Absence of 185delAG and 6174delT Mutations among Breast Cancer Patients of Eastern India.

Abhijit Chakraborty,Jayasri Basak,Ashis Mukhopadhyay,Debolina Banerjee

doi:10.7314/apjcp.2015.16.17.7929

Abstract

The incidence of breast cancer in India is on the rise and is rapidly becoming the number one cancer in females, pushing the cervical cancer to the second position. Most of the predisposition to hereditary breast and ovarian cancer has been attributed to inherited defects in two tumor suppressor genes BRCA1 and BRCA2. Alterations in these genes have been reported in different populations, some of which are population- specific mutations showing founder effects. Two specific mutations in the BRCA1 (185delAG) and BRCA2 (6174delT) genes have been reported to be of high prevalence in different populations. The aim of this study was to estimate the carrier frequency of 185delAG and 6174delT mutations in eastern Indian breast cancer patients. We selected 231 histologically confirmed breast cancer patients from our tertiary cancer care center in eastern India. Family history was obtained by interview or a self-reported questionnaire. The presence of the mutation was investigated by allele specific duplex/multiplex-PCR on genomic DNA extracted from peripheral blood. A total of 231 patients (age range: 26-77 years), 130 with a family history and 101 without were screened. The two founder mutations 185delAG in BRCA1 and 6174delT in BRCA2 were not found in any of the subjects. This was confirmed by molecular analysis. Our findings suggest that these BRCA mutations may not have a strong recurrent effect on breast cancer among the eastern Indian population. The contribution of these founder mutations to breast cancer incidence is probably low and could be limited to specific subgroups. This may be particularly useful in establishing further pre-screening strategies.

Highlights

Breast cancer (BC) is a form of cancer in the glandular breast tissue
Our findings suggest that these BRCA mutations may not have a strong recurrent effect on breast cancer among the eastern Indian population
A study conducted in breast and ovarian cancer families and sporadic breast cancer patients of Indian origin revealed 185delAG mutation in patients with family history of breast cancer and no mutation was found in sporadic cases (Kumar et al, 2002)

Summary

Introduction

Breast cancer (BC) is a form of cancer in the glandular breast tissue. In India, women diagnosed with carcinoma of the breast is on an average of 80,000 and women die of this disease every year is 40,000, and it is marked as the second most common cancer among Indian women (19%) after cervical cancer (30%) (Saxena et al 2006). The prevalence of BRCA mutations in asian breast cancer patients is similar in range to that of other ethnic populations (Haeyoung et al, 2013) In this group, 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 are the three most frequently found mutations, and more than 12% of the women who develop breast cancer bear one of these mutations (King et al, 2003, Haytural et al 2013). Most of the predisposition to hereditary breast and ovarian cancer has been attributed to inherited defects in two tumor suppressor genes BRCA1 and BRCA2 Alterations in these genes have been reported in different populations, some of which are populationspecific mutations showing founder effects. Conclusions: Our findings suggest that these BRCA mutations may not have a strong recurrent effect on breast cancer among the eastern Indian population The contribution of these founder mutations to breast cancer incidence is probably low and could be limited to specific subgroups. This may be useful in establishing further pre-screening strategies

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Conclusion