Among all forms of cancers, Breast
cancer is the most common type of cancer in females worldwide. In fact, it is
the 2nd leading cause of death among female population. The situation is more alarming in
Pakistan as the incidence rate of breast cancer is higher among Pakistani
females compare to other countries of Asia, i.e., it accounts for one in nine
Pakistani female population. More precisely, as compared to its neighboring
countries, Iran and India, the chances of breast cancer in Pakistani women are
2.5 times higher. The objectives of this mini-review were to gather literature
regarding the most common risk factors attributed to breast cancer in Pakistani
women, to determine disease knowledge of the population regarding breast cancer
and to provide awareness about breast cancer to the general population.
FACTORS ATTRIBUTING BREAST CANCER:
With the increase in frequency of
diagnosis of breast cancer in Pakistani women, it is important to point out the
basic etiology of breast cancer. Breast cancer etiology is a complex of
genetic, environmental and lifestyle factors and there are variations in
diversity of these factors among areas, therefore it highlighted the need for
study of this diversification for each geographical area. Considering this, the
focus is made on involvement of variety of risk factors in breast cancer
etiology was explored in Pakistani population.
Physiological factors that are
considered as a risk factor of breast cancer are:
Gender: Just Being a women is one of
the most fundamental but unavoidable risk factor of breast cancer. It means
that women are at greater risk than men. The possible reason for this might be
the female sex hormones, estrogen and progesterone, which promote growth of
breast cancer cells.
Age: Another unavoidable physiological
risk factor for developing breast cancer is the increasing age. A case control
study was determined to study the effect of various factors, including age, on
the development of breast cancer. The risk factors investigated were age,
demographic, social, menstrual, reproductive, and genetic histories. Total 115
patients were studied and interviewed from different hospitals of Karachi. It
was observed that age group of 41 to 50 years were at the highest risk of
developing breast cancer (Safila et al., 2014).
Obesity: Being over-weight is another
factor that predisposes women to breast cancer development. As mentioned
earlier, the possible reason for increased risk of breast cancer in women is
the presence of female sex hormones, estrogen and progesterone. Once ovaries
are unable to secrete estrogen (i.e., menopause), the most prominent source of
a woman's estrogen is then adipose tissues. Thus estrogen level is directly
proportional to the body’s fat content, and obesity, thus, increases ones
chance of getting breast cancer. Different studies supported the link of breast
cancer with high basal metabolic rate (BMI) (Bhurgri et al., 2007, Zhu et
al., 2005 and Rabia et al., 2013).
Social And Environmental Factors that
can be the major factor for breast cancer are:
Smoking: Smoking also increases the
risk of developing breast cancer. Different Studies have shown the link between smoking and breast
cancer. Six months study was conducted in NORI to assess the role of smoking as
breast cancer risk factor. Study population included 300 females; 150 of which
were breast cancer patients and the rest were their age-matched non-cancerous
women who attended the NORI. It was observed that smoking is most significantly
associated with breast cancer in patients attending NORI (Faheem et al.,
2007). Similar results were also observed by Gillani et al., 2006.
Family History: Family history is also
very important risk factor. Close female relatives of patients are at greater
risk of developing breast cancer. If the patient is your close relative like
your sister, mother and daughter than your risk is doubled (Gillani et al.,
Nutritional Status: Nutritional Status
is also very important. Studies have shown that fat-soluble Vitamin D is a naturally occurring
anti-proliferative compound. Human genes
contain vitamin D response elements that encode for proteins important in
regulation of cell differentiation, proliferation and angiogenesis. Vitamin D
shows its anti-cancer effect by binding to vitamin D receptor (VDR) found in
various tissues and cells. Thus, lack of vitamin D intake can be considered as
risk of breast cancer (Shamsi et al., 2013).
Reproductive Factors: Reproductive
factors are also very important to consider. Study have shown that women who
started menstruating early (i.e., early menarche, before 12 years of age)
and/or went through menopause later (i.e., late menopause, after 55 years of
age) are at increased risk of developing breast cancer. The possible reason for
this might be the increased exposure to female sex hormones, estrogen and
Nulliparity: Nulliparity is another
factor associated with breast cancer. A case control study was performed in
Mayo Hospital Lahore, from October 2008 to April 2009. Menstrual and
reproductive history was taken from both 150 breast cancer patients and 300
controls. Results showed that age at menarche had no association with breast
cancer for both pre and postmenopausal women, but nulliparity was a risk for
both pre and postmenopausal. Furthermore, it was concluded that majority of
risk factors for pre and postmenopausal are also associated with postmenopausal
breast cancer except less parity that is important for menopausal breast cancer
only (Butt et al., 2012). In another study it was found that single marital
status and older age at menopause conferred an increased risk of breast cancer
for women. On the other hand, increasing parity decreased the breast cancer
risk (Shamsi et al., 2013).
Increased age at first live birth and
lack of breastfeeding: Increased age at first live birth and lack of
breastfeeding have also been linked to increased breast cancer risk (Butt et
al., 2012). Breast feeding causes hormonal alterations, like decrease in the
level of estrogen and removal of possible carcinogens stored in the fatty
breast tissue, which collectively develop the resistant to mutations in the
cells that can lead to cancer.
High ratio of incomplete pregnancies
also significantly increases breast cancer risk (Rabia et al., 2013). As
discussed, the possible reason might be the increased exposure to female sex
ETIOLOGY OF BREAST CANCER:
Body cells are continuously dividing
into new cells, and even die. There are several genes that control the growth
of cells. Among these are the oncogenes that promote cell division, and tumor
suppressor genes that slow down the cell division, or cause the cell to die at
right time. Mutation/changes in the nucleic acids that either activates
oncogenes or inhibits tumor suppressor genes can cause normal breast cells to
become cancerous .
Breast cancer susceptibility is largely
‘polygenic”, which means breast cancer is found to be associated with inherited
mutation of high penetrance genes (BRCA1 and BRCA2) as well as large number of
moderate/low penetrance genes in populations of diverse ethnicities.
Polymorphisms of a single nucleotide in many genes have also been associated
with high morbidity and susceptibility to breast cancer.
Little work has been done only in
Chinese population among Asians, and scarcely on women of Pakistan, to
determine the association of genetic factors with breast cancer. Among
Pakistani women breast cancer has been identified as the most common
malignancy, accounting for 34.6% of all female cancers and genetic factors are
suggested to play a key role. To estimate the contribution of genetic factors,
a case-control study was conducted in 2002 on 341 breast cancer patients and
200 female control subjects. Data analysis concluded that mutation in BRCA2
genes was observed in 6.7% patients and mutations of the BRCA1 gene were
observed in 65% of patients. It was also observed that five mutations of BRCA1,
i.e., 2080insA, 3889delAG, 4184del4, 4284delAG, and IVS14-1A->G, and one
mutation of BRCA2, i.e., 3337C->T, were recurrent in case subjects and
represented candidate founder mutations (Foulkes et al., 2002).
Interestingly, majority of detected mutations were unique to Pakistani
population. Prevalence of BARCA1 and BARCA2 mutations in Pakistani females was
also studied by Rashid et al., 2006 and somewhat similar results were
obtained (Rashid et al., 2006).
Along with BARCA1 and BARCA2 genes,
recent research showed presence of other
genes that lead to breast cancer, as shown by the results of Farooq et al.,
2011. They formulated the database report on BARCA1 and BARCA2 variants in
Pakistani population, aiming to check the contribution of genetic modification
in prevailing breast and ovarian cancer. Percentage involvement of BARCA1 and
BARCA2 gene was estimated. Nine percent of these cancers showed alterations in
BRCA1 gene while 3% have shown BRCA2 variants while the remaining 88% of breast
and ovarian cancers can be due to the involvement of other genes (Farooq et
Positive family history reflects
inherited mutated genes that may be due to intra-family marriages. Studies
conducted in Pakistan showed high risk of breast cancer due to consanguineous
marriages (Gillani et al., 2006 and Shamsi et al., 2013).
To study the role of
estrogen-metabolizing pathway and estrogen receptor pathway in the development
of breast cancer, a case control study was conducted on 100 breast cancer
female patients and 100 control samples aged 15-65 years. It was observed that
Polymorphism of genes involving estrogen-metabolizing pathway and estrogen
receptor pathway also play an important role (Ali et al., 2011).
FOR THE FUTURE:
Incidence and prevalence of breast
cancer is higher among Pakistani females compare to other countries of Asia.
There are many factors that play important role in the development of breast
carcinoma; however, the focus should be given to find out the genetic factors
causing breast cancer in Pakistani population in order to prevent and decrease
its incidence. Furthermore, to prevent breast cancer hazards, there is a need
for early diagnosis of cases. The development of effective screening program at
the government level will be helpful in not only prevention and treatment of
breast cancer, and subsequently it will also improve prognosis in these
patients. Education of public is highly important to boost cancer awareness for
prevention, early diagnosis and treatment. Female awareness should be increased.
Training should be given to younger age group in the colleges and schools for
breast self-examination (BSE). Media should play their role to provide
awareness among general population. Breast care clinics and screening
programmes should be started in all hospitals. Last, but not the least, all
concerned people like Tibb Physician (Hakeem), Homeopaths and other alternate
therapists should be provided awareness for early referral of such patients to
the tertiary referral hospitals.
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