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Original Article
124 (
3
); 305-312
doi:
10.25259/IJMR_20061243_305

HLA alleles in pre-menopausal breast cancer patients from western India

Cancer Research Institute, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Khraghar, Navi Mumbai, India
HLA Testing Laboratory, Department of Transfusion Medicine & Tata Memorial Centre, Mumbai, India
Department of Surgical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India
Present address: Reliance Life Sciences, Dhirubhai Ambani Life Sciences Centre, Molecular & Genetic Diagnostics R-282, TTC Area MIDC, Rabale, Navi Mumbai 400701, India

Reprint requests: Dr N. Joshi, Cancer Research Institute, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Khraghar, Navi Mumbai 410208, India e-mail: njoshi@actrec.gov.in

Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background & objectives:

Cytotoxic function of Natural Killer (NK) cells is regulated by the products of HLA class I genes. Associations between HLA alleles and risk for cancers have been suggestedearlier. Several reports further emphasize the need to examine influence of HLA genotypes on risk for malignant disorders. Therefore, we undertook this study to assess the possibility of association of HLA-class I alleles in pre-menopausal breast cancer patients.

Methods:

Eighty one pre-menopausal breast cancer patients and 160, age and ethnicity matched healthy women from western India were studied. Genotyping for HLA class I alleles and HLAB* 40 alleles (high resolution) was performed using genotyping kits from Genovision Inc., USA.

Results:

Nearly two-fold higher frequency of HLA – B*40 (16%) was observed in patients compared to controls (O.R. = 2.2; 95% C.I.-1.15-4.34; P<0.02). High resolution typing for HLA-B*40 alleles revealed predominance of HLA-B*4006 allele in both the study groups. Two other important observations relate to lower frequency of HLA - B*08 in patients and homozygosity at HLA-Cw locus in significantly higher proportion of patients.

Interpretation & conclusion:

The nature of peptides presented by HLA-B*4006 may have implications for higher frequency of HLA-B*40 in breast cancer patients. Higher frequency of homozygosity at HLA-Cw alleles in patients suggests a role for killer immunoglobulin-like receptors (KIRs) in NK cell mediated immune surveillance. Results of this study provide directions to further analyse role of immunogenetic mechanisms governing innate and adaptive immune responses contributing to modulation of risk for breast cancer.

Keywords

Breast cancer
haplotype frequencies
HLA-B* 40
HLA-class I allele
linkage disequilibrium

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