CAG and GGN Repeat Length Polymorphisms of Androgen Receptor Gene in Women with Breast Cancer: A Case-Control Study from South India

Durgadatta Tosh,Vishnupriya Satti,Lakshmi Rao,Lalji Singh,Arvind Babu,Tipirisetti Nageswar Rao,Bineet Panda,Digumarti Raghnadharao

doi:10.4236/jct.2012.325093

Abstract

Aim: The Androgen Receptor (AR) is a ligand-dependent transcriptional activator and the AR gene contains a highly polymorphic trinucleotide repeat CAG and GGN in the first exon. Given the lack of information AR-CAG and GGN repeat polymorphism and its potential correlation with breast cancer in South Indian women, we conducted a case-control study to observe the effects of CAG & GGN repeat length polymorphism and risk of breast cancer. Methods: Polymorphisms for AR-CAG and GGN repeat length was detected by Gene Scan analysis in the genomic DNA from cases with breast cancer and controls. Results: Association between AR genotype was calculated by categorising alleles as short (S) and long (L) and taking median value as the cut-off. LL genotype of CAG repeat was found to be associated with breast cancer (OR, 4.58; 95% CI, 10.61-1.98; p—0.0004). GGN repeat having ≥21 was found in most of the cases and none of the cases showed 20 repeats thus indicate that alleles having homozygous repeat 20 may be protective towards breast cancer. Also, SS genotype was observed in 56.84% of cases and in 73.03% of controls (OR, 0.48; 95% CI, 0.26-0.89; p value, 0.02). Conclusion: Our results indicate that longer CAG and GGN repeat may be associated with breast cancer whereas, the shorter GGN repeat length genotype of AR are protective.

Highlights

Breast cancer is the most common cancer and the leading cause of the cancer deaths in women today
Our results indicate that longer CAG and GGN repeat may be associated with breast cancer whereas, the shorter GGN repeat length genotype of Androgen Receptor (AR) are protective
Gene Scan was done for the two-microsatellite regions of AR gene i.e. CAG and GGN repeats in all the cases and controls

Summary

Introduction

Breast cancer is the most common cancer and the leading cause of the cancer deaths in women today. The incidence of breast cancer varies greatly around the world: it is lowest in less-developed countries, greatest in the more-developed countries and is on the rise especially in developing countries such as India. A recent data showed that India has one of the highest cancer rates in the world [1]. The incidence of breast cancer in India is on the rise and is rapidly becoming the number one cancer in women, pushing the cervical cancer to the second spot. Exposures to endogenous and exogenous hormones are known to influence breast cancer risk. The predominant sex steroid hormones in postmenopausal women, act through the androgen receptor (AR), a member of the steroid receptor subfamily.

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