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Contribution of XPD (Lys751Gln) and XRCC1 (Arg399Gln) Polymorphisms in Familial and Sporadic Breast Cancer Predisposition and Survival: An Indian Report

  • Original Paper
  • Published:
Pathology & Oncology Research

Abstract

The etiology of a significant proportion of familial breast cancers is still poorly understood, with known high penetrance gene mutations accounting for only a small proportion of the cases. The increased risk of breast cancer for the majority of women with a family history likely reflects shared minor low penetrant genetic factors. In the present case-control study undertaken to examine the influence of DNA damage repair gene polymorphisms in familial and sporadic breast cancer susceptibility, 219 Sporadic and 140 familial breast cancer patients and 367 controls were genotyped using PCRRFLP. Odds Ratios (ORs) and 95% Confidence Intervals (95%CIs) were calculated by unconditional logistic regression adjusted to age. Variant genotypes XRCC1 Arg/Gln or Gln/Gln and XPD Lys/Gln or Gln/Gln increased both familial and sporadic breast cancer susceptibility. However, when the intra group risk was compared, the risk due to the XPD polymorphic genotypes Lys/Gln or Gln/Gln was significantly lower among familial breast cancer patients compared to sporadic breast cancer patients [OR = 0.61; 95%CI = 0.39–0.94; p value = 0.024) whereas the risk implied by XRCC1 variant genotype was not significantly different between the familial and nonfamilial groups of breast cancer patients [OR = 0.97; 95%CI = 0.63–1.49; p value = 0.882]. Both these variant genotypes were not associated with the disease characteristics or survival of either familial or sporadic breast cancer patients. This study represents an addition to previous published work on GSTs from the same study population and substantiates the hypothesis that the impact of the low penetrance gene polymorphisms differ by family history of the disease.

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Abbreviations

BRCA1:

breast cancer 1

BRCA2:

breast cancer 2

XRCC1:

X-ray repair cross-complementing group 1

XPD:

xeroderma pigmentosum group D

SNPs:

single nucleotide polymorphisms

PCR-RFLP:

polymerase chain reaction-restriction fragment length polymorphism

OR:

odds ratio

95%CI:

95% confidence interval

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Acknowledgements

We are grateful to the participants of the study and their families without whose cooperation this study would not have been possible. We also thank the staff of various departments of Regional Cancer Centre, Thiruvananthapuram for their help in identification of patients and providing necessary data for the study.

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Authors and Affiliations

  1. Division of Cancer Research, Regional Cancer Centre, Trivandrum, 695 011, Kerala, India

    Volga S. Syamala, Vani Syamala, Hariharan Sreedharan, Praveenkumar B. Raveendran & Ravindran Ankathil

  2. Division of Radiation Oncology, Regional Cancer Centre, Thiruvananthapuram, 695011, Kerala, South India

    Ratheesan Kuttan

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  1. Volga S. Syamala
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Correspondence to Ravindran Ankathil.

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Syamala, V.S., Syamala, V., Sreedharan, H. et al. Contribution of XPD (Lys751Gln) and XRCC1 (Arg399Gln) Polymorphisms in Familial and Sporadic Breast Cancer Predisposition and Survival: An Indian Report. Pathol. Oncol. Res. 15, 389–397 (2009). https://doi.org/10.1007/s12253-008-9135-8

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