Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018

Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."

Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018

Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."

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Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018

Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
Knowledge is treasure of a wise man. The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
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Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
On Sep 2018

Dr. Arunava Biswas

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Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
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Calcutta National Medical College & Hospital , Kolkata

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Muzaffarnagar Medical College,
On Aug 2018

Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".

Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
On Aug 2018

Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help ones reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".

Dr. Mamta Gupta
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018

Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.

Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journalsNo manuscriptsNo authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."

Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
On May 11,2011

Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."

Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
On April 2011

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.

Dr. Anuradha
On Jan 2020

Important Notice

Year : 2012 | Month : May | Volume : 6 | Issue : 3 | Page : 498 - 502 Full Version

Genetic Basis of Breast Cancer

Published: May 1, 2012 | DOI:
R.S. Khane

Associate Professor of Physiology Department of Physiology, D.Y. Patil Medical College, Kolhapur

Correspondence Address :
Dr. R.S. Khane
‘Paras,’ A-5 Bunglow, Evergreen Homes,
Nagala Park, Kolhapur.
Phone: 9890045256


Breast cancer is the commonest cancer in women worldwide. Today, there is no woman in the world who is at a truly low risk of developing the disease. In India, the growing epidemic of breast cancer presents a major challenge to the global public health, especially, given the failure to cope with the current situation. The burden of breast cancer will continue to increase, not only in terms of the absolute number of cases, but also in terms of its incidence. It has long been observed that 5 to 10% of the breast cancers are the result of an inherited familial predisposition. So, the precise knowledge of the underlying genetic processes is useful for the early detection and prevention of breast cancer. As mammography will be difficult to be implemented in India for various reasons and also because of its complex nature and high cost, genetic testing is not presently routinely available in India. So, efforts should be made to detect breast cancer at an early stage by educating the people about the risk factors and screening methods like Breast Self Examination, because late stage presentation is the main problem in India, which leads to a poorer prognosis. In this review, the risk factors for the development of breast cancer, the role of various genes in the pathogenesis of breast cancer, the possible options for high risk women and the socio-cultural issues regarding breast cancer have been outlined.


Breast cancer, genetics, risk factors, BRCA1

What is Cancer?
Cancer is sometimes caused by alterations in the genes and / or in the expression of genes. The gene mutations in most of the cancers arise in the somatic cells and they are transmitted to the successive generations of cancer cells. In about 5-10% of the cancers, the disease is transmitted from a parent to the offspring. Such types of inherited cancers are rare. Approximately 50 heritable cancer syndromes are known. These syndromes provide an opportunity to understand the genetic basis of cancers and the role of various genes in their pathogenesis. As the cell divides and re-divides, more and more genes get mutated, thus providing the cell with the potential to become more malignant. Thus, the development of a cancer is a multistage process.
What is Breast Cancer?
The term “breast cancer” refers to a malignant tumour that has developed from cells in the breast. Usually, breast cancer either begins in the cells of the lobules, which are the milk-producing glands, or in the ducts, the passages that drain milk from the lobules to the nipple. Less commonly, breast cancer can begin in the stromal tissues, which include the fatty and fibrous connective tissues of the breast.
Why Breast Cancer is Important?
The incidence of breast cancer in India is on the rise and it is rapidly becoming the number one cancer in females, pushing cervical cancer to the second spot. The seriousness of the situation is apparent from the recent data from the Indian Council of Medical Research (ICMR), where it is reported that one in twenty two Adolescent Section women in India is likely to suffer from breast cancer during her lifetime , while the figure is definitely more in America, with one in eight women being the victims of this deadly type of cancer (1).
World: It has been estimated that about 9 million new cancer cases are diagnosed every year and that over 4.5 million people die from cancer each year in the world. The worldwide incidence of breast cancer comprises 10.4% of all the cancer incidences among women, making it the second most common type of nonskin cancer (after lung cancer) and the fifth most common cause of cancer death (2). In 2004, breast cancer caused 5,19,000 deaths worldwide (7% of all the cancer deaths and almost 1% of all the deaths) (3). Breast cancer is about 100 times more common in women than in men, although males tend to have a poorer outcome due to delays in the diagnosis (4).
India: The estimated number of new cancers in India per year is about 7 lakhs and over 3.5 lakhs people die of cancer each year. Out of these 7 lakhs new cancers, about 2.3 lakhs (33%) cancers are tobacco related. The data from the National Cancer Registry Program shows that in all the urban areas of India, breast cancer has now surpassed cervical cancer as the most frequently diagnosed cancer in women. The most recent data which was available from the National Cancer Registry Program showed a wide variation in the age standardized incidence rates which were observed between the rural and urban populations, which ranged from 36.1 in Bangalore to 7.2 in the Sikkim state. The age standardized mortality rate for breast cancer in India is 11.1 per 100000 (12.5 per 100000 globally). As in other developing regions, the mortality rates for breast cancer in India are high in comparison to its incidence rates. A poor survival may be largely explained by the lack of or limited access to the early detection services and treatment.
Risk Factors
The causes of the growing breast cancer epidemic are complex and are not well understood, which makes finding ways to prevent breast cancer elusive. Many experts blame the “westernization” of the developing world. “Westernization” has many positives, for it brings an increased life expectancy, an improved socio-economic status, and greater freedom for women. But it also has some negatives: changes in the diet and as more women take up sedentary jobs, less exercise, early menarche, delayed childbirth, families with fewer children, less breast feeding, and hormone replacement therapy – all are thought to increase the risk of breast cancer. The reasons for the recent observed increase in the incidence of breast cancer in the Indian population are not clearly understood, but it has been thought to be largely explained by the ‘westernization’ of the lifestyles and changes in the reproductive behaviour. There is no way for us to prevent breast cancer, but we can definitely detect it early and treat it adequately. Achieving this in a society will lead to a better “long-term” survival as well as a better quality of life. The risk factors for developing breast cancer are sex , age or lack of childbearing or breast feeding (5) and higher hormone levels. “We used to think that breast cancer was a problem of only wealthy women, but now we know that breast cancer shows no favorites: It strikes the rich and the poor women alike,” says Felicia Knaul, Ph.D., who heads the Harvard Global Equity Initiative and has produced a body of research on the issue. The big difference is that by the time the disease is diagnosed in poor women, it is often too late for effective treatment, which is the main problem in India. Genetic factors usually increase the risk slightly or moderately. The exception is women and men who are carriers of the BRCA mutations. These people have a very high lifetime risk for breast and ovarian cancers, depending upon the portions of the proteins where the mutation occurs. Generally, hereditary breast cancers are earlier in onset and they have a higher prevalence of bilateral breast cancer. Genetics has transformed the use of the family history into and it has led to the reemergence of the detailed family history. It is critical that public and professional educational efforts increase the family history awareness and that they facilitate some of the limitations which are associated with the conventional maternal history ascertainment, ultimately improving the health care and research. The increasing use of genetic screening promises to cultivate a paradigm shift in the medical treatment, emphasizing on primary prevention and an early intervention. Appreciation of the history is necessary to make this important advance. The literature has described that a familial association for breast cancer is very extensive. With reports of individual pedigrees and numerous case control studies, most investigators have found a 2-3 fold increase in the risk of breast cancer among the relatives of breast cancer probands as compared to women in the matched control samples or in the general population.
Genetic Basis of Breast Cancer
Breast cancer is a genetic disease which is caused by an alteration in the genes or in the expression of the genes. Cell division and cell death are governed by several genes which are known to cause cancers. The functions of proteins which are coded by genes which are implicated in cancers :
• A signaling pathway for cell proliferation
• Cytoskeletal components which are involved in the maintenance of contact inhibition
• Regulation of the cell cycle
• Programmed cell death (apoptosis )
• DNA repair mechanisms
Families which are at a high risk need a closer surveillance for the cancer of the breast. Mutation detection in these families helps in the definitive identification of the carrier and thus, in the identification of the subjects who require a close “follow-up” and also those who do not.
Genes for Breast Cancer
BRCA1 (breast cancer1, early onset) is a human tumour suppressor gene which produces a protein called the breast cancer type 1 susceptibility protein. It is found in the cells of breast and other tissues, where it helps in repairing damaged DNA and in destroying the cells when their DNA cannot be repaired. If BRCA1 itself is damaged, the damaged DNA can let the cell duplicate without control, and this can turn into a cancer. The protein which is encoded by the BRCA1 gene combines with other tumour suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex which is known as the BRCA1-associated genome surveillance complex (BASC) (6). The BRCA1 protein associates with RNApolymerase II, and through the C terminal domain, also interacts with the histone cyclase complexes. This protein thus plays a role in the transcription DNA repair of double-stranded breaks, ubiquitination, transcriptional regulation, as well as other functions (7).
Gene Location
The human BRCA1 gene is located on the long (q) arm of chromo- some 17 at band 21, from base pair to 38,530,994 (map). BRCA1 orthologs have been identified in most mammals, for which the complete genome data are available.
Protein Structure
The BRCA1 protien (breast cancer type 1 susceptibility protein which is also known as the RING finger protein 53) contains the following domains:
• Zinc finger, C3HC4 type RING FINGER pfam00097
• BRCA1 C Terminus (BRCT) domainPfam Pf 0053
This protein also contains the nuclear localization signal and the nuclear export motif signal. Recent research has suggested that both the BRCA1 and the BRCA2 proteins regulate the activity of other genes and that they play a critical role in the embryo development. The BRCA1 protein probably interacts with many other proteins, including tumour suppressors and regulators of the cell division cycle.
Mutations and cancer risk
Certain variations of the BRCA1 gene can lead to an increased risk for breast cancer. Researchers have identified hundreds of mutations in the BRCA1 gene, many of which are associated with an increased risk of cancer. Women who have an abnormal BRCA1 or BRCA2 gene have up to an 85% risk of developing breast cancer by the age of 70; an increased risk of developing ovarian cancer is about 55% in women with BRCA1 mutations and about 25% in women with BRCA2 mutations. These mutations can be changes in one or a small number of DNA base pairs (the building blocks of DNA). These mutations can be identified by PCR and DNA sequencing.In some cases, large segments of DNA are rearranged. These large segments, also called as large rearrangements, can be a deletion or a duplication of one or several exons in the gene. The classical methods for mutation detection (sequencing) cannot reveal these mutations (8). Other methods which have been proposed: Q-PCR, Multiplex Ligation–Dependent Probe Amplification (MLPA) and Quantitative Multiplex PCR of Short Fluorescent Fragments (QMPSF). Newer methods have been recently proposed: heteroduplex analysis (HDA) by multi-capillary electrophoresis and also, the dedicated oligonucleotides array based on comparative genomic hybridization (array-CGH). Some results have suggested that the hypermethylation of the BRCA1 promoter which has been reported in some cancers, could be considered as an inactivating mechanism for the BRCA1 expression. A mutated BRCA1 gene usually makes a protein that does not function properly because it is abnormally short. Researchers believe that the defective BRCA1 protein is unable to help in fixing the mutations that occur in other genes. These defects accumulate and may allow the cells to grow and divide uncontrollably to form a tumour. In addition to breast cancer, mutations in the BRCA1 gene also increase the risk on ovarian, fallopian tube and prostate cancers. Moreover, precancerous lesions (dysplasia) within the fallopian tube have been linked to the BRCA1 gene mutations. Pathogenic mutations anywhere in a model pathway containing BRCA1 and BRCA2 greatly increase the risks for a subset of leukaemias and lymphomas. The BRCA2 gene is located on the long (q) arm of chromosome 13 at position 12.3 (13q12.3), from base pair 31,787,616 to base pair 31,871,804 (9). It is composed of 27 exons and it encodes a protein of 3418 amino acids. The types of mutations which are related to it are frameshift mutations (68%), nonsense mutations (12%), splice sites (7%) and missense mutations (13%).
Other Breast Cancer Genes
The TP53 gene: This gene is located on the short arm of the chromosome 17. It is a tumour suppressor gene. Germline mutations of TP53 account for over 70% of the cases of the Li – Fraumeni syndrome. The Li – Fraumeni syndrome is an autosomal dominant cancer syndrome. Families with the Li – Fraumeni syndrome are at a high risk for soft tissue childhood sarcomas, breast cancers, brain tumours, and adrenal cortical tumours. TP53 accounts for a very small proportion of breast cancers outside the Li – Fraumeni syndrome.
The ATM gene: Hetrozygote carriers of the ataxia telangiectasia gene are known to be at a five fold risk for breast cancer. It is located on chromosome 11q.
The PTEN gene: Cowden disease is a rare autosomal dominant syndrome in which the affected members tend to develop bilateral breast cancer, multiple facial trichelemmomas, acral keratosis, oral papillomas, gastrointestinal polyps, female genital tract tumours and thyroid tumours. The risk of breast cancer in women with Cowden disease is 30-50% by the age 50 years. It does not account for breast cancer outside the families who are affected by the Cowden disease. The gene for it is located on chromosome 10q. The available data and records till date, suggest that the families with breast cancers differ in their pattern of inheritance and the spread of the disease. Maurice et al (10), in their study, screened younger women with a family history of breast cancer. Their results strongly suggested that screening young women with a family history of breast cancer led to an improved survival. They also suggested that there should be further follow-up and other “sub-studies” regarding the screening of younger women with a family history of breast cancer to get a precise estimate of the risks and the benefits. Hampton and Maher (11) studied the pedigree analysis of breast cancer in Oklahoma Indian women. In their study, pedigrees were obtained in five of the nine women who had developed breast cancer between the ages of 25 and 45 years. There appeared to be no correlation between the blood quantum and the age of diagnosis of the breast cancer. It suggested that more pedigree analyses should be done to confirm the hypothesis that breast cancer had occurred in the younger Oklahoma Indian women. Rajeswari et al (12) studied the risk assessment in the first degree female relatives of breast cancer patients by using the alkaline comet assay. In their study, the comet assay was used to study the basal DNA damage, the DNA susceptibility to a mutagen (N-methyl N-nitro, N-nitrosoguanidine) and the DNA repair efficiency. A significant increase in the DNA damage (baseline and after treatment with a mutagen, as well as after allowing the repairs to take place) and the micronucleus frequency was observed in the controls and their First Degree Family Relatives (FDFRs ) and in the FDFRs of the breast cancer patients. Gajalakshmi et al (13) found a novel BRCA 1 mutation (in a group of 23 Tamil Nadu (south Indian) patients with a positive family history for breast and ovarian cancer). The 1301 de1T is a novel mutation that has not been documented in any population or in any published report to the best of our knowledge. The identification of this novel mutation stresses the need for developing a database of BRCA1 mutations, which will aid in the breast cancer screening in this population. In the study of Ford et al (14) the contribution of BRCA 1 and BRCA 2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families , each with at least four cases of breast cancer. It was observed that the lifetime risk of breast cancer appeared to be similar to the risk in the BRCA 1 carriers, but there was some suggestion of a lower risk in the BRCA 2 carriers, at 50 years of age. Cote et al (15) evaluated the risk of other cancers in individuals with a family history of pancreatic cancer. It was found that a family history of pancreatic cancer was associated with a doubled risk of lymphoma and ovarian cancer among the relatives after adjustment. The relatives with a family history of early – onset pancreatic cancer in a proband had a sevenfold increased risk of lymphoma. Couch et al (16) noted in their study that in their series, the BRCA 2 mutation accounted for 14% of the male breast cancers, all but one of which had a family history of male and / or female breast cancer. Armstrong and Davies (17) studied the pedigree of familial breast cancer. In their study report on several relatives who were suffering from breast cancer, the occurrence of neoplasms in 3 generations of a large family was carefully checked for. The members of one out of 8 branches were found to have a high incidence of breast cancer, with 6 women being affected, 4 of them being under the age of 40. They found an early age at onset for bilateral breast cancer, other tumours like ovarian cancer and benign breast disease in the family members.Teraoka et al (18) found an increased frequency of ATM mutations (miss-sense type) in breast carcinoma patients with an early onset disease and a positive family history. Fletcher et al (19) suggested that the clinical management of the daughter of a woman with bilateral breast cancer should depend on her CHEK 2 1100de1c carrier status. This and other moderate penetrance breast cancer susceptibility alleles, together with the family history data, will thus identify the increasing numbers of women who are at a potentially very high risk. But it is also important that before such predictions are accepted by clinical geneticists, a further population-based evidence should be obtained on the effect of CHEK 2 1100 de1c and other moderate penetrance alleles in women with a family history of breast cancer.
The Possible Options for High Risk Women
There are 3 methods for the early detection of breast cancer:
Mammography: Mammography i.e. the X-ray of the breast, should be done at regular intervals. But mammography is expensive and technology driven and it requires a stringent quality control and extensive experience on the part of technicians as well as doctors who are involved. If these are not available, mammography can do more harm than good by falsely diagnosing cancer or missing it when it is actually present. In women who are at a higher risk, a mammography surveillance, usually from the age of 35 years onwards, may be advisable. But currently, mammography screening is not advocated for allthe Indian women. Also, some studies have reported that at an earlier age, due to the dense breast tissue, mammography may miss the diagnosis of a breast lump.
Breast Self Examination (BSE): If it is done properly, it is as effective as mammography. The education about this should be initiated in the women in their midteens itself. This involves a description of the natural history of Hereditary Breast Cancer (HBC). At the age of 18 years, they should be taught breast self examination. They should then be told in detail about the pros and cons of genetic testing. The mutation detection test of the “at-risk” women clears the uncertainties and identifies the mutation carriers who are at a high risk for breast cancer.
Genetic testing in India: In women with a significant family history of breast cancer, a specialist surgeon may be needed to be consulted for the statistical assessment of one’s individual breast cancer risk. A pretest genetic counseling is mandatory before a DNA testing. All issues including the implications of a positive test, the implications of a negative test, the limitations of the testing, the options for risk estimation without the genetic testing, the risk of passing a mutation to children, the technical accuracy of the test, the cost of the testing, the risk of psychological distress, the risk of discrimination and the options and the limitations of medical surveillance and screening following the testing should be clearly discussed. The genetic testing should be only done when there is a strong contribution of a hereditary component if it is suggested by the family history. The test should not be done without the availability of adequate pretest and “post-test” counseling. Cancer surveillance should begin at an early age because there is a high risk for cancer in the younger age groups. Breast cancer surveillance is done by breast self examination (18 years), an annual clinical examination and mammography annually or semiannually, beginning at the age of 25 years. A prophylactic mastectomy can be offered as mastectomy has been shown to cause a 90% reduction in the incidence of cancer in the mutation carriers and an 80% reduction in the cancer related deaths (20). The mammographic screening for breast cancer may not be costeffective in India at present, but regular Breast Self Examination (BSE) needs to be promoted for the early detection of breast cancer. Breast Self Examination can be propagated through print and electronic media, as well as through health care personnel in various settings. The measures which have been identified and propagated for cancer control in the developed countries may not be applicable in the Indian context. We have to find answers to our problems through methods which are feasible and evaluable in the Indian context.
Social issues: While talking about breast cancer, one should also consider the social issues which are related to this. Women who have been diagnosed with breast cancer face a range of issues that differs greatly from those which older and younger women face. Some older women may avoid any kind of treatment because of the fear of the “side-effects” that accompany some therapies, while some may want to take the most aggressive treatment which is available. Another top issue which some women face is the worry about finances. While already struggling with her health, a woman must then wade into the complicated waters of payments and treatment costs. The problem will become profound and significant if the woman is a widow or if her children are not staying with her and she may lack adequate support.
Stigma:One of the major barriers in the diagnosis and treatment of breast cancer is the social stigma. In Western countries, the stigma is somewhat subtle, but it still exists. But in a country like India, cancer is still considered as a death sentence. Because the general belief is that cancer is untreatable, no matter how much treatment is received and even if the disease has a good prognosis, the society will cast out the cancer sufferers. So, a woman who is diagnosed with breast cancer may beat the cancer and survive, but at what cost? Patients of breast cancer experience great stress during the treatment. The social stigma which is associated with breast cancer and the potential disfigurement of mastectomy pose obstacles in the care of the patients. Thus, even in modern cultures, with the latest technologies and treatments at hand, women and men with breast cancer may feel stigmatized - set apart and marked as too different - leading some of them to feel more victimized by the society than by the disease. Unfortunately, it is the society’s loss that breast cancer has got such stigma.
Awareness: As India is rapidly stepping into urbanization, westernization, resulting in a change in the lifestyle, significantly contributes to the increased burden of breast cancer in the country. A late stage at presentation is the main reason for the poor survival of the cancer patients in India. The late presentation is mainly due to the lack of diagnostic facilities at the peripheral levels and the lack of awareness about breast cancer. So, there is a need to increase the public awareness regarding the prevention, early diagnosis and the treatment which is available for breast cancer. A pink ribbon is the breast cancer awareness symbol. October is the breast cancer awareness month. A public awareness is made by educating the population about the risk factors, and through screening by physical examination or by Breast Self Examination. The strategy which is adopted by the Tata Memorial Centre’s Rural Cancer Project at Barshi in India is aimed at educating the population and at motivating the people to undergo medical investigations. The FBCP (Forum for Breast Cancer Protection) is a non-government organization which is focused on spreading breast cancer awareness. Medical professionals from institutes and hospitals like AIIMS , Sir Ganga Ram Hospital and Rajiv Gandhi Cancer Institute joined together to start FBCP in 2001. So, by making people aware about the details of breast cancer, we can certainly make a positive change in the present picture of breast cancer in India.


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DOI: JCDR/2012/3802:1985


Date of Submission: Dec 09, 2011
Date of Peer Review: Jan 15, 2012
Date of Acceptance: Feb 21, 2012
Date of Publishing: May 01, 2012

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