MASTER’S IN ENVIRONMENTAL HEALTH AND SAFETY

FACULTY OF HEALTH SCIENCES

UNIVERSITI TEKNOLOGI MARA

ENV 703 ENVIRONMENTAL

EPIDEMIOLOGY
ASSIGNMENT 1
GENE x Environment Interaction for
Breast Cancer

LECTURER: DR. ALIA AZMI

NAME ID MATRICS

HIDAYAH BINTI ABDULLAH 2021835834

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Definition of gene x environment
Gene environment interaction is defined as “a different effect of an environmental exposure
on disease risk in persons with different genotypes or alternatively, a different effect of a
genotype on disease risk in person with different environmental exposures”. Modern
technology with molecular biology led to various changes in both genetic and environmental
factors which contribute to susceptibility and risk of disease.

Environmental risk
factor (high risk
genotype)

Can be behaviour Can be physical factors

pattern such as late such as radiation,
age of first pregnancy temperature.
of life event like loss
job

Can be biological Can be chemical factors such as

factors such as virus polycyclic aromatic hydrocarbons

Illustrious of gene – environment interaction to breast cancer

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 Simple infographic to explain two different genotypes respond to environment in
different ways

Breast cancer introduction

Breast cancer is a disease which certain cell in breast become abnormal and multiple
uncontrollably to form a tumour. Although breast cancer is commonly found in women, this
form of cancer also can be found in men. Breast cancers begin in cells lining the milk ducts
or in the glands that product milk. In early stage, breast cancer usually does not cause pain
and may not exhibit any noticeable symptoms. As the cancer progress, sign and symptoms
can be include lump or thickening in or near the breast, change in size or shape of breast,
nipple discharge, tenderness or retraction and others.
In some cases, cancerous cells can be invaded surrounding breast tissue which known as
invasive breast cancer. Sometimes tumour can be spread to other parts of body and most
often appear in bone, liver and lungs. Tumours that begin from one side and then spread to
other areas of body are called metastatic cancer.

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 Breast cancer symptoms

Ductal carcinoma in situ (DCIS). Abnormal cells are found in the lining of a breast
duct

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 Breast cancer stage 1 – 4

Heterogeneity in breast cancer

Breast cancer is one of the few tumours which successfully been used for the design of
individual therapies. Major breast tumours are classified into luminal, human and epidermal
growth factor receptor 2+ (HER2+), and basal. Each subtype has different risk factors for
incident, response to treatment, risk of disease progression and preferential organ sites of
metastases. Luminal tumors are positive for estrogen and progesterone receptors, and the
majority respond well to hormonal interventions, whereas HER2 + tumors have amplification
and overexpression of the ERBB2 oncogene and can be effectively controlled with a diverse
array of anti-HER2 therapies. Basal-like tumors in general lack hormone receptors and
HER2; thus, the majority of these tumors are also called triple-negative breast cancer
(TNBC). Currently there is no molecular-based targeted therapy for TNBC, and unfortunately
only approximately 20% of these tumors respond well to standard chemotherapy. Thus,
developing improved treatments for TNBC is one of the highest priorities of current breast
cancer research. Numerous agents are in various phases of clinical development, including
several different poly (ADP-ribose) polymerase inhibitors, JAK kinase, and EGFR inhibitors
as well as “revived” classical chemotherapeutic agents such as platinum salts. However, so
far none of these shows promise for treating all TNBCs, a finding that perhaps is not
surprising given that several recent studies have described that even this relatively small
class of breast tumors can be further divided into five or six subclasses, each with its own
molecular features and unique sensitivity to therapeutic agents.

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 Different types of intratumor reaction for treatment

Pathogenesis of breast cancer

Pathogenesis is the process by which a disease or disorder develops. It can include factors
which contribute not only to the onset of the disease or disorder, but also to its progression
and maintenance. The word comes from Greek πάθος pathos 'suffering, disease' and
γένεσις genesis 'creation'.

Age
Probablity
develop breast
cancer incease
with age

Genes Personal
History
Inherent Factors that
breast affect breast Initial
cancer genes cancer diagnosis
from parent of DCIS,
stage IIB

Family
history
Mother/relat
ive with
history

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 Overview of risk factors associated with breast cancer
The diagram summarizes the unavoidable (inherited) and modifiable risk factors that can
ultimately lead to tumorigenesis. Genes/pathways/risk factors are shown in red; inherited or
unmodifiable factors are shown in green; modifiable variables are shown in blue; life events
are represented by gray boxes; increased/positive effects are denoted by solid arrows; and
reduced/negative effects are denoted by dashed arrows. AIs, aromatase inhibitors; ATM,
ataxia telangiectasia mutated; BRCA1 and BRCA2 (genes in which deleterious germline
mutations increase the risk of cancer); CAFs, cancer-associated fibroblasts; CHEK2, CHK2,
checkpoint homolog; HRT, hormone replacement therapy; SERMs, selective estrogen
receptor modulators.”

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Evidence based complex system model of postmenopausal breast cancer causation. This
model displays multiple factors associated with postmenopausal breast cancer causation in
four broad domains and shows their interconnections across levels(genes to society) by
arrows that indicate variations in the strength of the associations and the quality of the data.

Early menarche. Delay in menarche by 2 years associate with risk

reduction of 10%

Breast feeding. Will protect and delay return of regular ovulatory

cycles and decrease endogenous sex hormone levels

Age of menaopause. Later onset of menaopause confers 3%

increase in risk

Testoterone. High endogenous sex hormone levels increase the risk

of breast cancer both in premenopausal and postmenopausal

Endogenous hormone exposure and reproductive factors

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Obesity Physical activity Radiation
Risk increase as BMI Consistent physical Radiation exposure
increases activity reduce the from various source
risk of breast cancer such medical
in a dose equipment increse
dependent manner risk of breast cancer
Alcohol Comsuption
Binge drinking, but
not frequency of
drinking, was
associated with
breast cancer risk
after controlling for
cumulative alcohol
intake.

Environment lifestyle factor could increase risk of gene breast cancer

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Prevention of breast cancer

1. Get to and stay at a healthy weight: Both increased body weight and weight gain
as an adult are linked with a higher risk of breast cancer after menopause. The
American Cancer Society recommends you stay at a healthy weight throughout your
life and avoid excess weight gain by balancing your food intake with physical activity.

2. Be physically active: Many studies have shown that moderate to vigorous physical

activity is linked with lower breast cancer risk, so it’s important to get regular physical
activity. The American Cancer Society recommends that adults get at least 150 to
300 minutes of moderate intensity or 75 to 150 minutes of vigorous intensity activity
each week (or a combination of these), preferably spread throughout the week.
Getting to or exceeding the upper limit of 300 minutes is ideal.

3. Avoid or limit alcohol: Alcohol increases risk of breast cancer. Even low levels of

alcohol intake have been linked with an increase in risk. It is best not to drink alcohol.
For women who do drink, they should have no more than 1 alcoholic drink a day. A
drink is 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80-proof distilled spirits
(hard liquor)

4. Close observation to look for early signs of breast cancer. More frequent doctor
visits (such as every 6 to 12 months) for breast exams and ongoing risk assessment.

5. Genetic counselling and testing. If there are reasons to think you might have
inherited a gene change that increases your risk of breast cancer (such having as a
strong family history of breast cancer, or a family member with a known gene
mutation), you might want to talk to your doctor about genetic counselling to see if
you should be tested. 

6. Medicines such as tamoxifen and raloxifene block the action of estrogenic in breast

tissue. Tamoxifen might be an option even if you haven’t gone through menopause,
while raloxifene is only used for women who have gone through menopause. Other
drugs, called aromatase inhibitors, might also be an option for women past
menopause. All these medicines can also have side effects, so it’s important to
understand the possible benefits and risks of taking one of them.

7. Prevention surgery of high-risk women. For the small fraction of women who have
a very high risk for breast cancer, such as from a BRCA gene mutation, surgery to
remove the breasts (prophylactic mastectomy) may be an option. Another option
might be to remove the ovaries, which are the main source of estrogen in the body.
While surgery can lower the risk of breast cancer, it can’t eliminate it completely, and
it can have its own side effects.

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 Treatment of breast cancer

If someone has been diagnosis with breast cancer, there can be various of treatment to think
and choose from. Each of the treatment have their own advantages and disadvantages to
think and decide.
1. Local treatment. Some treatments are local, meaning they treat the tumour without
affecting the rest of the body. Most women with breast cancer will have some type of
surgery to remove the tumour. Depending on the type of breast cancer and how
advanced it is, you might need other types of treatment as well, either before or after
surgery, or sometimes both.
2. Systematic treatment. Drugs used to treat breast cancer consider systemic
therapies because they can reach cancer cell almost anywhere in the body. They can
give by mouth or put directly in the bloodstream. Depending on the type of breast
cancer, different types of treatment might be used including chemotherapy, hormone
therapy, target drug therapy.
3. Common treatment approaches. Typically, treatment plans are based on the type
of breast cancer, its stage, and any special situations. Your treatment plan will
depend on other factors as well, including your overall health and personal
preferences. Example like treatment by stage, triple negative treatment, and
inflammatory breast cancer treatment.

Breast cancer treatment

References

1. https://www.allbrandproduct.com/blog/breast-cancer-treatment-in-delhi/
2. https://www.cancer.org/cancer/breast-cancer/treatment.html
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127601/https://www.ncbi.nlm.nih.gov
/pmc/articles/PMC4127601/

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4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195489/
5. https://www.mayoclinic.org/diseases-conditions/breast-cancer/symptoms-causes/syc-
20352470

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