Superoxide Dismutase (rs2070424, rs4880, rs2536512) and Catalase (rs794316, rs1001179) SNPs and their Association with Breast Cancer Risk: Findings from a Hospital Based Case-Control Study.

BACKGROUND: The antioxidant enzymes are important cellular components involved in detoxification of reactive oxygen species (ROS) and protect cells from ROS induced oxidative damage. Single nucleotide polymorphisms (SNPs) of antioxidant enzyme coding genes such as superoxide dismutase (SOD) and catalase (CAT) may alter the enzyme activity which can influence susceptibility towards carcinogenesis.  Therefore, the present study was planned to investigate possible SNPs of SOD (SOD1 (Cu,Zn-SOD), SOD2(Mn-SOD), SOD3(EC-SOD) and CAT genes and their possible association with breast cancer risk in rural Indian women. METHODS: In this case-control study, the association of SOD and CAT gene polymorphism was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The study was conducted among 400 clinically breast cancer patients and 400 healthy women in a population of South-Western Maharashtra. The logistic regression analysis was carried out to calculate Odds ratio (OR) with 95% confidence interval and p-value, where p ≤0.05 was considered as statistically significant. RESULTS: The results of analysis of genotype frequency distribution showed significant association of rs4880 SNP of Mn-SOD with BC risk at homozygous variant (CC/CC) genotype (OR 2.46; 95%CI, 1.61-3.75; p<0.0001) and corresponding frequency of variant (C) allele (OR 1.53; 95%CI, 1.25-1.86; p<0.0001). In CAT gene polymorphisms the variant (T/T) was increased significantly in BC cases as compared to controls (OR 3.45; 95%CI, 2.17-5.50; p<0.0001) along with its variant (T) allele (OR 2.01; 95%CI, 1.63-2.48; p<0.0001). CONCLUSIONS: The results implied that, C/C genotype of SOD2-1183T/C polymorphism and T/T genotype of CAT-262 C/T polymorphism may be associated with an increased breast cancer risk. However, SOD1-251 A/G and SOD3-172 G/A polymorphisms did not show any significant difference in variant homozygous genotypes of patients compared to controls.

Genetic Polymorphisms of XPC, XPD, XPG Genes and their Association with Radiotherapy Induced Toxicity among Head and Neck Cancer Patients: A Hospital Based Study from Maharashtra.

BACKGROUND: The present study was planned to investigate possible association of single nucleotide polymorphisms (SNPs) of nucleotide excision repair (NER) genes such as XPC, XPD, XPG with acute radiation induced toxicities such as skin reactions and oral mucositis in normal tissue from head and neck cancer (HNC) patients receiving radiotherapy.  Methods: Two hundred and fifty HNC patients receiving radiotherapy were enrolled in this study and the acute toxicity reactions and radiation response were recorded. Association of SNPs rs2228001 of XPC, rs238406, rs13181 of XPD and rs17655 of XPG gene with normal tissue reactions in the form of dermatitis and mucositis were studied by PCR-RFLP and direct DNA sequencing. RESULTS: The results of univariate analysis of SNPs of XPC, XPD and XPG showed that XPC polymorphism at codon 939 of exon 15 (A>C) was not associated with dermatitis (OR=0.30, 95% CI: 0.06-1.39; p=0.125), or oral mucositis (OR=1.14, 95% CI: 0.41-3.20; p=0.793). The XPD codon 156 of exon 6 (C>A) and codon 751 of exon-23 A>C) polymorphism showed no association with radiosensitivity in HNC patients (OR=1.50, 95% CI: 0.60-3.71; p=0.080) for dermatitis, (OR=1.54, 95% CI: 0.66-3.61; p=0.312) for oral mucositis. The 1104 Asp variant genotype or allele of XPG (OR=1.35 95% CI: 0.50-3.64; p=0.541) showed no association with degree of radiotherapy associated dermatitis or mucositis (OR=0.80, 95% CI: 0.32-2.03; p=0.648) in HNC patients. The variant C allele of 2920 A/C genotype of XPC gene at codon 939 of exon 15, found protective with developing skin reactions with grade >1 (OR=0.60, 95% CI: 0.36-0.97; p=0.039) in HNC patients treated with radiotherapy. CONCLUSION: The results obtained in this study concluded that the SNPs rs2228001of XPC, rs238406, rs13181 SNPs of XPD and rs17655 SNP of XPG are not associated with normal tissue toxicity in HNC patients treated with radiotherapy. Radiotherapy with high radiation dose was significantly associated with oral mucositis in response to radiotherapy.

Single Nucleotide Polymorphisms in DNA Repair Genes (XRCC1, XRCC2, XRCC3) and Their Association with Radiotherapy Toxicity among Head and Neck Cancer Patients:A Study from South-Western Maharashtra.

BACKGROUND: The genetic polymorphisms in DNA repair genes and their correlation with normal tissue toxicity in response to radiation therapy has not been consistently proven in many of the studies done in head and neck cancers (HNC). This study was intended to investigate the association of most common single nucleotide polymorphisms of DNA repair genes with acute radiation induced toxicities such as skin reactions and oral mucositis in normal tissue from HNC patients receiving radiotherapy from South-Western Maharashtra. METHODS: Two hundred HNC patients receiving radiotherapy were enrolled in this study and the radiation injuries in the form of skin reactions and oral mucositis were recorded. Three single nucleotide polymorphisms (SNPs) rs1799782, rs25489) rs25487 of XRCC1 gene, rs3218536in XRCC2 gene and rs861539 SNP of XRCC3 gene were studied by PCR-RFLP and direct DNA sequencing.  Results: The univariate analysis of SNPs of XRCC1, XRCC2 and XRCC3, the obtained results verified that XRCC1 polymorphism at 194Trp of exon 6 (OR=0.69, 95% CI: 0.28-1.71; p=0.433), codon 280 at exon 9 ((OR=1.05, 95% CI: 0.42-2.63; p=0.911) and codon 399 of at exon 10(OR=1.06, 95% CI: 0.52-2.15; p=0.867) and XRCC2 polymorphism at codon 188 at exon 3 (OR=1.07, 95% CI: 0.46-2.47; p=0.866) and 241Met variant genotype of XRCC3 (OR=2.63 95% CI: 0.42-16.30; p=0.298) showed no association with degree of radiotherapy associated dermatitis or mucositis in HNC patients. CONCLUSION: The findings from this study postulated that none of rs1799782, rs25489, rs25487 SNPs of XRCC1, rs3218536 SNP of XRCC2 nor rs861539 SNP of XRCC3 were associated with increased toxicity of radiotherapy in HNC patients of south-western Maharashtra. 
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Impact of Interaction between Single Nucleotide Polymorphism of XRCC1, XRCC2, XRCC3 with Tumor Suppressor Tp53 Gene Increases Risk of Breast Cancer: A Hospital Based Case-Control Study.

BACKGROUND: At present very little information is available on combined effects of DNA repair genes with tumor suppressor gene polymorphisms and their association with cancer susceptibility. No such association studies have been carried out with breast cancer or any other cancer from India. Present study was conducted to study the combined effects of SNPs of XRCC1, XRCC2, XRCC3 with Arg72Pro and Arg249Ser SNPs of TP53 gene in risk of BC in rural parts of India. METHODS: The polymorphisms of Arg194Trp, Arg280His, Arg399Gln of XRCC1, Arg188His of XRCC2 and Thr241Met of  XRCC3 with Arg72Pro and Arg249Ser of TP53 gene polymorphisms was studied by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. The association among the polymorphisms with breast cancer risk was studied by Odds ratio within 95% confidence interval and SNP-SNP interaction were confirmed by logistic regression analysis. RESULTS: The results of genotype frequency distribution of XRCC1, XRCC2, XRCC3 genotypes showed positive association between XRCC1 Arg280His polymorphism and BC risk (OR=4.54; 95% CI: 3.36- 6.15; p<0.0001).  Also the heterozygous genotypes Arg188His of XRCC2 (OR=1.58; 95% CI: 1.13- 2.21; p=0.007) and Thr241Met genotype of XRCC3 (OR=2.13; 95% CI: 1.44- 3.13; p=0.0001) were associated with BC risk. The combination of heterozygous Arg280His genotype of XRCC1 along with Arg72Pro genotype of TP53 increased the risk of BC (OR=4.53; 95% CI: 2.85-7.20); p<0.0001). Similarly,  the combined effect of heterozygous Arg/His genotype of XRCC1 with heterozygous Arg/Ser genotype of TP53 at codon 249 showed significant association with increased BC risk (OR=5.08; 95% CI: 2.86-9.04); p<0.0001). CONCLUSION: The findings derived from our study concluded that the heterozygous variant Arg280His genotype of XRCC1 and Thr241Met polymorphism of XRCC3 in combination with heterozygous arginine72proline genotype and heterozygous Arg249Ser polymorphism of TP53 showed significant association with breast cancer risk in Maharashtrian women.

Assessment of Intratumoural and Stromal Infiltrating Lymphocytes In The Various Subtypes of Breast Carcinoma Patients who have Received Neoadjuvant Chemotherapy.

BACKGROUND: Breast cancer comprises a highly heterogeneous subset of tumours that respond well to Neoadjuvant Chemotherapy (NAC). Tumour Infiltrating Lymphocytes (TIL) act as a means to an end by shedding light on the treatment response as well as predictive factors to the clinicopathological features for the same. Therefore, this article attempts to shift the attention to the relevance of TIL in the aforementioned aspects by bringing to notice the contrasting traits displayed by them in the different immunohistochemical subtypes of breast carcinoma. MATERIALS AND METHODS: 75 triple-negative breast cancer (TNBC) patients, 25 human epidermal growth factor receptor (HER2BC) positive patients and 77 hormone receptor (HRBC) positive breast cancer patients were included in this study who received NAC before surgical excision of the tumour which was then stained using routine Haematoxylin and Eosin techniques. Standardised guidelines were used to evaluate TIL in the stroma and the tumour. RESULTS: In TNBC, a significant association between Intratumoural (IT) TIL (p=0.0288) and Intrastromal (IS) TIL (p=0.0250) with pathological complete response (pCR). IS TIL and age at operation (p=0.0494) showed significant values but no correlation was found with IT TIL. In HER2BC, IS TIL revealed a significant association with the tumour response(p=0.0229). A strong association was found between IT TIL and the age of menopause(p=0.0441). In HRBC, no significant associations were found between IT and IS TIL scores and the clinicopathological features. CONCLUSION: The predictive factors of TIL and complete response post-neoadjuvant chemotherapy can be a strong indicative factor for immunohistochemical markers. It also helps throw light on further studies which can be carried out to determine the clinicopathological features and TIL correlation in the various subtypes of breast carcinoma.

TP53 (rs1042522, rs28934571) and TP21 (rs1801270, rs1059234) Polymorphisms and Risk of Breast Cancer among Rural Women of Maharashtra: Findings from a Hospital Based Case- Control Study.

BACKGROUND: Various studies all around the world depicted the relationship of polymorphisms in tumor suppressor genes with risk of various cancers, but there are unambiguous conclusions on this association. A hospital based case-control study was designed to review the association of polymorphism of tumor suppressor genes p21 and p53 with breast cancer risk in women residing in rural Maharashtra. METHODS: Two single nucleotide polymorphisms (SNPs) a C>A transversion (Ser>Arg) at codon 31 of exon 2 (rs1801270), C>T transition occurring 20bp upstream from stop codon of exon 3 (rs1059234) in p21 gene and G>C (Arg>Pro) transition at codon 72 of exon 4 (rs1042522), G>T (Arg>Ser) transition at codon 249 in exon 7 (rs28934571) in p53 gene were studied. To precise the quantitative assessment, we enrolled 800 subjects sorted into 400 clinically confirmed breast cancer patients and 400 healthy women from a tertiary care hospital (Krishna Hospital and Medical Research Centre) of south-western Maharashtra. The genetic polymorphisms in p21 and p53 genes was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using blood genomic DNA isolated from breast cancer patients and controls.  The level of association of polymorphisms was assessed using Odds ratio (OR) with 95% confidence interval and p-value identified using logistic regression model. RESULTS: After the analysis of SNPs (rs1801270, rs1059234) of p21 and (rs1042522, rs28934571) in p53 gene our analysis suggested that heterozygote Ser/Arg genotype with OR=0.66; 95% CI: 0.47- 0.91; p=0.0003 and homozygote variant Arg/Arg genotype with OR=0.23; 95% CI: 0.13- 0.40; p<0.0001of rs1801270 of p21 was negatively associated with risk of breast cancer in studied population. CONCLUSION: The findings from this study supported that rs1801270 SNP of p21 was inversely associated with breast cancer risk in the studied rural women population.

Evaluation and comparison of intratumoural and intrastromal infiltrating lymphocytes with clinicopathological features in breast carcinoma patients who have received neoadjuvant chemotherapy - A cross-sectional study.

Background: The microenvironment of breast cancer plays a significant role in determining the prognosis of the disease. With the shifting paradigm on the predictive factors post-Neoadjuvant Chemotherapy (NAC), it was sought out that Tumour infiltrating lymphocytes (TILs) are of valuable use for the same. Yet, the delineation of the two types - Intrastromal and Intratumoural has seldom been facilitated. This study, therefore, aimed to evaluate, analyse and compare the two - to gauge the importance of the treatment outcome and clinicopathological features. Materials and methods: 180 breast cancer patients were included in this study who underwent NAC, and their post-surgically resected tumour specimens were sectioned and stained using routine Haematoxylin and Eosin techniques. The evaluation of TILs in the stroma and tumour was done based on the standardised guidelines. Results: Out of the 180 patients, 55 (i.e. 30.56%) displayed pathological complete resolution (pCR). Furthermore, Intratumoural TILs had a slight association with the pCR (p = 0.0335) whereas Intrastromal TILs had a significantly large association with pCR (p < 0.0001) dependent on the lymphocytic response. Backward regression revealed that - the age at operation, pCR, lymph node involvement and menopause highly contributed to predicting 68.2% of the total cases correctly with a sensitivity of 93.0% and specificity of 24.6% for Intratumoral TILs. Age at operation, pCR, lymph node involvement and tumour emboli highly contributed to predicting 71.5% of the total cases correctly with sensitivity of 71.6% and specificity of 71.4% for Intrastromal TILs. Conclusion: TILs and the prediction of NAC and pCR should be made standardised and reproducible so that they can be universally available to all patients with breast cancer. Through this study, further avenues of research have opened up for their relations with clinicopathological features mainly age at operation and menopausal status.

Multicentric Metaplastic Breast Carcinoma with Squamous Differentiation.

Metaplastic breast carcinoma is a rare primary breast malignancy. A 45-year-old female patient presented with multicentric lumps in left breast of 6 months duration and history of axillary lymphadenopathy of 2 months duration. Mammography revealed two high density masses with ill defined margins. Fine needle aspiration cytology was positive for duct carcinoma cells. Histo pathologic examination, reported as "Multicentric infiltrating duct carcinoma with squamous differentiation left breast", grade 2. Immunohistochemistry revealed negativity for ER, PR and positivity for HER-2/neu. We are presenting this rare case for clinical, radiological, histopathological and immunohistochemical study.

Apocrine carcinoma of breast: a case report with review of the literature.

Apocrine carcinoma is a very rare form of breast malignancy with an incidence of <1% of female invasive breast carcinoma. We report a case of apocrine carcinoma in a 42-year female with marked adenosis showing apocrine metaplasia and discuss the criteria to diagnose apocrine carcinoma with the emerging concept of androgen receptor positivity with its implication on treatment and management of the patient.

Rhabdomyosarcoma of the breast - a rare malignancy.

PATIENT: Female, 60 FINAL DIAGNOSIS: Rhabdomyosarcoma of the breast Symptoms: Lump in axilla Medication: - Clinical Procedure: Mastectomy Specialty: Oncology. OBJECTIVE: Rare disease. BACKGROUND: Primary nonepithelial malignancies of the breast include primary breast sarcomas, therapy-related breast sarcomas, the phyllodes tumors, and primary breast lymphomas. They account for less than 5% of all breast neoplasms. CASE REPORT: We report the case of a 60-year-old postmenopausal female diagnosed with rhabdomyosarcoma with infiltrating duct carcinoma. She was treated with modified radical mastectomy with axillary clearance and postoperative chemotherapy. CONCLUSIONS: Primary rhabdomyosarcoma of the breast in adults is extremely rare. Rhabdomyosarcomas in adults account for less than 3% of all adult primary soft-tissue sarcomas. Primary breast sarcomas usually present as large painless breast lumps with no associated skin and nipple changes or axillary lymphadenopathy; they are more aggressive and have more rapid growth than epithelial malignancies or benign breast lesions. The tumor can grow to large size, around 5.8 cm. Affected patients are typically women in their 50 s (ranging from 17 to 89 years), but it is also seen in men. The treatment of primary breast sarcomas requires a multidisciplinary approach. Surgery remains the mainstay of therapy. Chemotherapy has no clearly defined role in primary breast or soft-tissue sarcomas. The prognosis of primary breast sarcomas depends on the histologic grade and size of the tumor. They spread locally and hematogenously, but they are not usually associated with axillary lymphadenopathy.

Matrix-producing metaplastic breast carcinoma - a rare malignancy.

Patient: Female, 33 Final Diagnosis: Matrix-producing metaplastic breast carcinoma Symptoms: - Medication: - Clinical Procedure: Operative Specialty: Oncology Objective: Rare disease. BACKGROUND: Metaplastic breast carcinomas are ductal carcinomas that undergo metaplasia into non-glandular growth patterns. They are very rare, accounting for less than 1% of all invasive breast carcinomas. CASE REPORT: A 33-year-old female patient presented with a lump in her left breast. Axillary lymph nodes were not palpable. FNAC of the lump was positive for malignant cells. The patient underwent modified radical mastectomy with axillary clearance. The histopathological report was matrix-producing carcinoma with infiltrating duct carcinoma. The tumor was positive for immunohistochemical markers keratin, EMA (Epithelial Membrane Antigen), and S100, thus confirming it to be matrix-producing carcinoma breast. After surgery, the patient recovered uneventfully. CONCLUSIONS: Matrix-producing breast carcinoma is a rare type of metaplastic carcinoma characterized by a ductal carcinomatous element with direct extension to areas showing cartilaginous or osseous differentiation, lacking an interspersed spindle cell component. It has better prognosis than metaplastic carcinoma. Immunohistochemically, they are positive for keratin, EMA (Epithelial Membrane Antigen), and S100. The tumor, which is matrix-producing, is S100 reactive and nonreactive for cytokeratin. They are usually ER- and PR-negative. The average age of these patients is approximately 58 years. Surgery remains the mainstay of therapy, using either mastectomy or local excision.