marked among men than
women [32]
 Among Kenyan women observed difference may be attributed to hormonal
changes that occur post-menopause with hormonal alterations occurring at
this stage among women appearing to be cancer protective.
 Postmenopausal hormones (PMH) use increases incidence of breast cancer,
an effect made worse by simultaneous PMH use and alcohol drinking[173].
March 1, 2018
Advancing age ……….

72.  Increase in white collar jobs and motorized transport
 Consistently expending fewer calories than are consumed leads to
obesity, which scientists have convincingly linked to increased risks of
13 different cancers
 Please visit (http://www.nejm.org/doi/10.1056/NEJMsr1606602)
March 1, 2018
F. Physical inactivity
Major risk factors of cancer in Kenya

73. What is recommended?
 Adults at least 150 minutes of moderate-intensity
aerobic physical activity or
 75 minutes (1 hour and 15 minutes) of vigorous-
intensity aerobic physical activity, or
 An equivalent combination of moderate- and
vigorous-intensity activity, every week.
March 1, 2018

74. Boda boda “convenience” in Kenya
 Highly used due to:
 Their ability to maneuver
through bad roads
(including foot paths)
 Beat traffic
 Very low fares
March 1, 2018
http://www.informereastafrica.com/sites/default/files/styles/large/public/fiel
d/image/Getty%20impages.jpg?itok=iwLIBa2u
Story “Boda Boda business becoming a death trap in Kenya”

75. What else is bad about automobiles in Kenya?
1. Automobiles have added directly to
the increased mortality rate in
Kenya through traffic accidents
2. Contributed to automobile-related
environmental pollution with
emission of potentially carcinogenic
substances such as benzene [16, 18]
March 1, 2018
https://i.pinimg.com/736x/fb/90/01/fb90018da3e53d74d79b936e0c74907f.jpg

76. Pattern of distribution
March 1, 2018
Feasible Cancer Preventive Measures in Kenya
and

77. Children (≤
15yrs)
i. Lymphomas (Mostly Burkitt’s and
to a less extent non-
Hodgkin’s/Hodgkin’s)
ii. Leukemia (lymphocytic)
iii. Wilms tumor (nephroblastoma)
Women i. Breast cancer
ii. Cervical cancer
iii. Esophageal cancer
Men i. Prostate cancer
ii. Esophageal cancer
iii. Kaposi’s sarcoma
Young
people (≤
30yrs)
Males
i. Esophageal cancer
ii. Colorectal cancer
iii. Stomach cancer
Females
i. Breast cancer
ii. Cervical cancer
iii. Colorectal cancer
Older people
(≥ 65yrs)
Males
i. Prostate cancer
ii. Esophageal cancer
iii. Colorectal cancer
Females
i. Cervical cancer
ii. Breast cancer
iii. Stomach cancer
HIV/AIDS
patients
AIDS-defining cancers
i. Kaposi’s sarcoma
ii. Cervical cancer
iii. Non-Hodgkin’s lymphoma
iv. Burkitt’s lymphoma
v. Ocular surface squamous neoplasia
On HAART treatment
i. Skin cancer
ii. Anal cancer
iii. Hodgkin disease
iv. Lung cancers
v. Hepatocellular carcinoma
Demographic patterns of the various cancer types in Kenya

78. Cancer type Feasible preventive measures
Breast (BC) • Timely screening and awareness campaigns
• Avoidance/reduction of alcohol intake [8]
• Cessation of smoking
• Avoidance of postmenopausal hormones (PMH) use [9]
• Intake of vitamin rich diets
• Intake of low dietary fat and cholesterol content
• Intake of high dietary fiber content
• Reduced intake/avoidance of french fries (chips)
• Regular physical exercise
Leukemia (LK) • Reduction/ avoidance of kerosene (benzene content) fuel
• Avoidance of living close to heavy-traffic roads
• (benzene) [21]
• Adequate breast feeding
• HIV screening, infection control and treatment
• Proper waste management and disposal
https://www.webmd.com/menopause/news/20171212/postmenopausal-women-should-avoid-hrt#1

79. March 1, 2018
Cancer type Feasible preventive measures
Cervical (CVC)  Intensifying CVC awareness campaigns and screening
 Promotion of HIV voluntary testing and counseling
 Increased access to and early initiation of ART among HIV positive cases
 HIV screening, infection prevention and treatment
 Screening HIV patients for CVC
 HPV infection prevention especially through use of efficient prophylactic
vaccine
 Promotion of male circumcision
Colorectal (CC)  Proper industrial and agricultural waste disposal and management
 Avoidance/reduction of alcohol intake
 Avoidance/reduction of intake of ‘western diets”
 Avoidance of mursik intake
 Screening of close relatives of victims of CC

80. March 1, 2018
Cancer type Feasible preventive measures
Esophageal (EC) • Avoidance of alcohol intake
• Avoidance of domestic biomass and coal-based fuel use (wood, dung
and coal) [17]
• Screening of close relatives of victims
• Increased intake of fruits and vegetables
• Cessation of smoking
• Avoidance of very hot beverages (tea, coffee etc)
• Avoidance of very salty foods
• Avoidance of deep fried foods [18]
• Avoidance of intake of sour milk (mursik)
Prostate (PC) • Avoidance of deep fried foods and re-use of cooking oil
• Regular PC screening
• Screening of close relatives of victims
• Avoidance of western diet and foods rich in cholesterol
• Eating high-fruit diets [36]

81. Pending work!
 Rewriting the mechanisms of pathogenesis and a few other sections
in simple language
 Simplifying information currently in large tables to be reader
friendly
 Photos and permissions where required
 Simple figures for data representation
 Including strategies for early detection of various cancer type
 Think about how to reach the rural communities and illiterate
members of the society
March 1, 2018

82. After JIAS project in mind……
 To write a Medical Biochemistry Text book that
incorporates poetry, cartoons, short stories and...
 Breaking the ice, for
March 1, 2018

83. Looking forward to a brighter future, better equipped for research!
01-Mar-18
Arrival of equipment from Seeding labs, Boston, USA Ruto, Rachel, Fosia, Dorcus and Dr. Maiyoh
1st graduate student, MSc Med. Biochemistry

84. Aknowledgements
 Prof. Peter Vale – Director JIAS
 Ms. Reshmi – Academic manager JIAS
 Mr. Ronald – Accommodation manager JIAS
 Ms. Emilia
 All my colleagues (fellow fellows)
 Moi University management
01-Mar-18
THANK YOU ALL

85. March 1, 2018