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Breast cancer
1. UNIVERSITY OF GONDAR
COLLEGE OF MEDICINE AND HEALTH SCIENCES
SCHOOL OF BIOMEDICAL AND LABORATORY SCIENCE
TITLE: A Review on Genetic and Environmental Factors for Breast Cancer
NAME OF THE STUDENT: ALEMAYEHU ABATE
NAME OF ADVISORS: MR.WUBET BIRHAN,
MR. YITAYAL SHIFERAW,
MR. BELAY ANAGAW
NOV, 2011
GONDAR, ETHIOPIA
2. OUT LINE
• Introduction
• Background
• Objective
• Global Breast Cancer Burden
• Breast cancer in Africa
• Breast cancer in Ethiopia
• Genetic factors for breast cancers
• Environmental risk factors
• Prevention of breast cancer
• Conclusion
• Recommendations
• References.
3. INTRODUCTION
Breast cancer is a malignant tumor that starts in the cells of the
breast.
occurs almost entirely in women, but men can get it, too
is a major health burden worldwide.
most common cause of cancer in both high-resource and low-
resource settings
4. INT… CONT….
Each year, breast cancer is newly diagnosed in more than 1
million women worldwide and more than 400,000 women die
from it .
growing throughout the world, but especially in developing
regions, where the incidence has increased as much as 5% per
year
hoped that identification of genetic and environmental factors that
contribute to the development of breast cancer will enhance
prevention efforts
5. INT… CONT….
The mortality: incidence ratio is much higher in developing
countries than in developed countries.
Only half of global breast cancers are diagnosed in the
developing world, but they account for three-fourths of total
deaths from the disease.
Breast cancer is a complex, multifactorial disease where there is
a strong interplay between genetic and environmental factors.
6. Objective
The objective of this paper is to compile the current literature
about the genetic and environmental factors for breast cancer.
7. Global Breast Cancer Burden
Breast cancer is the most common type of cancer and the most
common cause of cancer-related mortality among women
worldwide.
there are large variations in the incidence, mortality, and survival
between different countries and regions and within specific
regions
Breast cancer is a common disease in Western societies, with a
lifetime prevalence of 1 in 12 in the United Kingdom and 1 in
8 in the USA (12).
8. Global … cont….
Breast cancer accounts for one-third of cancer diagnoses and 15%
of cancer deaths in U.S. women. Its 192,000 cases and 40,000
deaths
Annual mortality rates ranged from 27/100,000 women in
northern Europe to 4/100,000 women in Asia.
Incidence data are less complete, low in Asia, intermediate in
South America and Eastern Europe, and high in North America
and Western Europe.
9. Breast cancer in Africa
Although breast cancer is the most common neoplasm among
women in developing countries, if Africa is taken as a whole it
ranks second most frequent to cervical cancer (15).
However, it is the most common malignancy in North Africa and
in urban settings within the sub-Saharan region such as
Abidjan (Côte d’Ivoire)
10. Africa … cont….
breast cancer incidence rates will rise. Unless medical care and
screening practices are dramatically improved.
Several protective factors for breast cancer are generally
prevalent among African women, including late
menarche, early age at birth of first child, high parity
(ie, number of children borne per woman, often with
prolonged lactation), low frequency of HRT, and a physically
active lifestyle
11. Africa … cont….
. According to GLOBOCAN 2002 figures, the age-standardized
(world) incidence of breast cancer was
19.5, 23.2, 33.4, 27.8, and 16.5 per 100,000 populations in
East, North, South, West, and Central Africa, respectively .
The lowest reported incidence of breast cancer was in
Mozambique, East Africa (3.9 per 100,000), and the highest
was in the Republic of South Africa (35 per 100,000).
12. Africa … cont….
the incidence of breast cancer among white women living in
South Africa is much higher than among black women (70.2
vs. 11.3 per 100,000, respectively.
mortality rates per 100,000 populations for breast cancer in
Africa in 2002 ranged from 2.8 in Mozambique to 25 in
Botswana. Overall, the estimated rates were 14.1, 16.7, 16.3,
19.6, and 12.1 per 100,000 populations in East, North, South,
West, and Central Africa, respectively.
13. Breast cancer in Ethiopia
Breast cancer is the second most often occurring cancer (cervical
cancer is first) among women in Ethiopia. It is estimated that
around 10,000 Ethiopian women and men have breast cancer .
Both females and males had similar clinical characteristics, except
that, the males were older by 10 years.
females in this series developed breast cancer at a younger age
(72% were premenopausal) and 76% had advanced disease .
14. 2. Genetic and Environmental Factors
2.1 Genetic factors for breast cancers
2.1.1 BRCA1 and BRCA2 genes
About 5% to 10% of breast cancer cases are thought to be
hereditary, resulting directly from gene defects (called
mutations) inherited from a parent.
The most common cause of hereditary breast cancer is an
inherited mutation in the BRCA1 and BRCA2 genes.
These cancers tend to occur in younger women and more
often affect both breasts than cancers in women who are
not born with one of these gene mutations.
15. BRCA… cont….
Germ line mutations in BRCA1 have been identified in 15–20%
of women with a family history of breast cancer and 60–80%
of women with a family history of both breasts.
BRCA1 mutations are found in excess in women with multiple
primary cancers of any type who have both a personal and
family history of breast cancer (30). BRCA1 is a large
gene, with 22 exons encoding a 220-kilodalton nuclear protein
with a zinc-binding RING domain at the amino terminus.
16. BRCA… cont….
BRCA1 binds to BRCA2, p53, RAD51 and many other proteins
involved in cell cycling and DNA-damage response .
The lifetime breast cancer risk for carriers of BRCA2 mutations
also is estimated to be 60–85%.
men with germline mutations in BRCA2 have an estimated 6%
lifetime risk of breast cancer
17. 2.1.2 Ataxia-telangiectasia (AT)
not frequent causes of inherited breast cancer.
The ATM gene normally helps repair damaged DNA. Inheriting 2
abnormal copies of this gene causes the disease ataxia-
telangiectasia. Inheriting one mutated copy of this gene has
been linked to a high rate of breast cancer in some families.
AT carriers (heterozygotes) may have an increased risk for
developing breast cancer.
breast cancer is almost eight times higher in mothers of AT
patients than in the general population .
18. 2.1.3 Tumor Suppressor P53.
be a rare cause of breast cancer.
Inherited mutations of the p53 tumor suppressor gene cause the
Li-Fraumeni syndrome
People with this syndrome have an increased risk of developing
breast cancer.
In women with germline p53 mutations who survive childhood
cancers, it is estimated that 50% will have developed breast
cancer by the age of 50 years.
19. 2.1.4 PTEN gene
normally helps regulate cell growth.
Inherited mutations in this gene cause Cowden syndrome, a rare
disorder in which people are at increased risk for both benign
and malignant breast tumors.
increased incidence of breast cancer among female patients with
Cowden syndrome
20. 2.1.5 STK11 gene
Defects in STK11 gene can lead to Peutz-Jeghers syndrome.
People affected with this disorder develop an increased risk of
breast cancer.
very low prevalence of mutations in the population
21. 2.2. Environmental risk factors
The strongest determinants of breast cancer risk are female
gender, age, and country of birth.
The conventional risk factors of breast cancer are related to
reproductive life (early age at menarche, nulliparity, late age at
the first full-term pregnancy, late age at lactation, short
lactation, late menopause).
The use of exogenous estrogens, radiation exposure, alcohol
consumption, higher educational level and socioeconomic
status are also well-known risk factors for the disease
22. 2.2.1 Ionizing radiation
well-established mammary carcinogen.
Increased breast cancer risk has been shown following :
- acute radiation exposure from the atomic bombings in Japan
- high cumulative doses associated with the treatment of some
diseases and multiple diagnostic radiographic examinations
23. 2.2.2 Organochlorines
classic examples of persistent organic pollutants, have been of
worldwide concern owing to their
persistence, bioaccumulative ability, and potential negative
impacts on humans and animals.
strongly lipophilic and resistant to biotransformation.
have half-lives of up to several decades in human tissue.
relationship between organochlorines and breast cancer risk are
not consistent.
exposure to DDT early in life may increase the risk of breast
cancer.
24. 2.2.3 AGE
the most significant risk factor for breast cancer. rare in women
younger than 25 years.
The incidence increases with age, doubling about every 10 years
until the menopause, when the rate of increase slows
dramatically.
Women who start menstruating early in life or who have a late
menopause have an increased risk of developing breast cancer.
Women who have a natural menopause after the age of 55 are
twice as likely to develop breast cancer as women who
experience the menopause before the age of 45
25. AGE…. Cont…
Nulliparity and late age at first birth both increase the lifetime
incidence .
The risk of breast cancer in women who have their first child
after the age of 30 is about twice that of women who have their
first child before the age of 20.
The highest risk group are those who have a first child after the
age of 35.
An early age at birth of a second child further reduces the risk of
breast cancer
26. 2.2.4 Diet
an association between these dietary factors and breast cancer has
been largely inconsistent.
not found an overall association between breast cancer and total
intake of fat or any specific type of fat.
Whereas diets high in fat have been shown to increase the
occurrence of mammary tumors in rodents.
high consumption of meat may increase risk of breast cancer.
phytoestrogens, compounds found in foods such as
soy, broccoli, and berries, may substantially reduce the risk of
breast cancer
27. 2.2.5 Alcohol
alcohol drinking modifies the risk of numerous diseases.
3.6% of all cases of cancer and a similar proportion of cancer
deaths are attributable to alcohol drinking.
60% of cancers attributable to alcohol occur in the breast.
consumption of one drink per day or less does not increase risk of
breast cancer.
women who consume an average of 4 or more drinks per
day, regardless of the type of alcohol, may be at a 50% higher
risk of breast cancer than those who do not drink alcohol
28. 2.2.6 Tobacco smoke
Most studies have found no link between cigarette smoking and
breast cancer. Some studies have suggested smoking increases
the risk of breast cancer, but this remains controversial.
An active focus of research is whether secondhand smoke
increases the risk of breast cancer.
29. 2.2.7 Electromagnetic Fields (EMFs) and
Artificial Light
It has been hypothesized that increased exposure to
electromagnetic fields and light at night is associated with
increased breast cancer risk.
Most studies do not show a relationship .
30. 2.2.8 Viruses
Epstein-Barr virus (EBV) has been associated with the
development of several cancers in humans.
Another virus, mouse mammary tumor virus (MMTV), induces
mammary tumors in mice.
Studies have detected DNA sequences from both of these viruses
in human breast cancer cells, but not in normal breast tissue.
One recent study found that the EBV virus was more frequently
associated with aggressive breast tumors.
31. Prevention of Breast Cancer
There are two important aspects in breast cancer prevention: early
detection and risk reduction.
Screening may identify early noninvasive cancers and allow
treatment before they become invasive or identify invasive
cancers at an early treatable stage.
But screening does not, per se, prevent cancer.
Lifestyle changes, a healthy antioxidant-rich diet, exercise, and
weight reduction can help reduce a woman's risk of developing
breast cancer.
32. Prev… cont…
Mammography and breast self-examinations are crucial steps in
breast cancer prevention .
In extremely high-risk patients, such as those who have BRCA
mutations, risk reduction may involve prophylactic surgical
removal of the breasts and ovaries.
33. CONCLUSION
Breast cancer is a complex disease, which is associated with both
genetic and environmental risk factors. Breast cancer is far the
most frequently diagnosed neoplasm in women. Each
year, over 1 million new cases and 46,000 deaths occur
worldwide.
The highest incidence rates are found in industrialized
countries, including the US, Northern Europe, and
Canada, while lower rates are found in Asia and Africa
A number of risk factors for the development of breast cancer
have been identified.
34. Conc…. Cont….
The most common cause of hereditary breast cancer is an
inherited mutation in the BRCA1 and BRCA2 genes.
Other gene mutations can also lead to inherited breast cancers.
These genes include ATM gene, p53 tumor suppressor
gene, PTEN gene, and STK11 gene.
Environmental factors also play an important role in the etiology
of breast cancer.
These environmental factors are Ionizing
radiation, Organochlorines, age, diet, alcohol, Tobacco
smoke, Electromagnetic Fields (EMFs) and Artificial
Light, and Viruses
35. RECOMMENDATIONS
• There is a very low awareness of breast cancer in developing
regions. So there should be a massive work for increasing
awareness in the developing regions.
• There is low rate of detection of breast cancer which in turn
decreases the prevalence especially in developing countries.
So the detection rate should be increased.
• Work for further understanding of breast cancer etiology, and
specifically the relationship between breast cancer and the
environment.
36. Recom… cont…
• For women at high risk, routine screening should be initiated
sooner. For those with breast cancer genetic mutations,
mammography should begin at age 25, or at an age 10 years
younger than the youngest case diagnosed in the family
• Lifestyle modifications is important such as have your babies
earlier than later, Reduce your fat intake, Eat soy, Stop
drinking alcohol so much, Stop smoking, decrease exposure to
radiation, and chemicals like organochlorines.
37. REFERENCES
1. Ferlay J. Cancer Incidence, Mortality and Prevalence
Worldwide, IARC Cancer Base; 2009, 5:2-4
2. Stewart. World Cancer Burden. Lyon, France: IARC
Press, 2009, 33:6-9.
3. Bray F. cancer incidence, mortality and prevalence worldwide.2010;
231:46-49.
4. Struewing J.P. The risk of cancer associated with specific mutations
of BRCA1 and BRCA2 among Ashkenazi Jews. N. Engl. J.
Med, 2009, 336: 1401–1408.
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38. ACKNOWLEDGEMENT
University of Gondar, School of Biomedical and Laboratory
Science.
my advisors : Mr. Wubet Birhan
Mr. Yitayal Shiferaw
Mr. Belay Anagaw