Biomedical subjects

Philip R Taylor

Publications and source records attributed to Philip R Taylor.

At least 37 records · Page 2Linked to original sources

PubMed2006

Iron and colorectal cancer risk in the alpha-tocopherol, beta-carotene cancer prevention study.

In vitro and in vivo studies have associated iron with both the initiation and promotional stages of carcinogenesis. We investigated whether iron was associated with colorectal cancer in a nested case-control study within the alpha-tocopherol, beta-carotene cancer prevention study cohort. Exposure was assessed at baseline, using a 276-item food frequency questionnaire and a fasting serum sample. The study included 130 colorectal cancer cases (73 colon cancers and 57 rectal cancers) and 260 controls. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Supplemental iron intake was only reported for 4 cases and 18 controls; therefore, we were unable to obtain meaningful results for this variable. Comparing the highest to the lowest quartiles, there was an inverse association between serum ferritin and colorectal cancer risk (OR = 0.4, 95% CI = 0.2-0.9) and a suggestion of an inverse association between dietary iron and colorectal cancer risk (OR = 0.4, 95% CI = 0.1-1.1). In addition, serum ferritin, serum iron and transferrin saturation were all inversely associated with colon cancer risk specifically (OR = 0.2, 95% CI = 0.1-0.7, p trend = 0.02; OR = 0.2, 95% CI = 0.1-0.9, p trend = 0.05; OR = 0.1, 95% CI = 0.02-0.5, p trend = 0.003, respectively), whereas serum unsaturated iron binding capacity was positively associated with colon cancer risk (OR = 4.7, 95% CI = 1.4-15.1, p trend = 0.009). In summary, we found a significant inverse association between several serum iron indices and colon cancer risk.

Adult↗

PubMed2006

Higher urine 1-hydroxy pyrene glucuronide (1-OHPG) is associated with tobacco smoke exposure and drinking maté in healthy subjects from Rio Grande do Sul, Brazil.

BACKGROUND: The highest rates of esophageal squamous cell carcinoma (ESCC) in Brazil occur in Rio Grande do Sul, the most southern state, which has incidence rates of 20.4/100,000/year for men and 6.5/100,000/year for women. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) through tobacco smoke and other sources may increase the risk of ESCC. The aims of the current study were to investigate the degree and sources of PAH exposure of the inhabitants of this region of southern Brazil. METHODS: Two hundred healthy adults (half smokers, half non smokers, half male and half female) were recruited, given a standardized questionnaire, and asked to provide a urine sample for measurement of 1-hydroxypyrene glucuronide (1-OHPG), a PAH metabolite). Urine 1-OHPG concentrations were measured using immunoaffinity chromatography and synchronous fluorescence spectroscopy and urine cotinine was measured using a dipstick test. We examined factors associated with 1-OHPG concentration using Wilcoxon tests and multiple linear regression. RESULTS: Urine 1-hydroxypyrene glucuronide (1-OHPG) was successfully measured on 199 subjects. The median (interquartile range) of urine 1-OHPG in the 199 participants was 2.09 pmol/mL (0.51, 5.84). Tobacco smoke exposure and maté drinking were statistically significantly associated with higher urine 1-OHPG concentrations in the multivariate linear regression model. CONCLUSION: Tobacco smoke and maté both contribute to high levels of benzo[a]pyrene exposure in the people of southern Brazil. This high PAH exposure may contribute to the high rates of ESCC observed in this population. The increased urine 1-OHPG concentrations associated with maté suggest that contaminants, not just thermal injury, may help explain the increased risk of ESCC previously reported for maté consumption.

Alcohol Drinking↗

PubMed2006

Expression of functionally different dectin-1 isoforms by murine macrophages.

Dectin-1 is a specific receptor for beta-glucans and a major receptor for fungal particles on macrophages (Mphi). It is a type II membrane receptor that has a C-terminal, NK-like, C-type lectin-like domain separated from the cell membrane by a short stalk region and a cytoplasmic immunoreceptor tyrosine-based activation-like motif. We observed functional differences in dectin-1-dependent recognition of fungal particles by Mphi from different mouse strains. RT-PCR analysis revealed that mice have at least two splice forms of dectin-1, generated by differential usage of exon 3, encoding the full-length dectin-1A and a stalkless Mphi dectin-1B. Mphi from BALB/c mice and genetically related mice expressed both isoforms in similar amounts, whereas Mphi from C57BL/6 and related mice mainly expressed the smaller isoform. NIH-3T3 fibroblast and RAW264.7 macrophage cell lines stably expressing either isoform were able to bind and phagocytose zymosan at 37 degrees C. However, binding by the smaller dectin-1B isoform was significantly affected at lower temperatures. These properties were shared by the equivalent human isoforms. The relative ability of each of the isoforms to induce TNF-alpha production in RAW264.7 Mphi was also found to be different. These results are the first evidence that dectin-1 isoforms are functionally distinct and indicate that differential isoform usage may represent a mechanism of regulating cellular responses to beta-glucans.

Animals↗

PubMed2006

Real-time telomerase assay of less-invasively collected esophageal cell samples.

Genomic and proteomic efforts have discovered a complex list of biomarkers that identify human disease, stratify risk of disease within populations, and monitor drug or therapy responses for treatment. Attention is needed to characterize these biomarkers and to develop high-throughput technologies to evaluate their accuracy and precision. Telomerase activity is correlated with tumor progression, indicating cells that express telomerase possess aggressive clinical behavior and that telomerase activity could be a clinically important cancer biomarker. Traditionally, the detection of cancer has involved invasive procedures to procure samples. There is a need for less invasive approaches suitable for population- and clinic-based assays for cancer early detection. Esophageal balloon cytology (EBC) is a low-invasive screening technique, which samples superficial epithelial cells from the esophagus. Since telomerase activity is absent in superficial cells of normal esophageal squamous epithelium but is often present in superficial cells from dysplastic lesions and ESCCs, measuring telomerase activity in EBC samples may be a good way to screen for these lesions. The development of rapid real-time telomerase activity assays raises the possibility of extending such screening to high-risk populations. In this study, we evaluate the feasibility of using rapid Real-Time Telomerase Repeat Amplification Protocol (RTTRAP) for the analysis of NIST telomerase candidate reference material and esophageal clinical samples. The telomerase activity of eight EBC samples was also measured by capillary electrophoresis of RTTRAP products, RApidTRAP, and hTERT mRNA RT-PCR assays. These findings demonstrate the feasibility of using the RTTRAP assay in EBC samples and suggest that individuals from high-risk populations can be screened for telomerase activity.

Biomarkers, Tumor↗

PubMed2006

A prospective study of serum C-reactive protein and colorectal cancer risk in men.

Chronic inflammation has been implicated in the etiology of colorectal cancer. C-reactive protein (CRP), a sensitive marker of inflammation, has been investigated with regard to colorectal cancer in only three previous studies, and the results from these investigations were inconsistent. We examined serum CRP levels in relation to colorectal cancer incidence in a nested case-control study within the Alpha Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 Finnish males enrolled from 1985 to 1988 with follow-up through April 2002. Colorectal cancer cases were ascertained by the Finnish Cancer Registry; this analysis included 130 cases of colorectal cancer (with available blood), which occurred between 1990 and April 30, 2002, and 260 matched controls. Baseline median CRP levels were approximately 25% higher among colorectal cancer cases (3.4 mg/L) than controls (2.6 mg/L; P = 0.04). Relative to men in the lowest quartile of CRP concentration, men in the highest quartile had an odds ratio of 2.9 (95% confidence interval, 1.4-6.0) for developing colorectal cancer with a dose-response relationship supported (P(trend) = 0.006). The relation between CRP and incident colorectal cancer was modified by body mass index such that the association was stronger among lean individuals than in heavier individuals (P(interaction) = 0.018). These results support the notion that chronic low-grade inflammation is a marker for increased risk of colorectal cancer.

Body Mass Index↗

PubMed2006

The carbohydrate-recognition domain of Dectin-2 is a C-type lectin with specificity for high mannose.

We examined the carbohydrate-binding potential of the C-type lectin-like receptor Dectin-2 (Clecf4n). The carbohydrate-recognition domain (CRD) of Dectin-2 exhibited cation-dependent mannose/fucose-like lectin activity, with an IC(50) for mannose of approximately 20 mM compared to an IC(50) of 1.5 mM for the macrophage mannose receptor when assayed by similar methodology. The extracellular domain of Dectin-2 exhibited binding to live Candida albicans and the Saccharomyces-derived particle zymosan. This binding was completely abrogated by cation chelation and was competed by yeast mannans. We compared the lectin activity of Dectin-2 with that of two other C-type lectin receptors (mannose receptor and SIGNR1) known to bind fungal mannans. Both mannose receptor and SIGNR1 were able to bind bacterial capsular polysaccharides derived from Streptococcus pneumoniae, but interestingly they exhibited distinct binding profiles. The Dectin-2 CRD exhibited only weak interactions to some of these capsular polysaccharides, indicative of different structural or affinity requirements for binding, when compared with the other two lectins. Glycan array analysis of the carbohydrate recognition by Dectin-2 indicated specific recognition of high-mannose structures (Man(9)GlcNAc(2)). The differences in the specificity of these three mannose-specific lectins indicate that mannose recognition is mediated by distinct receptors, with unique specificity, that are expressed by discrete subpopulations of cells, and this further highlights the complex nature of carbohydrate recognition by immune cells.

Binding, Competitive↗

PubMed2006

Regulation of cytosolic phospholipase A2 activation and cyclooxygenase 2 expression in macrophages by the beta-glucan receptor.

Phagocytosis of non-opsonized microorganisms by macrophages initiates innate immune responses for host defense against infection. Cytosolic phospholipase A(2) is activated during phagocytosis, releasing arachidonic acid for production of eicosanoids, which initiate acute inflammation. Our objective was to identify pattern recognition receptors that stimulate arachidonic acid release and cyclooxygenase 2 (COX2) expression in macrophages by pathogenic yeast and yeast cell walls. Zymosan- and Candida albicans-stimulated arachidonic acid release from resident mouse peritoneal macrophages was blocked by soluble glucan phosphate. In RAW264.7 cells arachidonic acid release, COX2 expression, and prostaglandin production were enhanced by overexpressing the beta-glucan receptor, dectin-1, but not dectin-1 lacking the cytoplasmic tail. Pure particulate (1, 3)-beta-D-glucan stimulated arachidonic acid release and COX2 expression, which were augmented in a Toll-like receptor 2 (TLR2)-dependent manner by macrophage-activating lipopeptide-2. However, arachidonic acid release and leukotriene C(4) production stimulated by zymosan and C. albicans were TLR2-independent, whereas COX2 expression and prostaglandin production were partially blunted in TLR2(-/-) macrophages. Inhibition of Syk tyrosine kinase blocked arachidonic acid release and COX2 expression in response to zymosan, C. albicans, and particulate (1, 3)-beta-D-glucan. The results suggest that cytosolic phospholipase A(2) activation triggered by the beta-glucan component of yeast is dependent on the immunoreceptor tyrosine-based activation motif-like domain of dectin-1 and activation of Syk kinase, whereas both TLR2 and Syk kinase regulate COX2 expression.

Animals↗

PubMed2006

Polymorphisms in inflammation-related genes and risk of gastric cancer (Finland).

Helicobacter pylori infection is an important risk factor for gastric cancer, but <3% of carriers of this organism will ever develop gastric cancer. Since inflammation plays a significant role in gastric carcinogenesis, it has been suggested that polymorphisms in genes involved in inflammatory response may partly explain why only a subgroup of patients infected with H. pylori develop gastric cancer. We compared relative frequencies of 17 single nucleotide polymorphisms (SNPs) in eight inflammation-related genes between 112 gastric cancer patients and 208 controls. Cases and controls were selected from a large cohort of Finnish male smokers who were recruited into the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. The studied SNPs were IL-1A (-889 C/T), IL-1B (-511 C/T and -31 T/C), IL-6 (-174 G/C and -597 G/A), IL-8 (-251 T/A, +396 T/G and +781 C/T), IL-8RA (Ex2 +860 G/C), IL-8RB (Exon 3 +1235 T/C, Exon 3 +811 C/T, and Exon 3 +1010 G/A), IL-10 (-819 C/T, -592 C/A, -1082 A/G), and TNF A (-308 G/A, -238 G/A). We found no statistically significant association between any of these SNPs, or the number of pro-inflammatory polymorphisms, with risk of gastric cancer. Our results do not support the hypothesis that polymorphisms in genes involved in the inflammatory response confer differences in gastric cancer risk among different individuals.

Adenocarcinoma↗

PubMed2006

Insulin, glucose, insulin resistance, and incident colorectal cancer in male smokers.

BACKGROUND & AIMS: Hyperinsulinemia is a putative colorectal cancer (CRC) risk factor. Insulin resistance (IR) commonly precedes hyperinsulinemia and can be quantitatively measured by using the homeostasis model assessment-insulin resistance (HOMA-IR) index. To date, few studies have directly examined serum insulin as an indicator of CRC risk, and none have reported associations on the basis of HOMA-IR. METHODS: We performed a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study (n=29,133). Baseline exposure and fasting serum biomarker data were available for 134 incident CRC case and 399 non-case subjects. HOMA-IR was derived as fasting insulin x fasting glucose/22.5. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by using age-adjusted and multivariable-adjusted Cox proportional hazards regression models. RESULTS: Median (interquartile range) values for serum insulin, glucose, and HOMA-IR were 4.1 (2.9-7.2) mIU/L, 101 (94-108) mg/dL, and 0.99 (0.69-1.98) for case subjects and 4.1 (2.7-6.1) mIU/L, 99 (93-107) mg/dL, and 1.02 (0.69-1.53) for non-case subjects, respectively. On the basis of comparison of the highest versus lowest quartiles for each biomarker, insulin (HR, 1.84; 95% CI, 1.03-3.30) and HOMA-IR (HR, 1.85; 95% CI, 1.06-3.24) were significantly associated with incident CRC, whereas glucose was marginally associated with incident CRC (HR, 1.70; 95% CI, 0.92-3.13) in age-adjusted risk models. However, trends across biomarker quartiles were somewhat inconsistent (P trend=.12, .04, and .12, respectively), and multivariable adjustment generally attenuated the observed risk estimates. CONCLUSIONS: Data from this prospective study of male smokers provide limited support for hyperinsulinemia, hyperglycemia, and/or insulin resistance as CRC risk factors.

Aged↗

PubMed2006

Comparison of energy expenditure estimates from 4 physical activity questionnaires with doubly labeled water estimates in postmenopausal women.

BACKGROUND: Physical activity energy expenditure (EE) is an important determinant of health, and epidemiologists have used various methods, such as physical activity and energy intake recalls and records, to estimate energy cost. However, most epidemiologic studies have not validated these methods against the doubly labeled water (DLW) technique for measuring EE. OBJECTIVE: The aim was to compare EE estimated by 4 physical activity questionnaires with that obtained with the DLW technique in free-living postmenopausal women. DESIGN: We measured EE in kcal/d using the DLW method, the Harvard Alumni questionnaire, the Five City Project questionnaire, the Cross-Cultural Activity Participation Study (CAPS) Four Week Activity Recall, and the CAPS Typical Week Activity Survey in 65 healthy postmenopausal women. RESULTS: Compared with DLW, the Harvard Alumni questionnaire, the Five City Project questionnaire, and the CAPS Four Week Activity Recall overestimated (P < 0.05) daily EE by 62%, 16%, and 11%, respectively, whereas the CAPS Typical Week Activity Recall underestimated (P < 0.05) EE by 31%. Both the Harvard Alumni and Five City Project questionnaires overestimated EE in obese and overweight women. CONCLUSIONS: When using 3 of the 4 questionnaire methods, postmenopausal women overestimated EEs. Of all women, obese women overestimated daily EE the most.

Aged↗

PubMed2006

Dietary factors of one-carbon metabolism and prostate cancer risk.

BACKGROUND: Folate is hypothesized to be inversely associated with the risk of several cancers, but such a potential association has not been well studied for prostate cancer. Vitamin B-6, vitamin B-12, methionine, and alcohol can influence folate-related metabolism. OBJECTIVE: The objective was to investigate the associations between dietary factors of one-carbon metabolism and prostate cancer risk within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study. DESIGN: Of the cohort's 27 111 Finnish male smokers aged 50-69 y who had complete dietary data, 1270 had a diagnosis of incident prostate cancer between 1985 and 2002. Folate, vitamin B-6, vitamin B-12, methionine, and alcohol intakes were estimated from a 276-item modified dietary history questionnaire. Cox proportional hazard models, adjusted for age and vitamin supplement use, estimated relative risks (RR) and 95% CIs. RESULTS: Vitamin B-6 intake was inversely associated with prostate cancer risk (RR for highest versus lowest quintile: 0.88; 95% CI: 0.72, 1.07; P for trend = 0.045), whereas vitamin B-12 intake was associated with significantly increased risk (RR = 1.36; 95% CI: 1.14, 1.96; P for trend = 0.01). No association between folate or alcohol intake and prostate cancer risk was observed. No differences were found in the above associations according to stage of disease or subgroups of several potential effect modifiers. CONCLUSIONS: We found no convincing evidence for a protective role of one-carbon metabolism against prostate cancer, although these observations can be generalized only to smokers. The possible modest protective association with vitamin B-6 and the significantly elevated risk with vitamin B-12 intake warrant further investigation.

Aged↗

PubMed2006

Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.

BACKGROUND: A meta-analysis of 19 trials suggested a small increase in the risk of all-cause mortality with high-dose vitamin E supplementation. Little is known, however, about the relation between mortality and circulating concentrations of vitamin E resulting from dietary intake, low-dose supplementation, or both. OBJECTIVE: We examined whether baseline serum alpha-tocopherol concentrations are associated with total and cause-specific mortality. DESIGN: A prospective cohort study of 29 092 Finnish male smokers aged 50-69 y who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study was carried out. Fasting serum alpha-tocopherol was measured at baseline by using HPLC. Only 10% of participants reported vitamin E supplement use at baseline, and thus serum concentrations of vitamin E mainly reflected dietary intake and other host factors. Risks of total and cause-specific mortality were estimated by using proportional hazards models. RESULTS: During up to 19 y of follow-up, 13 380 deaths (including 4518 and 5776 due to cancer and cardiovascular disease, respectively) were identified. Men in the higher quintiles of serum alpha-tocopherol had significantly lower risks of total and cause-specific mortality than did those in the lowest quintile [relative risk (RR) = 0.82 (95% CI: 0.78, 0.86) for total mortality and 0.79 (0.72, 0.86), 0.81 (0.75, 0.88), and 0.70 (0.63, 0.79) for deaths due to cancer, cardiovascular disease, and other causes, respectively; P for trend for all < 0.0001]. Cubic regression spline analysis of continuous serum alpha-tocopherol values indicated greater risk reductions with increasing concentrations up to approximately 13-14 mg/L, after which no further benefit was noted. CONCLUSION: Higher circulating concentrations of alpha-tocopherol within the normal range are associated with significantly lower total and cause-specific mortality in older male smokers.

Aged↗

PubMed2006

Genetic variation in interleukin 8 and its receptor genes and its influence on the risk and prognosis of prostate cancer among Finnish men in a large cancer prevention trial.

The cytokine interleukin 8 (IL-8) may play a role in the pathogenesis of prostate cancer through the modulation of tumour immune response or enhanced angiogenesis. A common polymorphism of the IL-8 (-251) gene, which may affect the production level of the cytokine, has been inversely associated with a number of diseases, including prostate cancer. We examined the most representative single nucleotide polymorphisms (SNPs) for the IL-8 and its receptors (CXCR1 and CXCR2) genes, and conducted a case-control study nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to examine if these SNPs are associated with susceptibility to and prognosis of prostate cancer. Using incidence density sampling, 584 cases of primary prostate cancer and 584 matched controls were selected. In this population, we observed no strong association between the SNPs for IL-8 -251 (A-->T), CXCR1 +860 (C-->G) and CXCR2 -1010 (A-->G) and either the subsequent risk of prostate cancer or individual prognostic factors among cases. Although none of the SNPs studied are likely to have major effects on prostate cancer susceptibility, a role for other polymorphisms associated within these genes cannot be excluded.

Aged↗

PubMed2006

Cellular immune response is not associated with incident cancer or total mortality: a prospective follow-up.

The objective of this study was to determine whether immunologic competence, as measured by lymphocyte stimulation indices from three different ex vivo challenges, is associated with subsequent risk of cancer or total mortality in Linzhou, China, a population at high risk for upper gastrointestinal cancers. Cellular immune function tests were conducted on a subgroup of 381 trial participants after 5.25 years of intervention to evaluate whether nutrient supplementation affected the cellular immune system and found significantly higher T-lymphocyte mitogenic responsiveness to phytohemagglutinin-M among men receiving daily supplementation of beta-carotene (15 mg) plus selenium (50 mug) plus alpha-tocopherol (30 mg) (supplementation factor D) compared with those who did not receive this supplement (P<0.05). The current analysis reports 10 years of post-trial prospective follow-up of these 381 trial participants and identifies 53 incident cancers, 48 (92%) of which were upper gastrointestinal cancers, including 22 esophageal cancers, 22 gastric cardia cancers, and four noncardia gastric cancers. Ninety-one deaths occurred among the 381 participants, including 33 upper gastrointestinal cancer deaths, 23 heart disease deaths, 16 stroke deaths, and seven fatal accidents. Multivariate Cox proportional hazards models including variables for age at time of tests, sex, tobacco smoking, alcohol drinking, and original trial treatment group showed no significant associations between phytohemagglutinin-M, concanavalin-A, or anti-CD3 stimulation indices and subsequent cancer incidence or total mortality. This implies that immune competence, as measured by these stimulation indices, is not associated with incident cancer or total mortality in this population.

Aged↗

PubMed2006

A multiplex tissue immunoblotting assay for proteomic profiling: a pilot study of the normal to tumor transition of esophageal squamous cell carcinoma.

Esophageal cancer remains a highly lethal malignancy for which the genetic and proteomic events are poorly understood. Studies have reported dysregulated proteins in esophageal carcinoma; however, the magnitude of these changes remains largely uncharacterized. Little is known about alterations early in the neoplastic pathway. Using multiplex tissue immunoblotting, we quantified the expression of seven proteins in esophageal carcinogenesis. Regions of normal, dysplasia, and invasive carcinoma of the squamous esophagus in six patients were characterized. Pan-cytokeratin (CK) was essentially unchanged across the transition (0.96 in dysplasia and 0.69 in tumor). Expression levels of annexin 1, CK-4, and CK-14 were all decreased in dysplasia and tumor compared with normal (reference, 1.00): annexin 1, 0.30 in dysplasia and 0.15 in tumor; CK-4, 0.20 in dysplasia and 0.16 in tumor; and CK-14, 0.54 in dysplasia and 0.40 in tumor. Expression of two proteins was increased in dysplasia and tumor versus normal: cyclooxygenase-2, 1.35 in dysplasia and 2.32 in tumor and p53, 1.29 in dysplasia and 2.37 in tumor. Secreted protein, acidic and rich in cysteine, which is expressed in the adjacent stroma, was 1.56-fold higher in stroma underlying dysplasia and 6.20-fold increased in dysplastic stroma surrounding invasive tumor. These findings suggest that changes in protein expression can be detected during the transition to dysplasia and may be useful biomarkers.

Biomarkers, Tumor↗

PubMed2006

Dietary factors of one-carbon metabolism in relation to non-Hodgkin lymphoma and multiple myeloma in a cohort of male smokers.

Reported associations between genetic polymorphisms in folate-metabolizing enzymes and lymphoid malignancies suggest etiologic involvement of one-carbon metabolism and its related dietary exposures. We examined dietary factors of one-carbon metabolism in relation to non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) among 27,111 healthy male smokers who completed baseline dietary questionnaires in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study cohort. During a follow-up of up to 16.4 years (1985-2001), 195 NHL and 32 MM cases were ascertained. Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). There was no significant association between dietary folate and NHL (HR comparing fourth to first quartile, 1.03; 95% CI, 0.68-1.55). Dietary vitamin B12 was inversely associated with NHL (HR, 0.61; 95% CI, 0.37-1.00; P(trend) = 0.06). The inverse association of vitamin B12 was evident for diffuse subtype but did not reach statistical significance. There were no significant associations of dietary vitamin B6 or B2, methionine, or alcohol with NHL. None of the dietary or supplemental one-carbon nutrients were associated with MM, although the power of these analyses was limited. Our results suggest that high intake of vitamin B12 among heavy smokers may be protective against NHL but warrant further studies, including among nonsmokers.

Aged↗

PubMed2006

Selenomethionine treatment does not alter gene expression in normal squamous esophageal mucosa in a high-risk Chinese population.

Selenium is a promising cancer chemoprevention agent. A recent randomized controlled chemoprevention trial found that selenomethionine (SeMet) supplementation for 10 months favorably effected a change in esophageal dysplasia grade among participants who started the trial with mild dysplasia. To further explore the role of SeMet in this trial, we compared gene expression profiles by treatment group using Affymetrix HU 133A chips in before/after supplementation paired normal esophageal biopsies from a subset of 29 trial participants, 16 who received SeMet, and 13 who received placebo. Using P < 0.001 as a cutoff, 11 differentially expressed genes were found in the SeMet supplementation group but these genes did not include either known selenoprotein genes or genes previously shown to be modulated by selenium treatment. Because the number of differentially expressed genes (n = 11) was less than expected by chance (n = 18), we concluded that SeMet supplementation had no measurable effect on gene expression in the normal squamous esophagus of these subjects with dysplasia.

Adult↗

PubMed2006

Lung cancer chemoprevention: a randomized, double-blind trial in Linxian, China.

We examined the effect of supplementation with four different combinations of vitamins and minerals in the prevention of lung cancer mortality among 29,584 healthy adults from Linxian, China. In accord with a partial factorial design, the participants were randomly assigned to take either a vitamin/mineral combination or a placebo for 5.25 years. The combinations tested in this trial were as follows: factor A, retinol and zinc; factor B, riboflavin and niacin; factor C, ascorbic acid and molybdenum; factor D, beta-carotene, alpha-tocopherol, and selenium. Lung cancer deaths (n = 147) identified during the trial period (1986-1991) and 10 years after the trial ended (1991-2001) were the study outcome. No significant differences in lung cancer death rates were found for any of the four combinations of supplements tested in this study, using log-rank tests (all P values are >0.20) or Cox proportional hazards models adjusted for age, sex, commune, and other treatments. No significant interactions were seen for age, sex, or smoking status. Supplementation with combinations of vitamins and minerals at nutrient-repletion levels for 5.25 years did not reduce lung cancer mortality in this nutrient-inadequate population in Linxian, China.

Adult↗