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The importance of the microbial intestinal flora in human cancer and other disease has long been postulated. The effects of some dietary substances, such as prebiotics, on the composition of the flora have been established. The effects of diet on health may be mediated in part by changes in the composition of the intestinal flora. Black tea has been suggested to affect cancer risk, although evidence for this association is equivocal. Polyphenols in black tea could alter the bacterial flora, leading to an increased excretion of carcinogenic fecal bile acids. We analyzed changes in the fecal flora composition and in the fecal bile acid profile in 15 subjects in a black tea feeding study. Fecal samples were collected on d 1, 13 and 20 of the two periods (crossover design) for a total of six samples from each volunteer. We performed fluorescent in situ hybridizations (FISH) and temporal gradient gel electrophoresis (TGGE) to analyze the bacterial flora and determine changes in the bile acid profile enzymatically and by HPLC. Large inter- and intraindividual variation masked any small effects of diet or black tea on the flora composition. However, we did observe a decrease in the amounts of 'other bacteria' detected only by the universal bacterial probe in the FISH analysis. TGGE analyses showed a distinct bacterial profile for each subject that was relatively stable over time. These results indicate that tea drinking affects some flora components, but more sensitive tools and larger studies are required to evaluate effects of diet on the intestinal flora.

Background:Most studies of meat and colorectal adenoma have investigated prevalent events from a single screening, thus limiting our understanding of the role of meat and meat-related exposures in early colorectal carcinogenesis.Methods:Among participants in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who underwent baseline and follow-up sigmoidoscopy (n=17 072), we identified 1008 individuals with incident distal colorectal adenoma. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between meat and meat-related components and incident distal colorectal adenoma using multivariate logistic regression.Results:We observed suggestive positive associations for red meat, processed meat, haeme iron, and nitrate/nitrite with distal colorectal adenoma. Grilled meat (OR=1.56, 95% CI=1.04-2.36), well or very well-done meat (OR=1.59, 95% CI=1.05-2.43), 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) (OR=1.75, 95% CI=1.17-2.64), benzo[a]pyrene (OR=1.53, 95% CI=1.06-2.20), and total mutagenic activity (OR=1.57, 95% CI=1.03-2.40) were positively associated with rectal adenoma. Total iron (diet and supplements) (OR=0.69, 95% CI=0.56-0.86) and iron from supplements (OR=0.65, 95% CI=0.44-0.97) were inversely associated with any distal colorectal adenoma.Conclusion:Our findings indicate that several meat-related components may be most relevant to early neoplasia in the rectum. In contrast, total iron and iron from supplements were inversely associated with any distal colorectal adenoma. [ABSTRACT FROM AUTHOR]

In a cohort of 29,584 residents of Linxian, China, followed from 1985 to 2001, we conducted a case-cohort study of the magnitude of the association of Helicobacter pylori seropositivity with cancer risk in a random sample of 300 oesophageal squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnosed gastric non-cardia adenocarcinomas, and a random sample of the entire cohort (N=1050). Baseline serum was evaluated for IgG antibodies to whole-cell and CagA H. pylori antigens by enzyme-linked immunosorbent assay. Risks of both gastric cardia and non-cardia cancers were increased in individuals exposed to H. pylori (Hazard ratios (HRs) and 95% confidence intervals=1.64; 1.26-2.14, and 1.60; 1.15-2.21, respectively), whereas risk of oesophageal squamous cell cancer was not affected (1.17; 0.88-1.57). For both cardia and non-cardia cancers, HRs were higher in younger individuals. With longer time between serum collection to cancer diagnosis, associations became stronger for cardia cancers but weaker for non-cardia cancers. CagA positivity did not modify these associations. The associations between H. pylori exposure and gastric cardia and non-cardia adenocarcinoma development were equally strong, in contrast to Western countries, perhaps due to the absence of Barrett's oesophagus and oesophageal adenocarcinomas in Linxian, making all cardia tumours of gastric origin, rather than a mixture of gastric and oesophageal malignancies. [ABSTRACT FROM AUTHOR]

Background: From March 1986 through May 1991, we conducted a randomized nutritional intervention trial, the General Population Trial, in Linxian, China, a region with epidemic rates of squamous esophageal and adenomatous gastric cardia cancers. We found that participants who received selenium, beta-carotene, and vitamin E had significantly lower cancer mortality rates than those who did not. In the current study, we examined the relationship between selenium levels measured in pretrial (1985) sera from participants and the subsequent risk of developing squamous esophageal, gastric cardia, and gastric non-cardia cancers during the trial.Methods: This study was designed and analyzed in accord with a stratified case-cohort sampling scheme, with the six strata defined by sex and three age categories. We measured serum selenium levels in 590 case subjects with esophageal cancer, 402 with gastric cardia cancers, and 87 with gastric non-cardia cancers as well as in 1062 control subjects. Relative risks (RRs), absolute risks, and population attributable risk for cancers were estimated on the basis of the Cox proportional hazards models. All statistical tests are two-sided.Results: We found highly significant inverse associations of serum selenium levels with the incidence of esophageal (P: for trend <10(-4)) and gastric cardia (P: for trend <10(-6)) cancers. The RR and 95% confidence interval (CI) for comparison of highest to lowest quartile of serum selenium was 0.56 (95% CI = 0.44-0.71) for esophageal cancer and 0.47 (95% CI = 0.33-0.65) for gastric cardia cancer. The population proportion of these cancers that is attributable to low selenium levels was 26.4% (95% CI = 14.45-38.36). We found no evidence for a gradient of serum selenium associated with incidence of gastric non-cardia cancer (P: for trend =.96), with an RR of 1.07 (95% CI = 0.55-2.08) for the highest to lowest quartile of serum selenium.Conclusions: Our study supports findings from previous prospective studies and randomized trials that variations in selenium levels affect the incidence of certain cancers. In the United States, where intervention trials of selenium are in the planning stages, consideration should be given to including populations at high risk for squamous esophageal and gastric cardia cancers. [ABSTRACT FROM AUTHOR]

Background: Personal history of cancer is an independent risk factor for lung cancer but is omitted from existing lung cancer screening eligibility criteria. In this study, we assess the lung cancer risk among cancer survivors and discuss potential implications for screening., Methods: This was a retrospective, secondary analysis of data from the Surveillance, Epidemiology and End Results (SEER) registry and the MD Anderson Cancer Center (MDACC). We estimated the standardized incidence ratios (SIRs) for lung cancer by site of first primary cancer using data from SEER. We assessed the lung cancer risk among head and neck cancer survivors from MDACC using cumulative incidence and compared the risk ratios (RR) by individuals' screening eligibility status., Results: Other than first primary lung cancer (SIR: 5.10, 95% CI: 5.01-5.18), cancer survivors in SEER with personal history of head and neck cancer (SIR: 3.71, 95% CI: 3.63-3.80) had the highest risk of developing second primary lung cancer, followed by bladder (SIR: 1.86, 95% CI: 1.81-1.90) and esophageal cancers (SIR: 1.78, 95% CI: 1.61-1.96). Head and neck cancer survivors had higher risk to develop lung cancer compared to the National Lung Screening Trial's subjects, (781 vs. 572 per 100,000 person-years, respectively). Head and neck cancer survivors ineligible for lung cancer screening seen at MDACC had significantly higher lung cancer risk than head and neck cancer survivors from SEER (RR: 1.9, p < 0.001)., Conclusion: Personal history of cancer, primarily head and neck cancer, is an independent risk factor for lung cancer and may be considered as an eligibility criterion in future lung cancer screening recommendations., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Telomere length (TL) is a marker of biological aging associated with several health outcomes. High throughput reproducible TL measurements are needed for large epidemiological studies. We compared the novel DNA methylation-based estimator (DNAmTL) with the high-throughput quantitative PCR (qPCR) and the highly accurate flow cytometry with fluorescent in situ hybridization (flow FISH) methods using blood samples from healthy adults. We used Pearson's correlation coefficient, Bland Altman plots and linear regression models for statistical analysis. Shorter DNAmTL was associated with older age, male sex, white race, and cytomegalovirus seropositivity (p<0.01 for all). DNAmTL was moderately correlated with qPCR TL (N=635, r=0.41, p < 0.0001) and flow FISH total lymphocyte TL (N=144, r=0.56, p < 0.0001). The agreements between flow FISH TL and DNAmTL or qPCR were acceptable but with wide limits of agreement. DNAmTL correctly classified >70% of TL categorized above or below the median, but the accuracy dropped with increasing TL categories. The ability of DNAmTL to detect associations with age and other TL-related factors in the absence of strong correlation with measured TL may indicate its capture of aspects of telomere maintenance mechanisms and not necessarily TL. The inaccuracy of DNAmTL prediction should be considered during data interpretation and across-study comparisons.

Several methods have been employed to measure telomere length (TL) in human studies. It has been difficult to directly compare the results from these studies because of differences in the laboratory techniques and output parameters. We compared TL measurements (TLMs) by the three most commonly used methods, quantitative polymerase chain reaction (qPCR), flow cytometry with fluorescence in situ hybridization (flow FISH) and Southern blot, in a cohort of patients with the telomere biology disorder dyskeratosis congenita (DC) and in their unaffected relatives (controls). We observed a strong correlation between the Southern blot average TL and the flow FISH total lymphocyte TL in both the DC patients and their unaffected relatives ( R ² of 0.68 and 0.73, respectively). The correlation between the qPCR average TL and that of the Southern blot method was modest ( R ² of 0.54 in DC patients and of 0.43 in unaffected relatives). Similar results were noted when comparing the qPCR average TL and the flow FISH total lymphocyte TL ( R ² of 0.49 in DC patients and of 0.42 in unaffected relatives). In conclusion, the strengths of the correlations between the three widely used TL assays (qPCR, flow FISH, and Southern blot) were significantly different. Careful consideration is warranted when selecting the method of TL measurement for research and for clinical studies., Competing Interests: The authors declare no conflict of interest.

Background: We investigated the role of antibody responses as potential mechanism for the cross-protective vaccine-efficacies (VE) observed from randomized clinical trials of the HPV16/18 bivalent vaccine. Results HPV31 cases had lower HPV16 antibody levels than controls (OR 4th quartile compared with 1st quartile = 0.63; 95%CI: 0.36-1.08; p-trend = 0.03). HPV31 cases were also less likely to have detectable HPV31 neutralization, and HPV16 avidity than controls. No statistically significant differences by HPV18 antibody or HPV45 neutralization were observed among HPV45 cases and controls. Protection against HPV58 was not associated with any of the markers, confirming the specificity of our findings., Methods: Samples are from three-dose HPV vaccine recipients from the Costa Rica HPV16/18 vaccine trial. Women with a new HPV31, HPV45, or HPV58 infections over four years of follow-up were compared with randomly selected control women--with no new infection with HPV31/45/58--with respect to HPV16 and HPV18 antibody, HPV31, HPV45, and HPV58 neutralization, and HPV16 avidity., Conclusions: High HPV16 levels and avidity, and the ability to neutralize HPV31 were associated with protection against newly detected HPV31 infections, suggesting that the partial VE demonstrated for HPV31 is likely to be mediated at least in part through antibodies induced by HPV16/18 vaccination.

Background: The natural history of human papillomavirus (HPV) infections in older women is critical for preventive strategies, including vaccination and screening intervals, but is poorly understood. In a 7-year population-based cohort study in Guanacaste, Costa Rica, we examined whether women's age and the duration of carcinogenic HPV infections influenced subsequent persistence of infection and risk of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse disease., Methods: At enrollment, of the 9466 participants eligible for pelvic examination, 9175 were screened for cervical neoplasia using multiple methods; those with CIN 2 or worse disease were censored and treated. Participants at low risk of CIN 2 or worse (n = 6029) were rescreened at 5-7 years (passively followed), whereas higher-risk participants (n = 2115) and subsets of low-risk women (n = 540) and initially sexually inactive women (n = 410) were rescreened annually or semiannually (actively followed) for up to 7 years. HPV testing was done using a polymerase chain reaction-based method. We determined, by four age groups (18-25, 26-33, 34-41, and > or =42 years), the proportion of prevalent infections (found at baseline) and newly detected infections (first found during follow-up) that persisted at successive 1-year time points and calculated absolute risks of CIN 2 and CIN grade 3 (CIN 3) or worse during follow-up. P values are two-sided., Results: Regardless of the woman's age, newly detected infections were associated with very low absolute risks of persistence, CIN 2, or worse disease. For newly detected infections, the rate of progression to CIN 2+ (or CIN 3+), after 3 years of follow-up, was not higher for women aged 34 years and older than for younger women. Moreover, rates of newly detected infections declined sharply with age (in the actively followed group, at ages 18-25, 26-33, 34-41, and > or =42 years, rates were 35.9%, 30.6%, 18.1%, and 13.5%, respectively; P < .001). Among prevalent infections, persistent infections among older women (> or =42 years) was higher than that among younger age groups or new infections at any age (P < .01 for comparison of eight groups). Most (66 of 85) CIN 2 or worse detected during follow-up was associated with prevalent infections. Only a small subset (25 of 1128) of prevalent infections persisted throughout follow-up without apparent CIN 2 or worse., Conclusions: The rate of new infections declines with age, and new infections typically do not progress to CIN 2 or worse disease in older women; thus, overall potential benefit of prophylactic vaccination or frequent HPV screening to prevent or detect new carcinogenic HPV infections at older ages is low.

Background: 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) exposure has been demonstrated to cause liver tumors in laboratory rodents. DDT's persistent metabolite and environmental degradation product, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), has also been associated with liver tumors in laboratory animals. Whether DDT and DDE are associated with hepatocarcinogenesis in humans is not clear., Methods: We carried out a nested case-control study among the participants of the Nutritional Intervention Trials in Linxian, China. The case group included 168 individuals who developed liver cancer during the trials, and the control group included 385 individuals frequency-matched on age and sex who were alive and well at the end of the study. Serum concentrations of DDT and DDE were measured by gas chromatography-mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable analysis., Results: In multivariable-adjusted models, the risk of developing liver cancer increased with increased serum DDT concentration (OR for quintile 1 versus quintile 5 = 3.8, 95% CI = 1.7 to 8.6, P(trend) = .0024). In contrast, there was no statistically significant association between liver cancer and serum DDE concentration. The association between high serum DDT concentration and liver cancer was stronger among individuals with DDE concentrations below the median value (odds ratio for tertile 3 versus tertile 1 = 3.55, 95% CI = 1.45 to 8.74) than those with concentrations above the median (OR = 1.70, 95% CI = 0.97 to 2.98). A calculation of crude liver cancer risk found that there would be 26 liver cancers per 100 000 persons per year in the lowest quintile of DDT exposure versus 46 liver cancers per 100 000 persons per year in the highest quintile of DDT exposure., Conclusions: DDT may be a risk factor for liver cancer, particularly among persons with lower DDE concentrations. Risk may be particularly increased among persons exposed directly to DDT (resulting in a higher ratio of DDT to DDE) or, alternatively, risk may be associated with individual ability to metabolize DDT to DDE.

In human immunodeficiency virus type 1 (HIV-1)-infected persons, virus load (serum/plasma level of HIV) predicts outcome. Virus load trends have been characterized in adults and infants but not in children. Virus load trends in 22 male children with hemophilia who acquired HIV-1 postnatally (age 0.7-5.2 years at seroconversion) were studied. The mean HIV-1 load 2 years after seroconversion was 4.40 log10 copies/mL, and the mean change over time (slope) was 0.03 log10 copies/(mL x year). Significant among-children variation was apparent: a random effects model predicted that 95% of children had early virus loads 3.75-5.04 log10 copies/mL and slopes -0.07 to 0.12 log10 copies/(mL x year). Higher early virus loads and higher slopes were each associated with increased mortality (P=.006 and P=.03, respectively). In conclusion, those subjects had virus load trends similar to those in adults. Early virus loads were lower than those in vertically infected infants, which suggests that factors changing soon after birth affect viral replication.