Esophageal cancer in relation to alcohol drinking and tobacco use among men in Kerala, India - Karunagappally cohort.

BACKGROUND: In the Karunagappally cohort, esophageal cancer is the third most common cancer with an age-adjusted incidence rate of 6.2 per 100,000 person-years among men. The present study analyzed the risk of esophageal cancer in relation to alcohol drinking and tobacco use. METHODS: The study included 65,528 men aged 30-84 years in the Karunagappally cohort, India. RESULTS: Poisson regression analysis showed that alcohol drinking significantly increased (P = 0.027) the risk of esophageal cancer and the relative risk (RR) for current drinkers was 1.6, (95 % confidence interval (CI) = 1.1-2.3). The risk increased significantly in heavy alcohol drinkers (250 g of ethanol or above per day) (RR = 2.1, 95 % CI = 1.2-3.5) (P for trend = 0.014) and among current arrack consumers (RR = 1.8, 95 % CI = 0.99-3.29) (P for trend = 0.025). Current bidi and cigarette smokers showed an increase in the trend of cancer risk. A significantly higher risk was seen in those who had started smoking bidi before the age of 18 years, RR = 1.9 (95 % CI = 1.1-3.3) (P for trend = 0.044). Furthermore, increased RR for heavy bidi and cigarette smokers were 1.6 (95 % CI = 1.1-2.5) and 2.4 (95 % CI = 1.3-4.5), respectively. CONCLUSION: To the best of our knowledge, this is the first cohort study in India to report an increased esophageal cancer risk with respect to alcohol drinking.

Inorganic mercury-induced MIP-2 expression is suppressed by N-acetyl-L-cysteine in RAW264.7 macrophages.

Macrophages play an important role in neurotoxicity caused by methylmercury exposure through inflammatory responses. Methylmercury is known to demethylate to inorganic mercury in the brain, and macrophages are likely to be involved in this process. However, the inflammatory responses of macrophages against exposure to inorganic mercury are unclear. In the present study, inflammatory cytokine expression profiles were examined in the presence of non-toxic doses of inorganic mercury (Hg2+) using RAW264.7 macrophages, focusing on the expression of C-X-C motif chemokine 2 (MIP-2)/platelet-derived growth factor-inducible protein KC (KC) and C-C motif chemokine 12 (MCP-5). Furthermore, the suppressive effect of N-acetyl-L-cysteine (NAC) on inorganic mercury-induced MIP-2 expression was also examined. Inorganic mercury-induced mRNA expression was measured using reverse transcription-quantitative PCR. The mRNA expression of MIP-2 and MCP-5 was significantly upregulated by exposure to 20 µM Hg2+ (non-toxic levels), but not that of KC. The suppressive effect of NAC on these cytokine expression levels was examined by its addition to the culture medium together with Hg2+ (co-treatment), and pre- and post-treatments in which the cells were treated with NAC before and after Hg2+ exposure, respectively. Hg2+-upregulated MIP-2 expression was suppressed by NAC regardless of the time sequence of the treatment, suggesting that the suppressive role of NAC in Hg2+-induced inflammation manifests as a possible chelator and antioxidant/reactive oxygen species scavenger.

Thyroid nodule prevalence among women in areas of high natural background radiation, Karunagappally, Kerala, India.

PURPOSE: Radiation exposure has been reported to cause thyroid nodules. The study area was Karunagapally, which has several areas with high natural radiation levels derived from thorium and its decay products. Since thyroid abnormalities are more common in women, the focus was only on women. METHODS: The examinations included interview, ultrasonography of the thyroid and serum assays of free thyroxine (FT4), thyrotropin (TSH), and anti-thyroglobulin levels. Cumulative dose during the childhood and lifetime cumulative dose (lagged by 5 years) were estimated. RESULTS: We examined 524 female residents aged 17-73 years and found 75 cases of solitary solid thyroid nodules. The prevalence of thyroid nodules were 14.1 % (n = 42) in high dose panchayats and 14.5% (n = 33) in low-dose panchayats. In the logistic regression analysis adjusted for age, the prevalence of solitary thyroid nodule was not linearly related to childhood cumulative dose (P for trend = 0.159) and lifetime cumulative dose (P for trend = 0.333). The prevalence of thyroiditis and hypothyroidism was not related to natural radiation exposure. Serum levels of FT4 or TSH were not related to natural radiation exposure. CONCLUSIONS: The results obtained from the present study do not support the increase of solitary thyroid nodule, thyroiditis or hypothyroidism in relation to high-natural-background-radiation exposure.

Suppression of methylmercury-induced MIP-2 expression by N-acetyl-L-cysteine in murine RAW264.7 macrophage cell line.

BACKGROUND: The aim of this study is to examine the inflammatory-cytokine expressions in the presence of non-cytotoxic dose of methylmercury (MeHg) in murine macrophages, which is suspected to play an important role in brain damage caused by MeHg exposure. We focused on murine macrophage inflammatory protein-2 (MIP-2), keratinocyte chemoattractant (KC), and monocyte chemoattractant protein-5 (MCP-5). MIP-2 and KC are murine functional homologues of human IL-8 and MCP-5 for human MCP-1. Furthermore, we examined the suppressive effect of N-acetyl-L-cysteine (NAC) on the MeHg-induced inflammatory cytokines. METHODS: In a murine RAW264.7 macrophage cell line, MeHg-induced cytokine expressions were measured using real-time PCR. The suppressive effect of NAC was examined by putting it into the culture medium together with MeHg (co-treatment). In addition, pre- and post-treatment experiments were conducted, in which the cells were treated with NAC before and after MeHg exposure, respectively. RESULTS: Exposure to a non-cytotoxic dose of MeHg up-regulated the mRNA expression of MIP-2 and MCP-5. On the other hand, KC expression was not induced in the presence of MeHg. Effect of MeHg on MIP-2 expressions was suppressed by pre-, co-, and post-treatment with NAC. However, the suppressive effect of pre-treatment was less than the post-treatment, which was as effective as co-treatment. CONCLUSION: In functional homologues of human IL-8, only MIP-2 expression, not KC, was activated in the presence of non-cytotoxic dose of MeHg in murine RAW264.7 macrophage cell line. The more evident inhibitory effect of NAC observed in post-treatment experiments suggests a possible involvement of intracellular activities such as antioxidant effects.

Radiation-induced Epstein-Barr virus reactivation in gastric cancer cells with latent EBV infection.

Epstein-Barr virus, a ubiquitous human herpes virus with oncogenic activity, can be found in 6%-16% of gastric carcinomas worldwide. In Epstein-Barr virus-associated gastric carcinoma, only a few latent genes of the virus are expressed. Ionizing irradiation was shown to induce lytic Epstein-Barr virus infection in lymphoblastoid cell lines with latent Epstein-Barr virus infection. In this study, we examined the effect of ionizing radiation on the Epstein-Barr virus reactivation in a gastric epithelial cancer cell line (SNU-719, an Epstein-Barr virus-associated gastric carcinoma cell line). Irradiation with X-ray (dose = 5 and 10 Gy; dose rate = 0.5398 Gy/min) killed approximately 25% and 50% of cultured SNU-719 cells, respectively, in 48 h. Ionizing radiation increased the messenger RNA expression of immediate early Epstein-Barr virus lytic genes (BZLF1 and BRLF1), determined by real-time reverse transcription polymerase chain reaction, in a dose-dependent manner at 48 h and, to a slightly lesser extent, at 72 h after irradiation. Similar findings were observed for other Epstein-Barr virus lytic genes (BMRF1, BLLF1, and BcLF1). After radiation, the expression of transforming growth factor beta 1 messenger RNA increased and reached a peak in 12-24 h, and the high-level expression of the Epstein-Barr virus immediate early genes can convert latent Epstein-Barr virus infection into the lytic form and result in the release of infectious Epstein-Barr virus. To conclude, Ionizing radiation activates lytic Epstein-Barr virus gene expression in the SNU-719 cell line mainly through nuclear factor kappaB activation. We made a brief review of literature to explore underlying mechanism involved in transforming growth factor beta-induced Epstein-Barr virus reactivation. A possible involvement of nuclear factor kappaB was hypothesized.

Waterpipe Tobacco Smoking and Gastric Cancer Risk among Vietnamese Men.

BACKGROUND: The association of waterpipe tobacco (WPT) smoking with gastric cancer (GC) risk was suggested. METHODS: A hospital-based case-control study was conducted to examine the association of WPT with GC risk among Vietnamese men, in Hanoi city, during the period of 2003-2011. Newly-diagnosed GC cases (n = 454) and control patients (n = 628) were matched by age (+/- 5 years) and the year of hospitalization. Information on smoking and alcohol drinking habits and diet including salty food intake and fruits/vegetables consumption were obtained by the interview. Maximum likelihood estimates of odds ratios (ORs) and corresponding 95% confidence intervals (Cis) were obtained using conditional logistic regression models. RESULTS: The group with the highest consumption of citrus fruits showed a significantly low GC risk (OR = 0.6, 95%CI = 0.4-0.8, P for trend = 0.002). However, there was no association of raw vegetable consumption with GC risk. Referring to never smokers, GC risk was significantly higher in current WPT smokers (OR = 1.8, 95%CI = 1.3-2.4), and it was more evident in exclusively WPT smokers (OR = 2.7, 95%CI = 1.2-6.5). GC risk tended to be higher with daily frequency and longer duration of WPT smoking but these trends were not statistically significant (P for trend: 0.144 and 0.154, respectively). GC risk of those who started smoking WPT before the age of 25 was also significantly high (OR = 3.7, 95%CI = 1.2-11.3). Neither cigarette smoking nor alcohol drinking was related to GC risk. CONCLUSION: The present findings revealed that WPT smoking was positively associated with GC risk in Vietnamese men.

Cytotoxic effects of NF­κB inhibitors in combination with anti­herpes agents on Epstein­Barr virus­positive gastric carcinoma in vitro.

Epstein-Barr virus (EBV) infection in tumor cells is usually restricted to the latent form, indicating that the induction of viral lytic infection may present a novel approach for the treatment of EBV­associated tumors. By contrast, EBV lytic replication is inhibited by high­levels of nuclear factor (NF)­κB, which suggests that NF­κB inhibitors may activate lytic replication from the latent form. In the current study, the addition of NF­κB inhibitors (Bay11­7082, Z­LLF­CHO and aspirin) was observed to induce the EBV lytic genes BZLF1, BRLF1 and BMRF1 in EBV­positive gastric cancer (GC) cells. Both EBV­positive and ­negative GC cells were treated with different concentrations of anti­herpes agents and the cytotoxic effects were measured at different time points following induction of EBV lytic replication. A marginal dose­ and time­dependent reduction in cell viability was observed for EBV­positive and­negative GC cells. The cytotoxic effects of NF­κB inhibitors on EBV­positive GC cells were enhanced by the addition of the anti­herpes agents, ganciclovir, acyclovir, foscarnet and brivudine (P<0.05). However, there was no significant synergistic effect on EBV­negative GC cells. The combination of 5 mM aspirin and ganciclovir exhibited the highest cytotoxic effect in EBV­positive GC cells (CC50=7.2 µg/ml).

Gastric cancer risk in relation to tobacco use and alcohol drinking in Kerala, India--Karunagappally cohort study.

AIM: To assess the risk of gastric cancer (GC) in relation to tobacco use and alcohol drinking in the Karunagappally cohort in Kerala, South India. METHODS: This study examined the association of tobacco use and alcohol drinking with GC incidence among 65553 men aged 30-84 in the Karunagappally cohort. During the period from 1990-2009, 116 GC cases in the cohort were identified as incident cancers. These cases were identified from the population-based cancer registry. Information regarding risk factors such as socioeconomic factors and tobacco and alcohol habits of cohort members were collected from the database of the baseline survey conducted during 1990-1997. The relative risks (RRs) and the corresponding 95% confidence intervals (95%CIs) for tobacco use were obtained from Poisson regression analysis of grouped survival data, considering age, follow-up period, occupation and education. RESULTS: Bidi smoking was associated with GC risk (P = 0.042). The RR comparing current versus never smokers was 1.6 (95%CI: 1.0-2.5). GC risk was associated with the number of bidis smoked daily (P = 0.012) and with the duration of bidi smoking (P = 0.036). Those who started bidi smoking at younger ages were at an elevated GC risk; the RRs for those starting bidi smoking under the age of 18 and ages 18-22 were 2.0 (95%CI: 1.0-3.9) and 1.8 (95%CI: 1.1-2.9), respectively, when their risks were compared with lifetime non-smokers of bidis. Bidi smoking increased the risk of GC among never cigarette smokers more evidently (RR = 2.2; 95%CI: 1.3-4.0). GC risk increased with the cumulative amount of bidi smoking, which was calculated as the number of bidis smoked per day x years of smoking (bidi-year; P = 0.017). Cigarette smoking, tobacco chewing or alcohol drinking was not significantly associated with GC risk. CONCLUSION: Among a male cohort in South India, gastric cancer risk increased with the number and duration of bidi smoking.

Associations of tobacco use and alcohol drinking with laryngeal and hypopharyngeal cancer risks among men in Karunagappally, Kerala, India -Karunagappally cohort study.

BACKGROUND: From among a cohort of 65,553 men aged 30-84 in Karunagappally Taluk, Kerala, India, 52 hypopharyngeal cancer cases and 85 laryngeal cancer cases were identified by the Karunagappally Cancer Registry during the period between 1990 and 2009. METHODS: We conduct Poisson regression analysis of grouped data, taking into account age and education. RESULTS: This study showed that the incidence rates of cancers of the hypopharynx and the larynx were strongly related to the number of bidis smoked a day (P<0.001 for both hypopharyngeal and laryngeal cancers) and duration of bidi smoking (P=0.009; P<0.001). Laryngeal cancer risk was significantly increased by bidi smoking (P<0.001), cigarette smoking (P=0.013) and regular alcohol use (P=0.005). CONCLUSION: The present study, the first cohort study to examine the association of hypopharyngeal and laryngeal cancer incidence rates with bidi smoking in South Asia, clearly showed dose-response relationships between those cancer risks and bidi smoking; larger amounts of bidi smoked a day and longer durations of bidi smoking increased the incidence rates of those cancers. Tobacco chewing was found not related to the risk of hypopharynx or larynx cancer.