CYP1A1 gene polymorphisms: lack of association with breast cancer susceptibility in the southern region (Madurai) of India

The cytochrome P 450 1A1 gene encoding a phase I metabolic enzyme appears to be a candidate for breast cancer risk. It is involved in the phase I detoxification of polycyclic aromatic hydrocarbons (PAHs) and 2-hydroxylation of estrogens and mammary carcinogens into 2-hydroxy catechol metabolites. Several studies have investigated polymorphisms in CYP1A1 and breast cancer risk with inconsistent results. We here carried out a population based case-control study of the CYP MspI (CYP1A1*1/M1) and Ile462Val (CYP1A1*2/M2) polymorphisms in CYP1A1 to clarify their importance in determining breast cancer susceptibility in a South Indian population. A total of 50 cases and 50 controls were genotyped for both polymorphisms. We also investigated putative interactions with exposure to pollution, radiation and intake of tobacco and CYP1A1 genotype and breast cancer risk using a case only study design. The genotype distribution of CYP1A1*1 in cancer patients was 6% for homozygous (CYP1A1 M1 [C/C], 34% for heterozygous CYP1A1 M1 [T/C] and 60% for wild type (CYP1A1 M1 [T/T] (OR: 0.583, CI-95% (0.252-1.348). The genotype distribution of M2 genotypes in patients was 24% of homozygous (CYP1A1 M2 [Val/Val], 4% for heterozygous (CYP1A1 M2 [Ile/Val] and 72% for wild type allele (CYP1A1 M2 [Ile/Ile] [OR: 0.720, CI-95% (0.606-0.856)]. Our results suggest that there is no significant correlation between CYP1A1 M1/ CYP1A1 M2 polymorphism and occurrence of breast cancer in South Indian women.     

Estimation of Time Trends of Incidence of Prostate Cancer – an Indian Scenario

Background: With increase in life expectancy, adoption of newer lifestyles and screening using prostatespecific antigen (PSA), the incidence of prostate cancer is on rise. Globally prostate cancer is the second mostfrequently diagnosed cancer and sixth leading cause of cancer death in men. The present communication makesan attempt to analyze the time trends in incidence for different age groups of the Indian population reportedin different Indian registries using relative difference and regression approaches. Materials and Methods: Thedata published in Cancer Incidence in Five Continents for various Indian registries for different periods and/orpublications by the individual registries served as the source materials. Trends were estimated by computing themean annual percentage change (MAPC) in the incidence rates using the relative difference between two timeperiods (latest and oldest) and also by estimation of annual percentage change (EAPC) by the Poisson regressionmodel. Results: Age adjusted incidence rates (AAR) of prostate cancer for the period 2005-2008 ranged from 0.8(Manipur state excluding Imphal west) to 10.9 (Delhi) per 105 person-years. Age specific incidence rates (ASIR)increased in all PBCRs especially after 55 years showing a peak incidence at +65 years clearly indicating thatprostate cancer is a cancer of the elderly. MAPC in crude incidence rate(CR) ranged from 0.14 (Ahmedabad)to 8.6 (Chennai) . Chennai also recorded the highest MAPC of 5.66 in ASIR in the age group of 65+. Estimatedannual percentage change (EAPC) in the AAR ranged from 0.8 to 5.8 among the three registries. Increase intrend was seen in the 5-64 year age group cohort in many registries and in the 35-44 age group in Metropolitancities such as Delhi and Mumbai. Conclusions: Several Indian registries have revealed an increasing trend inthe incidence of prostate cancer and the mean annual percentage change has ranged from 0.14-8.6.     

Evaluation of total plasma homocysteine in Indian newborns using heel-prick samples

Objective To estimate total plasma homocysteine levels in Indian newborns by modifying the existing SBD-F based High performance liquid chromotography (HPLC) method in order to enable analysis in newborn heel-prick samples and assess the prevalence of hyperhomocysteinemia in Indian newborns who are exclusively breast-fed. Methods Reverse-phase HPLC with fluorescence detection for plasma homocysteine estimation and statistical analysis using student t-test. Results SBD-F based HPLC method was modified and Bland and Altman analysis was carried out to assess agreement between original and modified methods. The correlation co-efficient was 0.994. The limits of agreement (−5.9, 6.3) were small enough to apply new method in place of the old for heel-prick sample analysis. Total plasma homocysteine analysis was carried out on heel-prick samples of 607 randomly selected newborns (331 males and 276 females). The mean plasma homocysteine estimated by this method in Indian newborns was 6.99 (95% Cl: 6.48–7.49) with no appreciable gender effect (P=0.74). Elevated homocysteine levels were observed in 31 males and 21 females. Conclusions Modified HPLC method is validated and can be used for homocysteine analysis on newborn heel-prick samples. Using this method, the prevalence of hyperhomocysteinemia in Indian newborn is 8.6%     

Three-year prevalence and incidence of diabetes among American Indian youth in Montana and Wyoming, 1999 to 2001

OBJECTIVES: To estimate the prevalence and incidence of type 2 diabetes among American Indian youth. STUDY DESIGN: Medical records were reviewed annually for all patients with diabetes who were <20 years of age at 6 Indian Health Service facilities in Montana and Wyoming. All cases < or =5 years of age or weight per age < or =10th percentile at diagnosis or with islet cell antibodies were considered as probable type 1. Among the remaining cases, probable type 2 diabetes was defined when a child had one or more of the following characteristics: weight per age > or =95th percentile or acanthosis nigricans at diagnosis, elevated C-peptide or insulin, family history of type 2 diabetes; treatment with oral agents with or without insulin or no hypoglycemic therapy after 1 year of follow-up. RESULTS: From 1999 to 2001, 53% of prevalent cases and 70% of incident cases were categorized as probable type 2 diabetes. The average annual prevalence of probable type 1 and type 2 diabetes was 0.7 and 1.3 per 1000. The average annual incidence rates for probable type 1, and type 2 diabetes were 5.8, 23.3 per 100,000. CONCLUSIONS: The incidence of probable type 2 diabetes was approximately 4 times higher than type 1 diabetes among American Indian youth in Montana and Wyoming     

BRCA1 alterations are associated with endometriosis,but BRCA2 alterations show no detectable endometriosis risk: a study in Indian population

Purpose

To investigate the role of genetic variations and expression alterations of BRCA1 and BRCA2 genes in the pathophysiology of endometriosis.

Methods

A genetic association study was conducted in 573 endometriosis cases and 490 controls of Indian origin. We genotyped 13 selected promoter SNPs of BRCA1 gene and 2 selected promoter SNPs of BRCA2 gene by PCR-sequencing analysis. In addition, to better understand genetic contributions to the pathophysiology of endometriosis, the expression pattern of BRCA1 & 2 was analyzed in the eutopic endometria of endometriosis cases and controls by western-blot and immunohistochemical analysis.

Results

Our results revealed significant association between BRCA1 rs71361504 (−/GTT) SNP and endometriosis risk in Indian women (P < 0.0001), while the remaining SNPs of both BRCA1 & 2 genes showed no difference between cases and controls. Western-blot and immunohistochemical analysis revealed significantly decreased BRCA1 expression levels in eutopic endometria of patients compared with controls (P < 0.05). Furthermore, nuclear BRCA1 was frequently lost compared with cytoplasmic BRCA1 in eutopic endometria of patients. Expression of BRCA2 did not differ between patients and controls.

Conclusions

BRCA1 rs71361504 SNP may modify the endometriosis risk in Indian women. In addition, decreased expression of BRCA1 may play an important role in the pathophysiology of endometriosis. The analysis of BRCA1 genetic variants and/or expression might help to identify patients at high risk for disease outcome.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-014-0379-9) contains supplementary material, which is available to authorized users.     

Enzymatic studies and isoenzyme pattern of gammaglutamyl transpeptidase (GGTP) in Indian childhood cirrhosis (CC)

Histopathological studies of liver cell showing necrosis, parenchymal cell injury and microsomal cell damage are known to affect membrane bound enzymes such as gamma-glutamyl transpeptidase (GGTP), alkaline phosphatase (AP) and 5′-nucleotidase (5′-NT). The significant rise in GGTP, AP and 5′-NT indicates the damage of microsomes of parenchymal cell in Indian Childhood Cirrhosis (ICC) patients. SGPT/AP ratio may be an index for distinguishing ICC with other liver diseases. The isoenzyme pattern of GGTP in sera of control and ICC subjects have one band prominent activity. Similarly biopsy samples of control and ICC subjects show one prominent band of GGTP activity. The appearance of isoenzyme of GGTP in blood circulation is an index of microsome damage, cell necrosis and parenchymal cell injury. The isoenzyme pattern of GGTP could be a diagnostic test for ICC.     

Expression of alternate reading frame protein (F1) of hepatitis C virus in Escherichia coli and detection of antibodies for F1 in Indian patients

Apart from the core (21kD), a novel hepatitis C virus (HCV) frame shift protein (F1) is synthesized from the initiation codon of the polyprotein sequence followed by ribosomal frame shift into the -2/+1 reading frame. To date, no information is available on F1 protein of Indian isolates, and hence detection of antibodies for F1 protein in Indian patients assumes great relevance. Specific primers have been designed to amplify sequence coding for 120aa of truncated F1 (tF1). The amplified tF1 has been cloned in bacterial expression vector, pET21b for expression in Escherichia coli. Partially purified expressed protein has been subjected to western blot analysis using patients' sera. Three HCV positive sera employed in western analysis showed positive signals to tF1, while sera from uninfected individuals failed to give any signals. Further, results of western blots, carried out with patients sera titrated with purified core protein, confirmed the presence of antibodies specific to F1. The positive signal observed for F1 in western analysis with HCV infected sera suggests that F1 protein is synthesized in the natural course of HCV infection in Indian patients as well. Presence of antibodies against F1 protein of subtype 1c has been demonstrated, for the first time, in Indian patients.     

Infection Control in the Indian Health Service Dental Program: Estimated Costs and Effects on Productivity

The dental literature contains many recommendations defining standards for infection control. Little information is available, however, documenting the cost of implementing these standards. This article describes the cost incurred by the Indian Health Service Dental Program in the Oklahoma area between 1985 and 1988 for infection control. During this period, comprehensive infection control recommendations were published for oral health programs serving Native Americans and data were collected on supply utilization. While productivity data were collected for that same time period do not support the premise that infection control practices lead to decreased clinical productivity, infection control supply costs did increase over fourfold during this period.     

Indian hedgehog supports definitive erythropoiesis

Indian hedgehog (Ihh) has been reported to stimulate haematopoiesis ex vivo. In this study we studied the consequences of loss of function of Ihh for murine haematopoietic development. Ihh has no essential role in primitive erythropoiesis, but it is required in a non cell autonomous fashion for definitive erythropoieisis. Many components of the hedgehog signaling pathway are present in the fetal liver, with Ihh and Gli1 being most highly expressed in the stroma and Ptc1 being most highly expressed in haematopoietic stem and progenitor cells. Ihh knockout HSC and progenitor cell populations are produced in normal numbers in vivo and respond normally to haematopoietic cytokines in vitro, but terminal erythroid differentiation is defective leading to fatal anemia in mid gestation in many Ihh knockout embryos. These loss-of-function studies are consistent with previous gain-of-function studies which show Ihh can induce blood from ectoderm or expand HSCs in stroma-dependent culture.