Indian Cancer Resources Directory

Langerhan's Cell Histiocytosis

PTEN

Singh A, Mishra PK, Saluja SS, et al.
Prognostic Significance of HER-2 and p53 Expression in Gallbladder Carcinoma in North Indian Patients.
Oncology. 2016; 91(6):354-360 [PubMed] Related Publications

BACKGROUND/OBJECTIVE: Proto-oncogenes (HER-2) and tumor suppressor genes (p53) are commonly deregulated in gallbladder cancer (GBC). Available literature discloses skewed data from endemic Asian countries, especially north India. This study evaluates the prognostic significance of HER-2 and p53 in GBC patients from two major hospitals.
METHODS: Sixty resectable tumor and control specimens were prospectively collected from December 2012 to January 2016. Immunohistochemical staining was done using monoclonal antibodies to semiquantitatively evaluate HER-2 and p53 protein expression. The criterion for HER-2 positivity was set at >30% tumor cells showing complete, membranous staining while p53 positivity was established at <50% tumor cells showing complete nuclear staining. Clinicopathological correlations were drawn with major clinical outcomes.
RESULTS: It was observed that 36.67% (22/60) tumor cases and 5% (3/60) control cases showed strong HER-2 overexpression significantly correlating with sex, T-stage, nodal spread and distant metastasis (p < 0.05), while 33.3% (20/60) positivity was observed for p53 in tumor cases and 1.7% (1/60) in control cases. Multivariate analysis showed HER-2 (p = 0.04; hazard ratio: 2.36; 95% confidence interval: 1.04-5.33) and p53 (p = 0.03; hazard ratio: 5.63; 95% confidence interval: 1.21-26.26) expression to be independent prognostic factors.
CONCLUSION: Our study thus suggests the plausible role of HER-2 and p53 expression in worse prognosis of GBC in a north Indian population.

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Gallbladder Cancer

TP53

Mishra A, Singh V, Verma V, et al.
Current status and clinical association of beta-catenin with juvenile nasopharyngeal angiofibroma.
J Laryngol Otol. 2016; 130(10):907-913 [PubMed] Related Publications

OBJECTIVE: A possible role of the APC/beta-catenin pathway in the pathogenesis of sporadic juvenile nasopharyngeal angiofibroma has been suggested. This paper presents its current status and clinical association in our patients.
METHOD: A prospective observational study was conducted at King George Medical University and Central Drug Research Institute, in Lucknow, India. Western blot analysis was undertaken in 16 cases to examine beta-catenin expression. The clinical details were recorded along with follow up observations, to determine associations.
RESULTS: Up-regulation of beta-catenin expression was seen in 69 per cent of cases. The clinical variables did not reveal significant differences between patients with extremes of expression (extreme under- vs over-expression). However, absent expression was shown exclusively in young adults aged over 18 years, while enhanced expression was associated with an altered facial profile.
CONCLUSION: Although a beta-catenin association was seen in a subset of our sporadic juvenile nasopharyngeal angiofibroma cases, its expression was not homogeneous. This is in contrast to the Western literature that suggests a universal (homogenous) enhanced expression in the majority. Hence, further research is required to better define its molecular cascade.

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Nasopharyngeal Cancer

CTNNB1

Lohiya NK, Balasubramanian K, Ansari AS
Indian folklore medicine in managing men's health and wellness.
Andrologia. 2016; 48(8):894-907 [PubMed] Related Publications

India is a home for a large variety of plants with remarkable medicinal and pharmacological value. Traditional medicine in the form of Ayurveda, Siddha and Unani has used many of these plants since ancient days for treating and curing various ailments of the body. When it comes to issues related to reproductive health, people still hesitate to discuss and/or accept it openly and hence look for alternate and natural remedies. The various tribal populations distributed across different parts of the country still use these plant extracts in various formulations for maintenance of good health. The medical utilities of several of these plants have been documented; however, there are many more, whose potential is yet to be explored. This review discusses the role of various plants grown in the Indian subcontinent that have been widely used in maintaining various aspects of reproductive health in men such as infertility, aphrodisiac, contraception, libido, sexually transmitted infections and reproductive tract cancers as well as in treating chronic disorders.

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Prostate Cancer

Testicular Cancer

Hussain A, Tandon A, Prayaga AK, et al.
Cytomorphology and Histology Correlation of Rosai-Dorfman Disease: A 15-Year Study from a Tertiary Referral Centre in South India.
Acta Cytol. 2017; 61(1):55-61 [PubMed] Related Publications

OBJECTIVES: Rosai-Dorfman disease (RDD) is an uncommon, benign histiocytic disorder of unknown etiology, typically presenting in young adulthood. We highlight the cytomorphology of RDD and correlate it with the histopathology.
STUDY DESIGN: All cases diagnosed as RDD on fine-needle aspiration cytology between January 2001 and June 2015 were included. Clinical details were obtained from medical records. The cytology smears were reviewed along with the histopathology and immunohistochemistry, wherever available.
RESULTS: The study included 10 cases ranging in age from 11 to 68 years (median 29). There was a male predominance with a male:female ratio of 1.5:1. The patients commonly presented with bilateral cervical lymphadenopathy. Extranodal involvement was seen in 2 cases in the nose and mandible, respectively. Of these 10 cases, 8 were later biopsied. The cytological features included numerous crescentic histiocytes, emperipolesis, reactive lymphocytes and plasma cells. A histological diagnosis of RDD was made in 7 out of 8 cases, and 1 was diagnosed as Hodgkin lymphoma.
CONCLUSION: FNA represents an efficient, minimally invasive, cost-effective and reliable technique for the diagnosis of RDD and may obviate the need for further biopsy. However, the disease has close differential diagnoses, including Langerhans cell histiocytosis, granulomatous lesions, and Hodgkin lymphoma. Hence, it must be remembered that there can be pitfalls when the diagnosis is made by cytology alone.

Related:

Hodgkin's Lymphoma

Childhood Hodgkin's Lymphoma

Hodgkin Lymphoma - Molecular Biology

Gupta A, Ahmad MK, Mahndi AA, et al.
Promoter Methylation and Relative mRNA Expression of the p16 Gene in Cervical Cancer in North Indians.
Asian Pac J Cancer Prev. 2016; 17(8):4149-54 [PubMed] Related Publications

BACKGROUND: Cervical carcinoma is one of the main causes of mortality in women worldwide as well as in India. It occurs as a result of various molecular events that develop from the combined influences of an individual's genetic predisposition and external agents such as smoking and menstrual hygiene, for example. However, infection with human papillomavirus (HPV) is the established major risk factor. The aim of the current study was to investigate p16 CpG island methylation and establish any correlation with mRNA expression in a north Indian population.
MATERIALS AND METHODS: We analyzed 196 woman volunteers out of which 98 were cases and 98 healthy controls. For the analysis of methylation pattern, DNA extracted from blood samples was modified with a bisulfate kit and used as template for methylation specific PCR (MSP). Quantitative real-time PCR (QRT-PCR) was performed to check mRNA expression.
RESULTS: Correlation between methylation status of p16 gene and poor menstrual hygiene was significant (p=0.006), high parity cases showed methylation of p16 gene (p=0.031) with increased risk up to 1.86 times for cervical cancer and smoking was a strong risk factor associated with cervical cancer. We analyzed methylation pattern and found 60.3% methylation in cases with low mRNA expression level (0.014) as compared to controls (1.24). It was also observed that promoter methylation of p16 gene was significantly greater in FIGO stage III.
CONCLUSIONS: We conclude that p16 methylation plays an important role in cervical cancer in the north Indian population and its methylation decreases mRNA expression. It can be used as an important and consistent blood biomarker in cervical cancer patients.

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CDKN2A

Acute Lymphocytic Leukemia (ALL)

Anil S, Gopikrishnan PB, Basheer AB, et al.
Association of Poly (ADP-Ribose) Polymerase 1 Variants with Oral Squamous Cell Carcinoma Susceptibility in a South Indian Population.
Asian Pac J Cancer Prev. 2016; 17(8):4107-11 [PubMed] Related Publications

BACKGROUND: Oral cancers account for approximately 2% of all cancers diagnosed each year; however, the vast majority (80%) of the affected individuals are smokers whose risk of developing a lesion is five to nine times greater than that of non-smokers. Tobacco smoke contains numerous carcinogens that cause DNA damage, including oxidative lesions that are removed effectively by the base-excision repair (BER) pathway, in which poly (ADP-ribose) polymerase 1 (PARP-1), plays key roles. Genetic variations in the genes encoding DNA repair enzymes may alter their functions. Several studies reported mixed effects on the association between PARP-1 variants and the risk of cancer development. Till now no reported studies have investigated the association between PARP-1 variants and oral squamous cell carcinoma (OSCC) risk in an Indian population.
MATERIALS AND METHODS: In the present case control study 100 OSCC patients and 100 matched controls were genotyped using PARP1 single nucleotide peptides (SNP's) rs1136410 and rs3219090 using TaqMan assays.
RESULTS: The results indicated significantly higher risk with PARP1 rs1136410 minor allele "C" (OR=1.909; p=0.02942; CI, 1.060- 3.439). SNP rs1136410 also showed significantly increased risk in patients with smoking habit at C/C genotype and at minor allele C.
CONCLUSIONS: The PAPR-1 Ala762Val polymorphism may play a role in progression of OSCC. Larger studies with a greater number of samples are needed to verify these findings.

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Oral Cancer

PARP1

Bhandari P, Ahmad F, Mandava S, Das BR
Association of Genetic Variants in ARID5B, IKZF1 and CEBPE with Risk of Childhood de novo B-Lineage Acute Lymphoblastic Leukemia in India.
Asian Pac J Cancer Prev. 2016; 17(8):3989-95 [PubMed] Related Publications

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is a heterogeneous genetic disease and its etiology remains poorly understood. Recent genome wide association and replication studies have highlighted specic polymorphisms contributing to childhood ALL predispositions mostly in European populations. It is unclear if these observations generalize to other populations with a lower incidence of ALL. The current case-control study evaluated variants in ARID5B (rs7089424, rs10821936), IKZF1 (rs4132601) and CEBPE (rs2239633) genes, which appear most significantly associated with risk of developing childhood B-lineage ALL.
MATERIALS AND METHODS: Using TaqMan assays, genotyping was conducted for 162 de novo B-lineage ALL cases and 150 unrelated healthy controls in India. Appropriate statistical methods were applied.
RESULTS: Genotypic and allelic frequencies differed significantly between cases and controls at IKZF1-rs4132601 (p=0.039, p=0.015) and ARID5B-rs10821936 (p=0.028, p=0.026). Both rs10821936 (p=0.019; OR 0.67; 95% CI=0.47-0.94) and rs4132601 (p=0.018; OR 0.67; 95%CI 0.48-0.94) were associated with reduced disease risk. Moreover, gender- analysis revealed male-specific risk associations for rs10821936 (p=0.041 CT+CC) and rs4132601 (p=0.005 G allele). Further, ARID5B-rs7089424 and CEBPE-rs2239633 showed a trend towards decreased disease risk but without significance (p=0.073; p=0.73).
CONCLUSIONS: Our findings provide the rst evidence that SNPs ARID5B- rs10821936 and IKZF1-rs4132601 are associated with decreased B-lineage ALL susceptibility in Indian children. Understanding the effects of these variants in different ethnic groups is crucial as they may confer different risk of ALL within different populations.

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Childhood Acute lymphoblastic leukaemia (ALL)

ALL - Molecular Biology

ARID5B

Revathidevi S, Sudesh R, Vaishnavi V, et al.
Screening for the 3'UTR Polymorphism of the PXR Gene in South Indian Breast Cancer Patients and its Potential Role in Pharmacogenomics.
Asian Pac J Cancer Prev. 2016; 17(8):3971-7 [PubMed] Related Publications

BACKGROUND: Breast cancer, the commonest cancer among women in the world, ranks top in India with an incidence rate of 1,45,000 new cases and mortality rate of 70,000 women every year. Chemotherapy outcome for breast cancer is hampered due to poor response and irreversible dose-dependent cardiotoxicity which is determined by genetic variations in drug metabolizing enzymes and transporters. Pregnane X receptor (PXR), a member of the nuclear receptor superfamily, induces expression of drug metabolizing enzymes (DMEs) and transporters leading to regulation of xenobiotic metabolism.
MATERIALS AND METHODS: A genomic region spanning PXR 3' UTR was amplified and sequenced using genomic DNA isolated from 96 South Indian breast cancer patients. Genetic variants observed in our study subjects were queried in miRSNP to establish SNPs that alter miRNA binding sites in PXR 3' UTR. In addition, enrichment analysis was carried out to understand the network of miRNAs and PXR in drug metabolism using DIANA miRpath and miRwalk pathway prediction tools.
RESULTS: In this study, we identified SNPs rs3732359, rs3732360, rs1054190, rs1054191 and rs6438550 in the PXR 3; UTR region. The SNPs rs3732360, rs1054190 and rs1054191 were located in the binding site of miR-500a-3p, miR-532-3p and miR-374a-3p resulting in the altered PXR level due to the deregulation of post-transcriptional control and this leads to poor treatment response and toxicity.
CONCLUSIONS: Genetic variants identified in PXR 3' UTR and their effects on PXR levels through post-transcriptional regulation provide a genetic basis for inter- individual variability in treatment response and toxicity associated with chemotherapy.

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MicroRNAs

Shankar A, Roy S, Rath G, et al.
Change in Trend in Various Clinico-Pathological Factors and Treatment Profile of Breast Cancer Patients: a Tertiary Cancer Centre Experience.
Asian Pac J Cancer Prev. 2016; 17(8):3897-901 [PubMed] Related Publications

BACKGROUND: Breast cancer is by far the most frequent cancer of women (23% of all cancers), ranking second overall when both sexes are considered together. Since there has been change in clinico-pathological factors and treatment profiles for breast cancer patients over the years, the present study to evaluate the change trends in India.
MATERIALS AND METHODS: A detailed analysis was carried out with respect to age, menopausal status, family history, disease stage, surgery performed, histopathology, hormone receptor status, and use of chemotherapy or hormonal therapy. Change in various clinico-pathological factors and treatments of breast cancer cases was recorded and analysed.
RESULTS: Mean age at presentation was found to be earlier in 2005-2006 compared with 1997-98 (p value: 0.046). More premenopausal women were diagnosed with breast cancer in 2005-2006 when this was compared with initial years of assessment (p value ≤0.001). When change in the receptor status was evaluated, we observed that there was a decrease in cases of ER and PR receptor positivity which was significant (p value: 0.007). Over the period of time, more f patients were not offered surgery initially in view of advanced disease when the two time periods were compared (p value: ≤0.001). There was a significant increase in patients who were initially offered neo-adjuvant chemotherapy in view of advanced disease at presentation (p value: ≤0.001). There was increasing number of patients who received palliative treatment for symptoms in 2005-2006 when compared to patients treated in 1997-98((p value: ≤0.001).
CONCLUSIONS: Changes in mean age at presentation, premenopausal status, and stage at presentation have occurred over the years. More aggressive patterns of disease have become more common with early age at presentation and aggressive biological behaviour with receptor negative tumours.

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Cancer Prevention and Risk Reduction

Chatterjee S, Chattopadhyay A, Senapati SN, et al.
Cancer Registration in India - Current Scenario and Future Perspectives.
Asian Pac J Cancer Prev. 2016; 17(8):3687-96 [PubMed] Related Publications

Cancer registration, an important component of cancer surveillance, is essential to a uni ed, scienti c and public health approach to cancer prevention and control. India has one of the highest cancer incidence and mortality rates in the world. A good surveillance system in the form of cancer registries is important for planning and evaluating cancer-control activities. Cancer registration in India was initiated in 1964 and expanded since 1982, through initiation of the National Cancer Registry Program (NCRP) by the Indian Council of Medical Research. NCRP currently has twenty-six population based registries and seven hospital based registries. Yet, Indian cancer registries, mostly in urban areas, cover less than 15% of the population. Other potential concerns about some Indian registries include accuracy and detail of information on cancer diagnosis, and timeliness in updating the registry databases. It is also important that necessary data collection related quality assurance measures be undertaken rigorously by the registries to ensure reliable and valid information availability. This paper reviews the current status of cancer registration in India and discusses some of the important pitfalls and issues related to cancer registration. Cancer registration in India should be complemented with a nationwide effort to foster systematic investigations of cancer patterns and trends by states, regions and sub populations and allow a continuous cycle of measurement, communication and action.

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Chatterjee S, Chattopadhyay A, Samanta L, Panigrahi P
HPV and Cervical Cancer Epidemiology - Current Status of HPV Vaccination in India.
Asian Pac J Cancer Prev. 2016; 17(8):3663-73 [PubMed] Related Publications

Cervical cancer (CaCx) is the second most fatal cancer contributing to 14% of cancers in Indian females, which account for 25.4% and 26.5% of the global burden of CaCx prevalence and mortality, respectively. Persistent infection with high-risk human papilloma virus (HPV- strains 16 and 18) is the most important risk factor for precursors of invasive CaCx. Comprehensive prevention strategies for CaCx should include screening and HPV vaccination. Three screening modalities for CaCx are cytology, visual inspection with acetic acid, and HPV testing. There is no Indian national policy on CaCx prevention, and screening of asymptomatic females against CaCx is practically non-existent. HPV vaccines can make a major breakthrough in the control of CaCx in India which has high disease load and no organized screening program. Despite the Indian Government's effort to introduce HPV vaccination in the National Immunization Program and bring down vaccine cost, challenges to implementing vaccination in India are strong such as: inadequate epidemiological evidence for disease prioritization, duration of vaccine use, parental attitudes, and vaccine acceptance. This paper reviews the current epidemiology of CaCx and HPV in India, and the current status of HPV vaccination in the country. This article stresses the need for more research in the Indian context, to evaluate interventions for CaCx and assess their applicability, success, scalability and sustainability within the constraints of the Indian health care system.

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Human Papillomavirus (HPV), Vaccination, and Cervical Cancer

Bahl C, Singh N, Behera D, Sharma S
Association of polymorphisms in Dickopff (DKK) gene towards modulating risk for lung cancer in north Indians.
Future Oncol. 2017; 13(3):213-232 [PubMed] Related Publications

AIM: To investigate the association between the genetic variants of DKK4 (rs2073664), DKK3 (rs2291599, rs3206824 and rs7391689) and DKK2 (rs447372, rs419558 and rs17037102) and lung cancer predisposition in north Indians.
MATERIALS & METHODS: A total of 600 subjects were genotyped using PCR restriction fragment length polymorphism technique. Association analysis was carried out using logistic regression approach.
RESULTS: DKK3 rs7396187 showed a protective effect (p = 0.01). Subjects with heterozygous genotype of DKK2 rs17037102 and rs419558 showed an increased risk. The variant genotype of the genotypic combination, DKK3 rs3206824 and DKK2 rs419558 showed a twofold increased risk (p = 0.008). Lung cancer risk increased four-times in subjects with variant genotype of all the three DKK2 variants.
CONCLUSION: DKK2 is certainly playing a crucial role in modulating cancer susceptibility.

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Cancer Prevention and Risk Reduction

Godbole SV, Nandy K, Gauniyal M, et al.
HIV and cancer registry linkage identifies a substantial burden of cancers in persons with HIV in India.
Medicine (Baltimore). 2016; 95(37):e4850 [PubMed] Related Publications

We utilized computerized record-linkage methods to link HIV and cancer databases with limited unique identifiers in Pune, India, to determine feasibility of linkage and obtain preliminary estimates of cancer risk in persons living with HIV (PLHIV) as compared with the general population.Records of 32,575 PLHIV were linked to 31,754 Pune Cancer Registry records (1996-2008) using a probabilistic-matching algorithm. Cancer risk was estimated by calculating standardized incidence ratios (SIRs) in the early (4-27 months after HIV registration), late (28-60 months), and overall (4-60 months) incidence periods. Cancers diagnosed prior to or within 3 months of HIV registration were considered prevalent.Of 613 linked cancers to PLHIV, 188 were prevalent, 106 early incident, and 319 late incident. Incident cancers comprised 11.5% AIDS-defining cancers (ADCs), including cervical cancer and non-Hodgkin lymphoma (NHL), but not Kaposi sarcoma (KS), and 88.5% non-AIDS-defining cancers (NADCs). Risk for any incident cancer diagnosis in early, late, and combined periods was significantly elevated among PLHIV (SIRs: 5.6 [95% CI 4.6-6.8], 17.7 [95% CI 15.8-19.8], and 11.5 [95% CI 10-12.6], respectively). Cervical cancer risk was elevated in both incidence periods (SIRs: 9.6 [95% CI 4.8-17.2] and 22.6 [95% CI 14.3-33.9], respectively), while NHL risk was elevated only in the late incidence period (SIR: 18.0 [95% CI 9.8-30.20]). Risks for NADCs were dramatically elevated (SIR > 100) for eye-orbit, substantially (SIR > 20) for all-mouth, esophagus, breast, unspecified-leukemia, colon-rectum-anus, and other/unspecified cancers; moderately elevated (SIR > 10) for salivary gland, penis, nasopharynx, and brain-nervous system, and mildly elevated (SIR > 5) for stomach. Risks for 6 NADCs (small intestine, testis, lymphocytic leukemia, prostate, ovary, and melanoma) were not elevated and 5 cancers, including multiple myeloma not seen.Our study demonstrates the feasibility of using probabilistic record-linkage to study cancer/other comorbidities among PLHIV in India and provides preliminary population-based estimates of cancer risks in PLHIV in India. Our results, suggesting a potentially substantial burden and slightly different spectrum of cancers among PLHIV in India, support efforts to conduct multicenter linkage studies to obtain precise estimates and to monitor cancer risk in PLHIV in India.

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Kumari A, Bahl C, Singh N, et al.
Association of p53 codon 72 polymorphism and survival of North Indian lung cancer patients treated with platinum-based chemotherapy.
Mol Biol Rep. 2016; 43(12):1383-1394 [PubMed] Related Publications

p53 helps in maintaining genomic stability by undergoing cellular arrest, DNA repair or cellular apoptosis during DNA damage. So, as to find the association of p53Arg (72) Pro towards lung carcinogenesis and overall survival of North Indian lung cancer patients, single nucleotide polymorphic variant (rs1042522) was analyzed. 840 subjects including 420 cases and 420 controls were recruited and genotyped using PCR-RFLP technique for p53Arg (72) Pro polymorphic site. Association was analyzed using adjusted odds ratio along with its confidence intervals (95 % CI) and p value predicted from logistic regression whereas overall survival for lung cancer patients was obtained using Kaplan-Meir and Cox regression model for different parameters to obtain hazard ratio and survival time with statistical significance (log-rank p value). None of the variant genotypes for p53Arg (72) Pro showed any association towards lung cancer risk or any specific histological subtype. Lung cancer subjects with Pro/Pro genotype had better median survival time as compared to Arg/Pro genotype (10 months; HR = 0.65; 95 % CI = 0.45-0.95; p = 0.03). Furthermore, female lung cancer patients with Arg/Pro (HR = 0.08; 95 % CI = 0.02-0.34; p = 0.0005) and Pro/Pro (HR = 0.21; 95 % CI = 0.06-0.67; p = 0.008) genotypes showed a better overall survival and hence a better prognosis as compared to males. Our data also reveals that lung cancer patients with ECOG scores between 0 and 1 and carrying the Pro/Pro had better chances of survival. p53 codon 72 polymorphism could play a role as a prognostic marker in lung cancer patients.

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TP53

Singh MP, Kaur M, Gupta N, et al.
Prevalence of high-risk human papilloma virus types and cervical smear abnormalities in female sex workers in Chandigarh, India.
Indian J Med Microbiol. 2016 Jul-Sep; 34(3):328-34 [PubMed] Related Publications

PURPOSE: Cervical cancer is the most common cancer among women in developing nations. Nearly 90% of the cases have been linked to the presence of high-risk human papillomavirus (hrHPV) types 16 and 18. The risk of cervical cancer may be high in female sex workers (FSWs) due to multiple sexual partners. This study aimed to determine the prevalence of cytological abnormalities and hrHPV types 16 and 18 in FSWs in Chandigarh, North India using the liquid-based cytology (LBC) approach.
MATERIALS AND METHODS: The cervical brush samples were collected from 120 FSW and 98 age-matched healthy controls (HCs). These were subjected to pap smear using conventional method, LBC and the detection of hrHPV types 16 and 18 was carried out using polymerase chain reaction.
RESULTS: The LBC samples showed better cytological details and also reduced the number of unsatisfactory smears from 11% in Pap to 1.5% in the LBC. A significantly higher number of inflammatory smears were reported in FSWs (51.7% vs. 34.7%, P = 0.01). The hrHPV types 16/18 were detected in 33/120 (27.5%) FSW versus 23/98 (23.5%) HCs. The risk of acquiring hrHPV was higher in FSWs, who had age at first sex ≤25 years, higher income and the habit of smoking.
CONCLUSION: The high prevalence of hrHPV among FSWs and HCs suggests the need for the implementation of effective National Screening Programme for early detection of hrHPV types to decrease the burden of cervical cancer, especially in high-risk population.

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Govindarajan GV, Bhanumurthy L, Balasubramanian A, Ramanathan A
A Novel Mutation in the DNA Binding Domain of NFKB is Associated with Speckled Leukoplakia.
Asian Pac J Cancer Prev. 2016; 17(7):3627-9 [PubMed] Related Publications

BACKGROUND: Activation and inactivation of nuclear factor of kappa light chain gene enhancer in B cells (NFKB) is tightly regulated to ensure effective onset and cessation of defensive inflammatory signaling. However, mutations within NFKB, or change in activation and inactivation molecules have been reported in a few cancers. Although oral squamous cell carcinoma is one of the most prevalent forms of cancer in India, with a development associated with malignant transformation of precancerous lesions, the genetic status of NFKB and relative rates of change in oral precancerous lesions remain unknown. Hence in the present study we investigated all twenty four exons of NFKB gene in two precancerous lesions, namely oral submucous fibrosis (OSMF) and oral leukoplakia (OL) to understand its occurrence, incidence and assess its possible contribution to malignant transformation.
MATERIALS AND METHODS: Chromosomal DNA isolated from twenty five each of OSMF and OL tissue biopsy samples were subjected to PCR amplification with intronic primers flanking twenty four exons of the NFKB gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status.
RESULTS: Sequence analysis identified a novel heterozygous mutation, c.419T>A causing substitution of leucine with glutamine at codon 140 (L140Q) in an OL sample.
CONCLUSIONS: The identification of a substitution mutation L140Q within the DNA binding domain of NFKB in OL suggests that NFKB mutation may be relatively an early event during transformation. To the best of our knowledge, this study is the first to have identified a missense mutation in NFKB in OL.

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Oral Cancer

Ikoma T, Kapoor VK, Behari A, et al.
Lack of an Apparent Association between Mycotoxin Concentrations in Red Chili Peppers and Incidence of Gallbladder Cancer in India : an Ecological Study.
Asian Pac J Cancer Prev. 2016; 17(7):3499-503 [PubMed] Related Publications

Our recent studies conducted in South America have shown that mycotoxin contamination of red chili peppers (RCPs) may be associated with an increased risk of gallbladder cancer (GBC). Whether this relationship exists in India, a country with a high incidence of GBC and high consumption of RCPs, is unclear. We therefore measured concentrations of aflatoxins (AFs) and ochratoxin A (OTA) in RCPs from areas of low, medium, and high incidence of GBC in India, and compared these concentrations with GBC incidence in each area. Twentyone RCP samples were collected from nine cities (eight from a lowincidence area, five from a mediumincidence area, and eight from a highincidence area). Concentrations of AFs and OTA were measured using highperformance liquid chromatography. No significant differences in mean concentrations of AFs and OTA were found in the three areas. AFB1 levels in the lowincidence area (10.81 ?g/kg) and highincidence area (12.00 ?g/kg) were more than 2.2 and 2.4 times higher compared with the maximum permitted level of AFB1 in spices (5.0 ?g/kg) set by the Commission of the European Communities, or that (4.4 ?g/kg) obtained in our previous study in Chile. Our results show that the mean concentrations of mycotoxins in RCPs are similar among the three areas in India with different incidences of GBC. Further studies with human subjects are needed to evaluate any association between AFB1 and GBC.

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Gallbladder Cancer

Singh R, Bhatt ML, Singh SP, et al.
Expression Levels of Tetraspanin KAI1/CD82 in Breast Cancers in North Indian Females.
Asian Pac J Cancer Prev. 2016; 17(7):3431-6 [PubMed] Related Publications

BACKGROUND: Carcinogenesis is a multifaceted intricate cellular mechanism of transformation of the normal functions of a cell into neoplastic alterations. Metastasis may result in failure of conventional treatment and death Hence, research on metastatic suppressors in cancer is a high priority. The metastatic suppressor gene CD82, also known as KAI1, is a member of the transmembrane 4 superfamily which was first identified in carcinoma of prostate. Little work has been done on this gene in breast cancer. Herein, we aimed to determine the gene and protein level expression of CD82/KAI1 in breast cancer and its role as a prognosticator.
MATERIALS AND METHODS: In this study, 83 histologically proven cases of breast cancer and a similar number of controls were included. Patient age ranged from 1870 years. Quantitative Real Time Polymerase Chain Reaction (qRT PCR) and immunohistochemistry (IHC) were used to investigate KAI1 expression at gene and protein levels, respectively. Statistical analysis was done to correlate expression of KAI1 and clinicopathological parameters.
RESULTS: It was revealed that: (i) KAI1 was remarkably diminished in metastatic vs non metastatic breast cancer both at the gene and the protein levels (P<.05); (ii) KAI1 expression levels were strongly correlated with TNM staging, histological grade and advanced stage (p<0.001) and no association was found with any other studied parameter; (iii) Lastly, a significant correlation was observed between expression of KAI1 and overall median survival of BC patients (P = 0.04).
CONCLUSIONS: Our results suggest that lack of expression of the KAI1 might indicate a more aggressive form of breast cancer. Loss of KAI1 may be considered a significant prognostic marker in predicting metastatic manifestation. When evaluated along with the clinical and pathological factors, KAI1 expression may be beneficial to tailor aggressive therapeutic strategies for such patients.

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CD82

Borthakur P, Kataki K, Keppen C, et al.
Expression of Epstein Barr Virus Encoded EBNA1 and LMP1 Oncoproteins in Nasopharyngeal Carcinomas from Northeast India.
Asian Pac J Cancer Prev. 2016; 17(7):3411-6 [PubMed] Related Publications

BACKGROUND: Nasopharyngeal carcinoma (NPC), a malignancy arising from the epithelial lining of the nasopharynx, is distinct from others cancers in terms of its epidemiologic features. It is rare in most parts of the world except for a few regions with populations of Mongoloid origin.
OBJECTIVES: To study the expression pattern of Epstein Barr virus (EBV) encoded oncoproteins EBNA1 and LMP1 in different histological types of NPC and to correlate expression patterns with sex, age and histological types.
MATERIALS AND METHODS: A total of 40 formalinfixed, paraffinembedded NPC biopsy samples and tissues from 20 healthy controls were collected to study the expression level of EBNA1 and LMP1 using immunohistochemistry.
RESULTS: EBNA1 and LMP1 expression was found in 92.5% and 90% respectively, of the cases and none of the control specimens. The expression patterns of EBNA1 and LMP1 were determined to be statistically significant (p<0.05) when correlated with sex, age and histological distributions. Also immunohistochemistry was found to be a sensitive technique in the detection of EBV.
CONCLUSIONS: The study reveals that the potent oncoproteins EBNA1 and LMP1 were over expressed in our population cohort. Our findings are to some extent inconsistent with earlier reports as our population showed a higher expression of both EBNA1 and LMP1 compared to other studies.

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Nasopharyngeal Cancer

Dahiya N, Acharya AS, Bachani D, et al.
Quality of Life of Patients with Advanced Cervical Cancer before and after Chemoradiotherapy.
Asian Pac J Cancer Prev. 2016; 17(7):3095-9 [PubMed] Related Publications

BACKGROUND: Cervical cancer is the most frequently diagnosed cancer among women in India. Understanding quality of life (QOL) in women undergoing chemoradiotherapy for cervical cancer will help in introducing interventions for better care and outcomes in these women. This study assessed QOL before and after chemo radiotherapy in cervical cancer patients.
MATERIALS AND METHODS: This followup study covered sixtyseven newly diagnosed women with advanced cervical cancer (stages 2b to 4b). Structured questionnaires (the European Organization for Research and Treatment of Cancer, EORTC QLQC30 and EORTC QLQCX24) were used to assess the change in QOL after 6 months of treatment.
RESULTS: The mean age of women at the time of detection of cervical cancer was 52.3±11.29 years (Range 3075 years). Six months survival was 92.53%. The mean global health score of cervical cancer patients after six months of treatment was 59.52, which was significantly higher than the pretreatment score of 50.15 (p=0.00007). Physical, cognitive and emotional functioning improved significantly (p<0.05) after treatment. Fatigue, pain, insomnia and appetite loss improved but episodes of diarrhea increased after treatment. The mean "symptoms score" using EORTC QLQCX24 post treatment was 20.0 which was significantly lower as compared to the pre treatment score 30.0 (p<0.00001). Sexual enjoyment and sexual functioning decreased significantly after treatment.
CONCLUSIONS: QOL of newly diagnosed cervical cancer patients improved significantly following chemoradio therapy. Enhancement was also demonstrated on three of the five functional scales of EORTC QLQC30. To further improve QOL, interventions focusing on social and psychological support and physical rehabilitation may be needed.

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Iqbal B, Masood A, Lone MM, et al.
Polymorphism of Metastasis Suppressor Genes MKK4 and NME1 in Kashmiri Patients with Breast Cancer.
Breast J. 2016; 22(6):673-677 [PubMed] Related Publications

Genetic polymorphisms in metastatic suppressor genes like MKK4 and NME1 are not well studied in breast cancer. Hence, we analyzed the relationship between MKK4 and NME1 polymorphisms and breast cancer risk in Kashmir, India. The different genotypes of NME1 and MKK4 genes were analyzed by polymerase chain reaction and restriction fragment length polymorphism in 130 breast cancer cases and 200 age- and sex-matched controls. Conditional logistic regression models were used to assess the association of various genotypes with breast cancer. In this study, we found an inverse association between MKK4 promoter polymorphism and breast cancer risk. As compared to TT (wild) genotype, individuals with TG (heterozygous) (OR = 0.32; 95% CI = (0.17-0.58) and GG (mutant) (OR = 0.13; CI = 0.04-0.40) genotypes showed decreased risk of breast cancer. When participants were classified on the basis of lymph node involvement, a strong association between NME1 heterozygous genotype (OR = 3.82; CI = (1.54-9.44) and breast cancer was found.

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MAP2K4

NME1

Bal A, Singh N, Agarwal P, et al.
ALK gene rearranged lung adenocarcinomas: molecular genetics and morphology in cohort of patients from North India.
APMIS. 2016; 124(10):832-8 [PubMed] Related Publications

ALK gene rearrangement in the lung adenocarcinomas is the second most common (1.6-11.7% of NSCLC) targetable genomic change after EGFR mutations. However, the prevalence and clinicopathological features of ALK-rearranged lung adenocarcinomas from North India are lacking. A total of 240 cases of lung adenocarcinoma were screened for EGFR mutations and for ALK expression. Smoking status, TNM stage, and treatment response were recorded in all cases. Out of 240 cases screened, 37 cases were positive for EGFR mutations and 17 cases (7.08%) showed ALK positivity with immunohistochemistry and break-apart FISH. On excluding 37 EGFR mutation-positive cases, the incidence of ALK-positive adenocarcinoma appears to be higher (17/203 cases, 8.03%). Eight were men and nine were women with mean age of 51.7 years. Majority (62.5%) were non-smokers and had unresectable disease (70.6% stage IV, 17.6% IIIB). The morphological patterns noted were solid (12 cases), papillary (four cases), and micropapillary (one case). Signet ring (two cases) and clear cell change (one cases) were noted. Out of five patients who received crizotinib, three had partial response and two had stable disease. ALK-rearranged lung adenocarcinomas account for a minor proportion of NSCLC with prevalence similar to that reported in literature. However, as contrast to published data in our series, patients were in older age group and had solid and papillary pattern on morphology with an aggressive course.

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FISH

Cancer Screening and Early Detection

EGFR

ALK

Mishra GA, Pimple SA, Shastri SS
Prevention of Cervix Cancer in India.
Oncology. 2016; 91 Suppl 1:1-7 [PubMed] Related Publications

Cervical cancer is the fourth most common cancer among women globally and the second most common cancer among Indian women. India alone bears 23% of the global cervical cancer burden. In India, population-based cervical cancer screening is largely nonexistent in most regions due to competing healthcare priorities, insufficient financial resources and a limited number of trained providers. Hence, most of the cases present in advanced stages of the disease, thus leading to increased mortality and reduced survival. Various screening options like cytology, visual-based screening and testing for high-risk HPV are available. Several cross-sectional studies have looked at the comparative efficacy of different screening tests. Three important randomized controlled trials from India have shown the efficacy of screening once in a life time with HPV DNA, one-time screening with VIA by trained nurses and four-time screening with VIA by trained primary health workers, reducing mortality due to cervical cancers. Prevention of cervical cancers with two-dose HPV vaccination and early detection of precancerous cervical lesions of the eligible population through screening and their appropriate treatment with a single-visit 'screen-and-treat' approach appear to be promising for low-middle-income countries including India.

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Human Papillomavirus (HPV), Vaccination, and Cervical Cancer

Malik PS, Jain D, Kumar L
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Advanced Non-Small Cell Lung Cancer.
Oncology. 2016; 91 Suppl 1:26-34 [PubMed] Related Publications

The advent of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has led to a paradigm shift in the management of advanced adenocarcinoma of the lung. The key to success of these therapies lies in the precise identification of their molecular targets, i.e. sensitizing EGFR mutations. The variations in the prevalence of these mutations among different ethnicities necessitate regional studies for a better understanding of the molecular epidemiology of the disease and clinical decision-making. This is even more relevant for countries like India where genetic heterogeneity is a rule. Here, we make an attempt to review the epidemiology of EGFR mutations in India versus other Asian countries and the West. We also review the clinical experience with EGFR TKIs and suggest the way forward in a resource-limited setting.

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Non-Small Cell Lung Cancer

Nair R, Arora N, Mallath MK
Epidemiology of Non-Hodgkin's Lymphoma in India.
Oncology. 2016; 91 Suppl 1:18-25 [PubMed] Related Publications

Non-Hodgkin's lymphoma (NHL) is a common hematological malignancy. The age-adjusted incidence rates for NHL in men and women in India are 2.9/100,000 and 1.5/100,000, respectively. These are about one fourth of the incidence rates reported from Western Europe or North America. Within India, the incidence is several-fold higher in urban cancer registries compared to rural areas; the incidence being higher in metropolitan cities and Indian immigrants suggesting that urban lifestyles and economic progress may increase the cancer incidence. Compared to developed nations, the key differences in the presentation in India include: median age of 54 years (almost a decade less), higher male to female ratio, higher proportion of patients with B-symptoms (40-60 vs. 20-30%), poor ECOG performance status (≥2) at diagnosis (50 vs. 20-30%), higher frequency of diffuse large B-cell lymphomas (60-70 vs. <40%), lower frequency of follicular NHL (<20 vs. 30-40%) and T-cell type in 10-20 vs. <10%. The estimated mortality rate due to NHL is higher in India than in North America and Western Europe. Diagnostic and treatment delays, incorrect diagnosis and inappropriate or suboptimal treatment may be possible reasons for the poor outcome. Any improvement in the outcomes for NHL in India will require a nationwide approach, e.g. creation of several regional and district-level centers with expertise in lymphoma management. Collection of data on patient- and disease-related characteristics, treatment outcome, development of infrastructure, centralized review of histopathology subtype, novel treatment protocols, rigorous follow-up, training of staff, and financial support towards treatment could be possible strategies to improve the outcome.

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Non Hodgkin's Lymphoma

Kadla SA, Shah NA, Bindroo MA, et al.
Evaluation of iron deficiency anaemia for gastrointestinal causes in patients without GI symptoms in high prevalent GI malignancy zones.
Arab J Gastroenterol. 2016; 17(2):67-72 [PubMed] Related Publications

BACKGROUND AND STUDY AIMS: Gastric cancer is highly prevalent in Kashmir, as are lower gastrointestinal (LGI) malignancies. Colonic cancer, gastric cancer, and coeliac disease are the most important gastrointestinal (GI) causes of iron deficiency anaemia (IDA) worldwide. Approximately 9% of patients with IDA present with a suspicious lesion in the GI tract upon examination. However, the absence of GI symptoms and a possible lesion accounting for blood loss in IDA have not been studied in this zone with a high prevalence of GI malignancy. We aimed to examine IDA patients without GI symptoms to determine the most plausible cause of their blood loss.
PATIENTS AND METHODS: A total of 100 patients with IDA and 250 control subjects without IDA and referred for gastrointestinal endoscopy were enrolled in a cross-sectional, comparative study. Patients presenting with a significant lesion proportionate to their anaemia in the upper GI tract were not examined further, if no further strong indications were present.
RESULTS: Twenty-nine patients (29%) were found to have malignancy: 13 with gastric cancer and 16 with colonic malignancies. Other apparent causes of GI blood loss included peptic ulcer disease in 10 (10%) patients, haemorrhoids in 22 (25%), polyps in eight (three in the upper GI tract and five in the LGI tract), gastric erosions in eight (8%), and angiodysplasia, diverticulitis, and trichuriasis in two (2%) each.
CONCLUSION: In light of the high incidence of GI malignancies in this patient group, a low threshold for GI screening as well as mass screening for IDA is needed.

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Stomach Cancer

Gastric Cancer

Mathew A, George PS, Arjunan A, et al.
Temporal Trends and Future Prediction of Breast Cancer Incidence Across Age Groups in Trivandrum, South India.
Asian Pac J Cancer Prev. 2016; 17(6):2895-9 [PubMed] Related Publications

BACKGROUND: Increasing breast cancer (BC) incidence rates have been reported from India; causal factors for this increased incidence are not understood and diagnosis is mostly in advanced stages. Trivandrum exhibits the highest BC incidence rates in India. This study aimed to estimate trends in incidence by age from 2005- 2014, to predict rates through 2020 and to assess the stage at diagnosis of BC in Trivandrum.
MATERIALS AND METHODS: BC cases were obtained from the Population Based Cancer Registry, Trivandrum. Distribution of stage at diagnosis and incidence rates of BC [Age-specific (ASpR), crude (CR) and age-standardized (ASR)] are described and employed with a joinpoint regression model to estimate average annual percent changes (AAPC) and a Bayesian model to estimate predictive rates.
RESULTS: BC accounts for 31% (2681/8737) of all female cancers in Trivandrum. Thirty-five percent (944/2681) are <50 years of age and only 9% present with stage I disease. Average age increased from 53 to 56.4 years (p=0.0001), CR (per 105 women) increased from 39 (ASR: 35.2) to 55.4 (ASR: 43.4), AAPC for CR was 5.0 (p=0.001) and ASR was 3.1 (p=0.001). Rates increased from 50 years. Predicted ASpR is 174 in 50-59 years, 231 in > 60 years and overall CR is 80 (ASR: 57) for 2019- 20.
CONCLUSIONS: BC, mostly diagnosed in advanced stages, is rising rapidly in South India with large increases likely in the future; particularly among post-menopausal women. This increase might be due to aging and/or changes in lifestyle factors. Reasons for the increased incidence and late stage diagnosis need to be studied.

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