Epidemiological factors, genetic and inflammatory markers in the development of Breast Cancer in Malwa region of Punjab
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Date
2019
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Central University of Punjab
Abstract
Breast cancer is one of the most common malignancy among women and also the leading cause of death worldwide. Malwa region of Punjab is reported to have the highest number of cancer cases in comparison with the other two regions (Doaba and Majha). The cancer prevalence in this region was reported to be 1089 per million/year in 2013 (with around 35.7% breast cancer cases), as per the Department of Health and Family Welfare. The aim of present study was to carry out a systematic epidemiological study, explore the contribution of mutations in breast cancer susceptibility genes, and gene-gene interactions in the development of breast cancer in Malwa region of Punjab. In addition, exome sequencing of the male breast cancer patients was carried out to identify the specific genetic alterations associated with the disease in this region. Inflammatory markers (cytokines and C-reactive protein levels) and albumin levels were also estimated to evaluate their association with the development of the disease and outcome including death, recurrence, and metastasis. Three hundred breast cancer patients (Female:Male = 296:4) were recruited from Guru Gobind Singh Medical College & Hospital, Faridkot and Max Hospital, Bathinda. Equal number of age and sex matched controls were also recruited from the same demographic area with the help of Rural Medical Officers. The study was approved by the ethics committee of the Central University of Punjab. The information regarding the demographic profile was collected in a structured questionnaire. The blood samples were collected with the written informed consent of the patients. DNA isolation was carried out by phenol:chloroform method. The genotyping was performed by global screening array (GSA; Illumina Infinium HD), exome sequencing and PCRRFLP. The levels of inflammatory markers and albumin were estimated by using BD Accuri flow cytometer and ERBA 200 bioautoanlyzer. The association of demographic features with the disease was evaluated by Student’s t-test. Mann-Whitney test was used to evaluate the association of CRP, cytokines and albumin with the outcome. Softwares including R/Bioconductor and OpenEpi were used to evaluate the association of pathogenic alterations with the disease. The influence of novel mutations on protein structure was examined by molecular dynamics simulations. Follow-up of the patients was carried out with the help of clinicians. Infiltrating breast cancer was the most common type of breast cancer in patients. Triple negative breast cancer was observed in 17.5% of patients. All the patients underwent modified radical mastectomy and lumpectomy. The breast cancer patients v carried mono/biallelic alteration in 15 breast cancer susceptibility genes including ATM, BRCA2, STK11, PTEN, BRIP1, CHEK2, RAD51C, NBN, MLH1, MSH2, MSH6, MUTYH, CDK2NA, CYTB and MTHFR as per the results of GSA. Familial cases of breast cancer were found to carry alterations in ATM, BRCA2, STK11, PTEN, BRIP1, CHEK2, RAD51C, NBN, MLH1, MSH2, MSH6, MUTYH, CDK2NA, CYTB and MTHFR genes. Novel pathogenic variants in PALB2, STK11, CHEK2, BRCA2, BARD1, BRIP1, NF2, and FZR1 genes were detected in male breast cancer patients. These were found to alter the specific protein structure. Among the inflammatory markers CRP, IL-6 & IL17A were found to be significantly associated with poor outcome in the patients. High levels of albumin were also found to be associated with increased overall survival. In conclusion, results of this study can guide to develop a panel to test the breast cancer patients for pathogenic mutations from Malwa region of Punjab. The present study suggests that the screening of BRCA2, MSH2, and MLH1 should be carried out in general population since previous studies have reported that these mutations increase the risk of breast cancer by 10-fold and accordingly evidence-based management recommendations can be given to the individuals bearing these mutations. Familial breast cancer patients need to be screened for BRAD1, MSH2, MLH1, BRCA2 and CYTB genes since these alterations were observed in familial breast cancer patients. IL-6, IL-17A, CRP, and albumin can be used as prognostic markers for breast cancer in Malwa region of Punjab.
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Keywords
Breast cancer, gene-gene interactions, cytokines, inflammatory markers
Citation
Kaur, Raman Preet & Munshi, Anjana (2019) Epidemiological factors, genetic and inflammatory markers in the development of Breast Cancer in Malwa region of Punjab