International Journal of Scientific & Engineering Research, Volume 1, Issue 2, November-2010 1

ISSN 2229-5518

Computer Aided Screening for Early

Detection of Breast Cancer using BRCA
Gene as an Indicator
S.Ranichandra
Abstract: A mass of breast tissue that is developing in an abnormal, uncontrolled way is the cancerous
breast tumor. The early detection of breast cancer is a key for survival because of its association with
augmented treatment options. Mammography screening and MRI are some of the existing breast cancer
detection methods. MRI has problem of resulting more number of false positives. Mammogram has
disadvantages like expensive, false positives for patients with dense breast tissues, detects only if tumor size
bigger than 5mm and painful. Hence there is a need to develop more convenient and accurate method. In this
proposed approach, we analyzed gene expression patterns in blood cells for detecting the breast cancer in
the early stage. BRCA gene is a tumor suppressor gene which all people have. The BRCA DNA sequences from
patients are generated by PCR method and used as input in the local sequence alignment program which is the
implementation of Smith waterman algorithm. It compares the patient's gene sequence with the reference
BRCA gene sequence to determine the cancer risk at a very early stage.

Keywords: Breast cancer, early detection, Tumor suppressor genes, BRCA, blood sample, PCR method, DNA
sequencing, gene sequence, Local sequence alignment algorithm, Smith waterman.

Swelling or a lump in the armpit

1. INTRODUCTION
Breast cancer is a malignant tumor that starts from
cells of the breast. A malignant tumor is a group of
cancer cells that may grow into (invade) surrounding
tissues or spread (metastasize) to distant areas of the
body. The disease occurs almost entirely in women,
but men can get it, too [3]. It is the second most
common cancer that causes death in white, black,
Asian/Pacific Islander, and American Indian/Alaska
Native women. According to the report 2009-2010,
in 2009, an estimated 192,370 new cases of invasive
breast cancer was diagnosed among women and
approximately 40,170 women were expected to die
from breast cancer [2]. Staging is a method that
has been developed to describe the extent of cancer
growth. In general, the lower the stage, better the!
person's prognosis [5].Early detection of breast
cancer can improve the chances of successful
treatment and recovery. Mammography
screening is the most reliable method to detect
breast cancer in asymptomatic patients. It is
extremely important to catch breast cancer at an
early stage. Few of the main symptoms of breast
cancer are:
Change in the size or shape of a breast
Dimpling of the breast skin
The nipple becoming inverted
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2. PROBLEM DESCRIPTION
Although highly effective, it has significant
limitations like, in the absence of micro
calcification, mammography often fails to detect
tumors that are less than 5 mm in size, and also
mammograms of women with dense breast tissue
are difficult to interpret. For example, in a study of
over 11,000 women with no clinical symptoms of
breast cancer, the sensitivity of mammography was
only 48% for the subset of women with! extremely
dense breasts, compared with 78% sensitivity for
the entire sample of women in the study. So there is
a need to develop more accurate, convenient and
objective detection method [12].Comparing patient
BRCA gene with the original gene is the identified
method in the proposed approach. Gene is a stretch
of DNA, so DNA sequences are compared to
identify cancer risk. The sequence comparison is
executed using the dynamic programming algorithm
for local alignment between two DNA sequences
proposed by Smith and Waterman called smith
waterman algorithm is a very well known and
versatile algorithm [16].
3. EXPERIMENTAL STUDY OF BRCA GENES
The official name of BRCA 1 gene and BRCA2
gene are breast cancer susceptibility gene 1 and
International Journal of Scientific & Engineering Research, Volume 1, Issue 2, November-2010
ISSN 2229-5518
breast cancer susceptibility gene 2, respectively. The
BRCA genes belong to a class of genes known as
tumor suppressor genes [10]. Like many other
tumor suppressors, the protein produced from the
BRCA genes helps prevent cells from growing and
dividing too rapidly or in an uncontrolled way.
There is no strong homology between BRCA1 and
BRCA2, although both genes have a large exon 11
which seems to be crucial for function. However,
the function of the two genes seems to be similar
[14, 20]. The BRCA genes provides instructions
for making a protein that is directly involved in
repairing damaged DNA. By helping repair
DNA, BRCA 1 plays a role in maintaining the
stability of a cell's genetic information [13]. It
is identified that more than 1,000 mutations in the
both genes have a large exon 11 which seems to be
crucial for function. However, the function of the
two genes seems to be similar [14, 20]. The
BRCA genes provides instructions for making a
protein that is directly involved in repairing
damaged DNA. By helping repair DNA, BRCA
plays a role in maintaining the stability of a cell's
genetic information [13].
It is identified that more than 1,000
mutations in theBRCA1 gene and 800 mutations
in the BRCA2 gene are possible, many of which
are associated with an increased risk of breast
cancer. Most of these mutations lead to the j
production of an abnormally short version of the
BRCA1 protein, or prevent any protein from
being made from one copy of the gene. Other
BRCA1 mutations change single j protein building
blocks (amino acids) in the protein or delete large
segments of DNA from the BRCA1 gene. Many
BRCA2 mutations insert or delete a small number
of DNA building blocks (nucleotides) in the gene.
Researchers believe that a defective or missing
BRCA1 protein is unable to help repair damaged
DNA or fix mutations that occur in other |genes.
As these defects accumulate, they can allow cells
to | grow and divide uncontrollably and form a tumor
[8, 9].
4. SEQUENCE COMPARISON
Sequence comparison can be defined as the
problem of J finding which parts of the sequences
are similar and which parts are different. Generally,
a measure of how similar they are is also desirable. A
typical approach to solve this problem is to find a
good and plausible alignment between the two
sequences. Then, given an appropriate scoring
scheme, their similarity can be computed. Generally,
sequence comparisons involve aligning sections of
the two sequences in a way that exposes the
similarities between them [7]. The idea of
aligning two sequences (of possibly different
sizes) is to write one on top of the other, and break
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them into smaller pieces by inserting spaces in one
or the other so that identical subsequences are
eventually aligned in a one-to-one correspondence
naturally, spaces are not inserted in both sequences
at the same position. The objective of sequence
alignment is to match identical subsequences as far
as possible. However, if the sequences are not
identical, mismatches are likely to occur as different
letters are aligned together. The insertion of spaces
produced gaps in the sequences. They are important
to allow a good alignment between the characters of
sequences. A gap in the first sequence is considered an
insertion of a character from the second sequence into
the first one, whereas a gap in the second sequence is
considered a deletion of a character of the first
sequence.
Once the alignment is produced, a score | can be
assigned to each pair of aligned letters, called aligned
pair, according to a chosen scoring scheme. The
similarity of two sequences can be defined the
best score among all possible alignments between
them. Sequence comparison is actually a well-
know problem in computer science.
Computational approaches to sequence alignment
generally fall into two categories: global
alignments and local alignments. Pair wise
sequence alignment methods are used to find the
best-matching piecewise (local) or global
alignments of two query sequences. Pair wise
alignments can only be used between two
sequences at a time, but they are efficient to
calculate and are often used for methods that do
not require extreme precision (such as searching
a database for sequences with high similarity to a
query). The three primary methods of producing
pair wise alignments are dot-matrix methods,
dynamic programming, and word methods.
Global alignment is achieved using the
Needleman-Wunsch algorithm. The algorithm it
tries to take all of one sequence and align it with
all of a second sequence. Short and highly
similar subsequences may be missed in the
alignment because they are outweighed by the rest
of the sequence. Hence, one would like to create
a locally optimal alignment [18]. Local
alignments are more useful for dissimilar
sequences that are suspected to contain regions of
similarity or similar sequence motifs within their
larger sequence context. The Smith-Waterman
algorithm is a general local alignment method also
based on dynamic programming. The dynamic
programming approach to pair wise sequence
alignment is guaranteed to provide the optimal
global or local pair wise alignment and score given
a particular scoring scheme [1]. In smith waterman
algorithm,
1. All symbols (residues) in the two
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ISSN 2229-5518

sequences have to be in the

alignment, and in the same order
they appear in the sequences
2. We can align one symbol from one
sequence with one from another
3. A symbol can be aligned with a
blank ('-')
4. Two blanks cannot be aligned [6, 15,
17]

5. PROPOSED SYSTEM

DNA sequencing is the first step of sequence

analysis. DNA sequencing refers to sequencing
methods for determining the order of the nucleotide
bases-adenine, guanine, cytosine and thymine in a
molecule of DNA. DNA Sequencing can be
performed using PCR .Steps in DNA sequencing
are

1. Extract genomic DNA

2. Amplify known gene region
3. Verify successful PCR amplification
4. Clean PCR products
5. Quantify DNA concentration
6. Cycle sequence

Precipitate cycle- sequenced products and submits

them. Consecutively, the obtained DNA sequence
is used as Input
in the local sequence alignment program, Smith
waterman [11]. The system flow diagram is shown in Fig 1 System Flow Diagram
Fig 1.

5.1. Smith waterman Algorithm

5.2. Working principle of the algorithm
A matrix H is built as follows:
1. Assigns a score to each pair of bases
H(i,0) = 0, 0 <= i <= m a. Uses similarity scores only
b. Uses positive scores for related
H(0, j) = 0,0 <= j <= n residues
c. Uses negative scores for
H (i , j) = max { 0
substitutions and gaps
i
H(i-,j, j-l)+w(a „bj) Match/Mismatch 2. Initializes edges of the matrix with zeros
H(i-1,j) + w(ai ,- ) Deletion 3. As the scores are summed in the matrix,
H(I,j-1) + w( , bi) Insertion any score below 0 is recorded as 0
} 1<=i<=m, 1<= j<= n 4. Begins the trace back at the maximum
value found anywhere in the matrix
J
Where: 5. Continues until the score falls to 0.
This algorithm will give the place of mismatch
a, b = Strings over the Alphabet S and with those results presence or absence of
m = length(a) cancer can be I confirmed [4, 19].
n = length(b)
H(i j) - is the maximum Similarity-Score 6. IMPLEMENTATION AND RESULT ANALYSIS
between a suffix of a[l...i] and a suffix of
b[l...j] The program is implemented in JAVA. The
w(c,d), c, d € Z U ~[ ‘-‘],’-‘ is the gap-scoring DNA sequence generated by PCR is used as an
scheme . input for the proposed detection method. The

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International Journal of Scientific & Engineering Research, Volume 1, Issue 2, November-2010
ISSN 2229-5518
implemented program will read the content of the
file and compares the input DNA sequence with
the reference gene sequence file. If the mismatch
is null, the sequence is same therefore the patient is
healthy which is evident from Fig 2.
Fig. 3 shows that patient sequence does not match with original
sequence and hence patient has cancer risk
Otherwise, there is mismatch value and so patient
is in cancer risk therefore patient has to be
recommended for treatment, is shown in Fig 3. The
Graph (Fig 4) signifies the early detection of
cancer and survival rate.
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4
Fig 4 survival rate of patients(5 year relative) in early
detection of breast cancer (Source: American
cancer Society)
7. CONCLUSION
The proposed approach for early detection of
breast cancer using local sequence alignment
technique identifies whether patient is affected by
cancer or not. Furthermore, the risk level of cancer
in affected patients is also determined.
Consequently, this early detection method using
DNA sequencing has significantly advantageous
than other methods since cancer risks can be
identified in the early stage, even before the
symptoms are clearly observable. Moreover, this
method is beneficial as a consequence of its ease
of use, economical with respect to laboratory
usage and reliable as genes are used for
detection. The proposed approach has 95%
efficiency in detecting breast cancer in early
stage. This project assures more effective and
accurate method and aims towards breast cancer
detection in early stage.
8. FUTURE SCOPE
The current evaluation system has potential
outcome in observing the cancer risk of patient.
The smith waterman algorithm is effective for
text string matching, but an assessment is
required to determine the proportional benefits of
the algorithm with the traditional techniques and
other sequencing algorithms. Thought smith
waterman algorithm is very sensitive and accurate,
it has more time complexity and it needs large
memory space. As the biological sequencing data
are rapidly expanding, the memory requirement
has become a critical problem in the existing
International Journal of Scientific & Engineering Research, Volume 1, Issue 2, November-2010 5
ISSN 2229-5518

smith waterman algorithm. The future work can
target to use the upgraded Smith waterman
algorithm, that has reduced computational
complexity to (N*(M+l)/2) and less size and
space complexity. Moreover, risk level of cancer
can also be identified in further computational
analysis.
[17]. "Smith Waterman algorithm" Oct. 4, 2007
[18]. Wikipedia, "Smith Waterman algorithm,"
WikipediaH April 2010.
[20]. Wisegeek, "What is a tumor suppressor gene
wisegeek, 2009.

ABBREVATIONS

BRCA1 Breast cancer 1, early onset

BRCA2 Breast cancer 2, early onset
PCR Polymerase Chain Reaction
DNA Deoxyribonucleic acid

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[7]. Eugene W. Myers, "An Overview of Sequence
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[8]. Genetic Home Reference, "BRCA1", Genetic
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[12]. P. Sharma et al, "Early detection of breast
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[13]. Ralph Scully, "Role of BRCA gene dysfunction
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