RESUMO
The association of nucleotide excision repair (NER) gene polymorphisms with esophageal squamous cell carcinoma (ESCC) is inconclusive. The aim of the current study was to assess the association of repair gene xeroderma pigmentosum A (XPA) (rs-1800975) and xeroderma pigmentosum C (XPC) (rs-2228000) polymorphisms with ESCC risk as well as modifying effects of environmental factors. The genotyping was done in 450 confirmed ESCC cases and equal number of individually matched controls by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and direct sequencing methods. Conditional logistic regression models were used to assess the genotypic associations and interactions. A high ESCC risk was found in subjects who carried the homozygous minor allele of XPA (odds ratio (OR) = 3.57; 95 % confidence interval (CI) = 1.76-7.23), and the risk was higher when analysis was limited to participants who were ever smokers (OR = 4.22; 95 % CI = 2.01-8.88), lived in adobe houses (OR = 8.42; 95 % CI = 3.74-18.95), consumed large volumes of salt tea (OR = 7.42; 95 % CI = 3.30-16.69), or had a positive family history of cancer (FHC) (OR = 9.47; 95 % CI = 4.67-19.20). In case of XPC, a homozygous minor allele also showed strong association with ESCC risk (OR = 4.43; 95 % CI = 2.41-8.16). We again observed a very strong effect of the above environmental factors in elevating the risk of ESCC. Further, the variant genotypes of both genes in combination showed an increased risk towards ESCC (OR = 7.01; 95 % CI = 3.14-15.64) and such association was synergistically significant. Salt tea consumption showed an interaction with genotypes of XPA and XPC. However, an interaction with FHC was significant in the case of XPA genotype only. XPA and XPC genotypes are associated with an increased risk of ESCC, and such association was reasonably modulated by different exposures.
Assuntos
Carcinoma de Células Escamosas/genética , Proteínas de Ligação a DNA/genética , Neoplasias Esofágicas/genética , Polimorfismo de Nucleotídeo Único , Proteína de Xeroderma Pigmentoso Grupo A/genética , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Sequência de Bases , Bebidas , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Materiais de Construção , Reparo do DNA , Proteínas de Ligação a DNA/fisiologia , Dieta , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etiologia , Feminino , Frequência do Gene , Interação Gene-Ambiente , Genótipo , Habitação , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Risco , Fumar/epidemiologia , Fatores Socioeconômicos , Proteína de Xeroderma Pigmentoso Grupo A/fisiologiaRESUMO
Studies have associated secondhand smoking (SHS) with cancers of the lung, larynx, and pharynx. Only a few studies have examined the association between SHS and esophageal squamous cell carcinoma (ESCC) and the findings are inconclusive. We aimed to investigate the association between SHS and risk of ESCC in a case-control study in Kashmir, where the incidence of ESCC is high. We recruited 703 histopathologically confirmed ESCC cases and 1664 hospital-based controls individually matched to the cases for age, sex, and district of residence. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using conditional logistic regression models. Among never-tobacco users, the ORs for the association between SHS and ESCC risk were above unity with ever exposure to SHS (OR = 1.32; 95% CI, 0.43-4.02) and exposure to SHS for > 14 h/wk (median value) (OR = 2.69; 95% CI, 0.75-20.65). In the analysis of data from all participants, the OR (95% CI) for the association between SHS and ESCC was (OR = 1.02; 95% CI, 0.53-1.93) for SHS ≤ 14 h/wk and (OR = 1.91; 95% CI, 0.75-4.89) for SHS >14 h/wk in the models adjusted for tobacco use and several other potential confounding factors. We found an indication of increased risk of ESCC associated with exposure to SHS. Studies with larger numbers of SHS-exposed never tobacco users are required to further examine this association.
Assuntos
Carcinoma de Células Escamosas/epidemiologia , Exposição Ambiental/estatística & dados numéricos , Neoplasias Esofágicas/epidemiologia , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Idoso , Estudos de Casos e Controles , Carcinoma de Células Escamosas do Esôfago , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Incidência , Índia/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Características de Residência , Fatores Sexuais , Fatores SocioeconômicosRESUMO
BACKGROUND: Esophageal cancer is one of the world's top ten cancers. Its incidence, especially in the form of squamous cell carcinoma, is very high in some Asian regions including Kashmir. Jammu Kashmir and Ladakh are three provinces of Jammu and Kashmir, the northern most state of India. The three regions represent ethnically diverse socio-cultural populations with different incidences of esophageal squamous cell carcinoma (ESCC), a suitable setting for epidemiological studies. Hence, comparing the lifestyle, dietary habits and gene pools between the three regions will help in elucidation of ESCC etiology further. Therefore, to assess the possibility of conducting a larger case control study, we carried out a feasibility study to identify the collaborators as well as to explore patient referral systems and available research facilities in the state. FINDINGS: We found conducting good cancer molecular epidemiology studies is difficult due to lack of proper research facilities and favourable administrative guidelines. The appropriate storage, transportation and analyses facilities of biological specimens for genome-wide association study and assessment of nutrition and exposure markers are unavailable or not sufficiently developed. Guidelines that can encourage scientific collaborations within the country seem unavailable. However, the administrative guidelines available under which the export of biological specimens out of India for analysis seems impossible. Consequently, Indian researchers are unable to collaborate with foreign scientists and render state of art research facilities inaccessible to them. Scientists in other parts of India may also confront with most of these impediments. CONCLUSION: The study found that for conducting conclusive molecular epidemiological studies in India, referral system in hospitals is not systematic, scientific research facilities are inadequate as well as the guidelines for foreign collaboration are not favourable.
RESUMO
Salt tea is the most commonly used beverage in Kashmir, India, where esophageal squamous cell carcinoma (ESCC) is the most common cancer. Salt tea is brewed in a unique way in Kashmir, usually with addition of sodium bicarbonate, which makes salt tea alkaline. As little information about the association between salt tea drinking and ESCC was available, we conducted a large-scale case-control study to investigate this association in Kashmir. We recruited 703 histologically confirmed cases of ESCC and 1664 controls individually matched to cases for age, sex, and district of residence. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Participants who consumed >1,250 ml day(-1) showed an increased risk of ESCC (OR = 2.60, 95% CIs = 1.68-4.02). Samovar (a special vessel for the beverage preparation) users (OR = 1.77, 95% CIs 1.25-2.50) and those who ate cereal paste with salt tea (OR = 2.14, 95% CIs = 1.55-2.94) or added bicarbonate sodium to salt tea (OR = 2.12, 95% CIs = 1.33-3.39) were at higher risk of ESCC than others. When analysis was limited to alkaline tea drinkers only, those who both consumed cereal paste with salt tea and used samovar vessel were at the highest risk (OR = 4.58, 95% CIs = 2.04-10.28). This study shows significant associations of salt tea drinking and some related habits with ESCC risk.
Assuntos
Carcinoma de Células Escamosas/etiologia , Neoplasias Esofágicas/etiologia , Chá/efeitos adversos , Idoso , Estudos de Casos e Controles , Cobre/administração & dosagem , Carcinoma de Células Escamosas do Esôfago , Feminino , Temperatura Alta , Humanos , Índia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
The study analyzed the relationship between genetic polymorphisms of phase I xenobiotic metabolizing enzymes, cytochromes P450 (CYP) 1A1 and CYP2E1 and esophageal squamous cell carcinoma (ESCC) in Kashmir, India. The different genotypes of CYP1A1 and CYP2E1 were analyzed by polymerase chain reaction and restriction fragment length polymorphism in 526 ESCC cases and equal number of matched controls. Conditional logistic regression models were used to assess the association of various genotypes with ESCC, gene-gene, and gene-environment interactions. High risk of ESCC was found in participants who carried CYP1A1 Val/Val genotype (OR=2.87; 95 % CI=1.00-8.44) and the risk increased in such individuals when c1/c1 of CYP2E1 genotype was also present (OR=5.68; 95 % CI=1.09-29.52). Risk due to CYP1A1 Val/Val genotype was further enhanced (OR=8.55; 95 % CI=1.86-42.20) when the analysis was limited to ever smokers. Participants who carried CYP2E1 c1/c2 genotype showed an inverse relation (OR=0.27; 95 % CI=0.17-0.43) with ESCC. The inverse association of CYP2E1 c1/c2 genotype was retained when CYP1A1 Ile/Ile was also present (OR=0.18; 95 % CI=0.09-0.32), as well as when analysis was limited to ever smokers (OR=0.45; 95 % CI=0.23-0.90). Significant interaction was found between CYP1A1 (Val/Val) and CYP2E1 (c1/c1) genotypes (OR=1.30; 95 % CI=1.12-1.51; P=0.001) and between CYP1A1 (Val/Val) and smoking (OR=1.31; 95 % CI=1.01-1.69; P=0.043). The study suggests CYP1A1 Val/Val and CYP2E1 c1/c1 genotypes are significantly associated with ESCC risk.
Assuntos
Carcinoma de Células Escamosas/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP2E1/genética , Neoplasias Esofágicas/genética , Idoso , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Esofágicas/epidemiologia , Carcinoma de Células Escamosas do Esôfago , Genótipo , Humanos , Incidência , Índia/epidemiologia , Pessoa de Meia-Idade , RiscoRESUMO
BACKGROUND: Several studies have reported association between animal contact and some cancer types, including lymphohaematopoietic, colon, pancreatic and neurological malignancies. We aimed to investigate the association between animal contact and risk of oesophageal squamous cell carcinoma (ESCC) in a case-control study in Kashmir, India, area with a relatively high incidence of ESCC. METHODS: We recruited 703 histologically confirmed ESCC cases and 1664 controls individually matched to the cases for age, sex and district of residence. Information, including on animal contact, was obtained in face-to-face interviews using a structured questionnaire. Conditional logistic regression models were used to calculate ORs and 95% CIs. RESULTS: As compared with no contact with animals, daily close contact was associated with an increased risk of ESCC (OR 5.99; 95% CI 3.86 to 9.31) in models adjusted for several potential confounding factors, including multiple indicators of socioeconomic status. This association persisted in subgroups following stratification by a composite wealth score and occupation. Irregular contact with animals was not associated with ESCC risk. The association between duration of animal contact and ESCC risk was mixed; however, contact for more than 50 years was associated with an increased risk (OR 3.10; 95% CI 1.53 to 6.26). Frequency (p for trend, 0.001) and duration (p for trend, <0.001) of animal contact showed dose-response association with ESCC risk. CONCLUSIONS: Our results suggest an association between long-term and daily close contact with animals and ESCC. This association needs to be investigated in further studies.
Assuntos
Criação de Animais Domésticos , Carcinoma de Células Escamosas/etiologia , Exposição Ambiental/efeitos adversos , Neoplasias Esofágicas/etiologia , Gado , Idoso , Animais , Estudos de Casos e Controles , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Índia , Entrevistas como Assunto , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Ocupações , Fatores de Risco , Classe Social , Inquéritos e Questionários , Fatores de TempoRESUMO
Studies have persistently associated esophageal squamous cell carcinoma (ESCC) risk with low socioeconomic status (SES), but this association is unexplored in Kashmir, an area with a high incidence of ESCC in the northernmost part of India. We carried out a case-control study to assess the association of multiple indicators of SES and ESCC risk in the Kashmir valley. A total number of 703 histologically confirmed ESCC cases and 1664 controls matched to the cases for age, sex, and district of residence were recruited from October 2008 to January 2012. Conditional logistic regression models were used to calculate unadjusted and adjusted odds ratios and 95% confidence intervals. Composite wealth scores were constructed based on the ownership of several appliances using multiple correspondence analyses. Higher education, living in a kiln brick or concrete house, use of liquefied petroleum gas and electricity for cooking, and higher wealth scores all showed an inverse association with ESCC risk. Compared to farmers, individuals who had government jobs or worked in the business sector were at lower risk of ESCC, but this association disappeared in fully adjusted models. Occupational strenuous physical activity was strongly associated with ESCC risk. In summary, we found a strong relationship of low SES and ESCC in Kashmir. The findings need to be studied further to understand the mechanisms through which such SES parameters increase ESCC risk.