[Show abstract][Hide abstract] ABSTRACT: A strong association between smoking and SCLC is noted whereas the dose–response relationships are less clear. We demonstrate that cumulative smoking of the first 50 pack-years is associated with a sharper increase in SCLC risk. Moreover, although the relationship between smoking and COPD or COPD and SCLC is well-established, no study has investigated the causal pathway among smoking, COPD, and SCLC. Here we reveal the risks of smoking behaviors on SCLC which are partially mediated (up to 7.6%) through COPD. The findings warrant further experimental study to elucidate the mechanisms in this causal pathway.
[Show abstract][Hide abstract] ABSTRACT: Most mouthwashes contain alcohol, a known cause of head and neck cancer (oral cavity, pharynx, larynx), likely through the carcinogenic activity of acetaldehyde, formed in the oral cavity from alcohol. We carried out a pooled analysis of 8981 cases of head and neck cancer and 10 090 controls from 12 case-control studies with comparable information on mouthwash use in the International Head and Neck Cancer Epidemiology Consortium. Logistic regression was used to assess the association of mouthwash use with cancers of the oral cavity, oropharynx, hypopharynx, and larynx, adjusting for study, age, sex, pack-years of tobacco smoking, number of alcoholic drinks/day, and education. Compared with never users of mouthwash, the odds ratio (OR) of all head and neck cancers was 1.01 [95% confidence interval (CI): 0.94-1.08] for ever users, based on 12 studies. The corresponding ORs of cancer of the oral cavity and oropharynx were 1.11 (95% CI: 1.00-1.23) and 1.28 (95% CI: 1.06-1.56), respectively. OR for all head and neck cancer was 1.15 (95% CI: 1.01-1.30) for use for more than 35 years, based on seven studies (P for linear trend=0.01), and OR 1.31 (95% CI: 1.09-1.58) for use more than one per day, based on five studies (P for linear trend <0.001). Although limited by the retrospective nature of the study and the limited ability to assess risks of mouthwash use in nonusers of tobacco and alcohol, this large investigation shows potential risks for head and neck cancer subsites and in long-term and frequent users of mouthwash. This pooled analysis provides the most precise estimate of the association between mouthwash use and head and neck cancer.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 08/2015; DOI:10.1097/CEJ.0000000000000179 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dear Dr. Rowland,Please accept our response to Dr. Frederick Guilford’s comments of November 17, 2014, regarding our recent article which appeared in your Journal .The main issue described by Dr. Guilford refers to a published paper  referenced in the discussion section of our paper (reference #68). We cited that paper as an example of an in vitro study where intact GSH was shown to be more effective than N-acetylcysteine in “restoring immune function in macrophages from HIV-infected individuals” . Indeed, Dr. Guilford is correct in that the GSH preparation used in that study was a liposome encapsulated GSH obtained from his company as opposed to the non-encapsulated form used in our study. However, I would like to emphasize that our study was not designed to test the relative efficacy of different GSH preparations, including liposomal GSH, but rather to determine the impact of GSH supplementation alone on GSH levels in blood and exfoliated buccal cells.We disagree with Dr. Gu ...
European Journal of Nutrition 03/2015; 54(5). DOI:10.1007/s00394-015-0873-6 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A critical component of the US Food and Drug Administration's new authority to regulate tobacco products is understanding communications and marketing of tobacco products and their perceived risks in different geographic, age, race, ethnic and socioeconomic groups. Such information might be particularly useful in subgroups of the population or geographic areas that experience high tobacco use and suffer a disproportionate burden from tobacco-related diseases. For certain populations, there may be additional cultural factors unique to the geographical region which may promote smoking behavior. The purpose of the present study was to examine the perceptions of tobacco-related media messages among a sample of rural Appalachian natives, a population with smoking rates higher than the national average and who are disproportionately affected by tobacco-related and other cancers.
A series of four focus group sessions were conducted in a north-central area of Pennsylvania, in one of 52 counties in Pennsylvania designated as within the Appalachian region. Participants were recruited via direct mail letters, advertisements in a local newspaper, and recruiting flyers posted at the local library. The focus groups were moderated by trained professional staff from The Pennsylvania State University's Center for Survey Research (CSR). Focus group sessions sought to examine perceptions of tobacco-related media in an Appalachian region of Pennsylvania. The sessions were audiotaped and transcribed, and the data was analyzed using qualitative approaches.
Participants reported that pro-tobacco ads and favorable messages were received through the internet, direct mail, convenience stores, billboards, movies, and other sources. Anti-tobacco messages were identified primarily from television and magazines. In general, participants concluded that quitting was a matter of choice and was not influenced by pro- or anti-tobacco media.
These results indicate that both pro- and anti-tobacco messages from a variety of sources are highly recognized and remembered in detail in Appalachia, but the effectiveness of anti-tobacco messages is questionable within this group. It was found that, without exception, group members reported that no media messages - either pro- or anti-tobacco - had any meaningful impact on their current behavior. Group members did, however, recognize that media messages influenced their behavior at the time they were first starting to smoke. The failure of these messages to connect with this population may reflect the lack of specific tailoring of messages to fit the distinct culture and values of this Appalachian population.
Rural and remote health 03/2015; 15(1):3136. · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The HFE (high iron) protein plays a key role in the regulation of body iron. HFE polymorphisms (H63D and C282Y) are the common genetic variants in Caucasians. Based on frequency data, both HFE polymorphisms have been associated with increased risk in a number of cancers. The prevalence of the two major HFE polymorphisms in a human brain tumor patient populations and the impact of HFE polymorphisms on survival have not been studied. In the present study, there is no overall difference in survival by HFE genotype. However, male GBM patients with H63D HFE (H63D) have poorer overall survival than wild type HFE (WT) male GBM (p = 0.03). In GBM patients with the C282Y HFE polymorphism (C282Y), female patients have poorer survival than male patients (p = 0.05). In addition, female metastatic brain tumor patients with C282Y have shorter survival times post diagnosis than WT patients (p = 0.02) or male metastatic brain tumor patients with C282Y (p = 0.02). There is a tendency toward a lower proportion of H63D genotype in GBM patients than a non-tumor control group (p = 0.09) or other subtypes of brain tumors. In conclusion, our study suggests that HFE genotype impacts survival of brain tumor patients in a gender specific manner. We previously reported that glioma and neuroblastoma cell lines with HFE polymorphisms show greater resistance to chemo and radiotherapy. Taken together, these data suggest HFE genotype is an important consideration for evaluating and planning therapeutic strategies in brain tumor patients.
Journal of Neuro-Oncology 12/2014; 122(1). DOI:10.1007/s11060-014-1681-1 · 3.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications.
Patients and methods:
We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates.
Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years).
This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.
Annals of Oncology 07/2014; 25(10). DOI:10.1093/annonc/mdu276 · 7.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: UDP-glucuronosyltransferases (UGTs) play an important role in the phase II metabolism of exogenous and endogenous compounds. As colorectal cancer (CRC) etiology is thought to involve the biotransformation of dietary factors, UGT polymorphisms may affect CRC risk by altering levels of exposure. Genotyping of over 1800 Caucasian subjects was completed to identify the role of genetic variation in nine UGT1A and five UGT2B genes on CRC risk. Unconditional logistic regression and haplotype analyses were conducted to identify associations with CRC risk and potential gene-environment interactions. UGT1A haplotype analysis found that the T-G haplotype in UGT1A10 exon 1 (block 2: rs17864678, rs10929251) decreased cancer risk for the colon [proximal (OR = 0.28, 95% CI = 0.11–0.69) and for the distal colon (OR = 0.32, 95% CI = 0.12–0.91)], and that the C-T-G haplotype in the 3′ region flanking the UGT1A shared exons (block 11: rs7578153, rs10203853, rs6728940) increased CRC risk in males (OR = 2.56, 95% CI = 1.10–5.95). A haplotype in UGT2B15 containing a functional variant (rs4148269, K523T) and an intronic SNP (rs6837575) was found to affect rectal cancer risk overall (OR = 2.57, 95% CI = 1.21–5.04) and in females (OR = 3.08, 95% CI = 1.08–8.74). An interaction was found between high NSAID use and the A-G-T haplotype (block 10: rs6717546, rs1500482, rs7586006) in the UGT1A shared exons that decreased CRC risk. This suggests that UGT genetic variation alters CRC risk differently by anatomical sub-site and gender and that polymorphisms in the UGT1A shared exons may have a regulatory effect on gene expression that allows for the protective effect of NSAIDs on CRC risk.
Genes Chromosomes and Cancer 06/2014; 53(6):454-66. DOI:10.1002/gcc.22157 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Glutathione (GSH), the most abundant endogenous antioxidant, is a critical regulator of oxidative stress and immune function. While oral GSH has been shown to be bioavailable in laboratory animal models, its efficacy in humans has not been established. Our objective was to determine the long-term effectiveness of oral GSH supplementation on body stores of GSH in healthy adults.
A 6-month randomized, double-blinded, placebo-controlled trial of oral GSH (250 or 1,000 mg/day) on GSH levels in blood, erythrocytes, plasma, lymphocytes and exfoliated buccal mucosal cells was conducted in 54 non-smoking adults. Secondary outcomes on a subset of subjects included a battery of immune markers.
GSH levels in blood increased after 1, 3 and 6 months versus baseline at both doses. At 6 months, mean GSH levels increased 30-35 % in erythrocytes, plasma and lymphocytes and 260 % in buccal cells in the high-dose group (P < 0.05). GSH levels increased 17 and 29 % in blood and erythrocytes, respectively, in the low-dose group (P < 0.05). In most cases, the increases were dose and time dependent, and levels returned to baseline after a 1-month washout period. A reduction in oxidative stress in both GSH dose groups was indicated by decreases in the oxidized to reduced glutathione ratio in whole blood after 6 months. Natural killer cytotoxicity increased >twofold in the high-dose group versus placebo (P < 0.05) at 3 months.
These findings show, for the first time, that daily consumption of GSH supplements was effective at increasing body compartment stores of GSH.
European Journal of Nutrition 05/2014; 54(2). DOI:10.1007/s00394-014-0706-z · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gastric cancer affects about one million people per year worldwide, being the second leading cause of cancer mortality. The study of its etiology remains therefore a global issue as it may allow the identification of major targets, besides eradication of Helicobacter pylori infection, for primary prevention. It has however received little attention, given its comparatively low incidence in most high-income countries. We introduce a consortium of epidemiological investigations named the 'Stomach cancer Pooling (StoP) Project'. Twenty-two studies agreed to participate, for a total of over 9000 cases and 23 000 controls. Twenty studies have already shared the original data set. Of the patients, 40% are from Asia, 43% from Europe, and 17% from North America; 34% are women and 66% men; the median age is 61 years; 56% are from population-based case-control studies, 41% from hospital-based ones, and 3% from nested case-control studies derived from cohort investigations. Biological samples are available from 12 studies. The aim of the StoP Project is to analyze the role of lifestyle and genetic determinants in the etiology of gastric cancer through pooled analyses of individual-level data. The uniquely large data set will allow us to define and quantify the main effects of each risk factor of interest, including a number of infrequent habits, and to adequately address associations in subgroups of the population, as well as interaction within and between environmental and genetic factors. Further, we will carry out separate analyses according to different histotypes and subsites of gastric cancer, to identify potential different risk patterns and etiological characteristics.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 02/2014; 24(1). DOI:10.1097/CEJ.0000000000000017 · 3.03 Impact Factor