UNIVERSITY OF GONDAR COLLEGE OF MEDICINE AND HEALTH SCIENCES SCHOOL OF BIOMEDICAL AND LABORATORY SCIENCETITLE: A Review on Genetic and Environmental Factors for Breast CancerNAME OF THE STUDENT: ALEMAYEHU ABATENAME OF ADVISORS: MR.WUBET BIRHAN, MR. YITAYAL SHIFERAW, MR. BELAY ANAGAW NOV, 2011 GONDAR, ETHIOPIA
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.
INTRODUCTIONBreast cancer is a malignant tumor that starts in the cells of the breast.occurs almost entirely in women, but men can get it, toois a major health burden worldwide.most common cause of cancer in both high-resource and low- resource settings
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 yearhoped that identification of genetic and environmental factors that contribute to the development of breast cancer will enhance prevention efforts
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.
ObjectiveThe objective of this paper is to compile the current literature about the genetic and environmental factors for breast cancer.
Global Breast Cancer BurdenBreast 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 regionsBreast 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).
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 deathsAnnual 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.
Breast cancer in AfricaAlthough 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)
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
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).
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.
Breast cancer in EthiopiaBreast 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 .
2. Genetic and Environmental Factors2.1 Genetic factors for breast cancers2.1.1 BRCA1 and BRCA2 genesAbout 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.
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.
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
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 .
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 syndromePeople 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.
2.1.4 PTEN genenormally 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
2.1.5 STK11 geneDefects 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
2.2. Environmental risk factorsThe 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
2.2.1 Ionizing radiationwell-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
2.2.2 Organochlorinesclassic 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.
2.2.3 AGEthe 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
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
2.2.4 Dietan 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
2.2.5 Alcoholalcohol 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
2.2.6 Tobacco smokeMost 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.
2.2.7 Electromagnetic Fields (EMFs) and Artificial LightIt 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 .
2.2.8 VirusesEpstein-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.
Prevention of Breast CancerThere 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 womans risk of developing breast cancer.
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.
CONCLUSIONBreast 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 AfricaA number of risk factors for the development of breast cancer have been identified.
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
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.
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.
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ACKNOWLEDGEMENTUniversity of Gondar, School of Biomedical and Laboratory Science.my advisors : Mr. Wubet Birhan Mr. Yitayal Shiferaw Mr. Belay Anagaw