Contribution of germline BRCA1 and BRCA2 sequence alterations to breast cancer in Northern India

BACKGROUND: A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Indian women. We investigated the distribution and the nature of BRCA1 and BRCA2 germline mutations and polymorphisms in a cohort of 204 Indian breast cancer patients and 140 age-matched controls. METHOD: Cases were selected with regard to early onset disease (≤40 years) and family history of breast and ovarian cancer. Two hundred four breast cancer cases along with 140 age-matched controls were analyzed for mutations. All coding regions and exon-intron boundaries of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis followed by direct sequencing of detected variants. RESULTS: In total, 18 genetic alterations were identified. Three deleterious frame-shift mutations (185delAG in exon 2; 4184del4 and 3596del4 in exon 11) were identified in BRCA1, along with one missense mutation (K1667R), one 5'UTR alteration (22C>G), three intronic variants (IVS10-12delG, IVS13+2T>C, IVS7+38T>C) and one silent substitution (5154C>T). Similarly three pathogenic protein-truncating mutations (6376insAA in exon 11, 8576insC in exon19, and 9999delA in exon 27) along with one missense mutation (A2951T), four intronic alterations (IVS2+90T>A, IVS7+75A>T, IVS8+56C>T, IVS25+58insG) and one silent substitution (1593A>G) were identified in BRCA2. Four previously reported polymorphisms (K1183R, S1613G, and M1652I in BRCA1, and 7470A>G in BRCA2) were detected in both controls and breast cancer patients. Rare BRCA1/2 sequence alterations were observed in 15 out of 105 (14.2%) early-onset cases without family history and 11.7% (4/34) breast cancer cases with family history. Of these, six were pathogenic protein truncating mutations. In addition, several variants of uncertain clinical significance were identified. Among these are two missense variants, one alteration of a consensus splice donor sequence, and a variant that potentially disrupts translational initiation. CONCLUSION: BRCA1 and BRCA2 mutations appear to account for a lower proportion of breast cancer patients at increased risk of harboring such mutations in Northern India (6/204, 2.9%) than has been reported in other populations. However, given the limited extent of reported family history among these patients, the observed mutation frequency is not dissimilar from that reported in other cohorts of early onset breast cancer patients. Several of the identified mutations are unique and novel to Indian patients

Intradermal administration of Rabies Vaccine at an affordable cost: Experience from tertiary care hospital in Jammu

Background: Rabies continue to be a major public health challenge in India. It can certainly be prevented by timely and appropriate administration of WHO recommended pre and post exposure prophylaxis. Intradermal regimen is running successfully and beneficial both in monetary as well as non-monetary terms. Aim& Objective:To evaluate the reduction in direct cost incurred with the use of intradermal regimen as compared to intramuscular regimen. Settings and Design: The present cross-sectional study was conducted in Government Medical College Jammu, a tertiary care centre. Methods and Material: A total of 17535 patients attending Anti Rabies Section of GMC Jammu were studied from Jan 2015 to September 2017.The patients belonging to Category II and III received 0.1 ml 2 site ID purified vero cell culture vaccine (PVCCV) on days 0, 3, 7 and 28 (2-2-2-0-2) and Rabies Immunoglobulin (RIG)(Category III only). Cost borne per patient receiving intradermal regimen was calculated and compared with cost borne in case Intramuscular regimen would have been used. Statistical analysis: Results were presented in descriptive manner using percentages and proportions. Conclusions: Intradermal regimen reduces the direct cost as compared to intramuscular regimen

Prevalence of hypothyroidism in pregnancy: An epidemiological study from 11 cities in 9 states of India

Background: A previous hospital based study from Delhi revealed a high prevalence of hypothyroidism in pregnant women. Several other studies with small sample size also indicate a rising trend of prevalence of hypothyroidism during pregnancy in India. Objective: To assess prevalence of hypothyroidism in pregnant women from various states/cities across India. Materials and Methods: This was a cross-sectional multicenter study conducted at Allahabad (Uttar Pradesh), Bengaluru (Karnataka), Chennai (Tamil Nadu), Kolkata (West Bengal), Hyderabad (Telangana), Nasik (Maharashtra), Rohtak (Haryana), Pune (Maharashtra), New Delhi (Delhi), Srinagar (Kashmir), and Vizag (Andhra Pradesh) enrolling 2599 pregnant women. Estimation of thyroid stimulating hormone (TSH), free T4, and antithyroid peroxidase (TPO) antibodies was carried out using Roche modular kit using ECLIA technology in a central laboratory. Results: We found in our study population that 13.13% of pregnant women have hypothyroidism (n = 388), using a cutoff TSH level of 4.5 μIU/ml. This prevalence was much higher using the American Thyroid Association criteria. Anti-TPO antibodies were positive in 20.74% of all pregnant women (n = 613), whereas 40% (n = 155) of hypothyroid pregnant women were positive for anti-TPO antibodies. Conclusion: This study concludes that there is a high prevalence of hypothyroidism (13.13%), majority being subclinical in pregnant women during the first trimester from India and universal screening of hypothyroidism may be desirable in our country