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Background: Evidence from observational studies of telomere length (TL) has been conflicting regarding its direction of association with cancer risk. We investigated the causal relevance of TL for lung and head and neck cancers using Mendelian Randomization (MR) and mediation analyses. Methods: We developed a novel genetic instrument for TL in chromosome 5p15.33, using variants identified through deep-sequencing, that were genotyped in 2051 cancer-free subjects. Next, we conducted an MR analysis of lung (16 396 cases, 13 013 controls) and head and neck cancer (4415 cases, 5013 controls) using eight genetic instruments for TL. Lastly, the 5p15.33 instrument and distinct 5p15.33 lung cancer risk loci were evaluated using two-sample mediation analysis, to quantify their direct and indirect, telomere-mediated, effects. Results: The multi-allelic 5p15.33 instrument explained 1.49-2.00% of TL variation in our data (p = 2.6 × 10-9). The MR analysis estimated that a 1000 base-pair increase in TL increases risk of lung cancer [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.20-1.65] and lung adenocarcinoma (OR = 1.92, 95% CI: 1.51-2.22), but not squamous lung carcinoma (OR = 1.04, 95% CI: 0.83-1.29) or head and neck cancers (OR = 0.90, 95% CI: 0.70-1.05). Mediation analysis of the 5p15.33 instrument indicated an absence of direct effects on lung cancer risk (OR = 1.00, 95% CI: 0.95-1.04). Analysis of distinct 5p15.33 susceptibility variants estimated that TL mediates up to 40% of the observed associations with lung cancer risk. Conclusions: Our findings support a causal role for long telomeres in lung cancer aetiology, particularly for adenocarcinoma, and demonstrate that telomere maintenance partially mediates the lung cancer susceptibility conferred by 5p15.33 loci. © 2018 The Author(s) 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

In West Africa, social factors influence whether couples with unmet need for family planning act on birth-spacing desires. Tékponon Jikuagou is testing a social network-based intervention to reduce social barriers by diffusing new ideas. Individuals and groups judged socially influential by their communities provide entrée to networks. A participatory social network mapping methodology was designed to identify these diffusion actors. Analysis of monitoring data, in-depth interviews, and evaluation reports assessed the methodology's acceptability to communities and staff and whether it produced valid, reliable data to identify influential individuals and groups who diffuse new ideas through their networks. Results indicated the methodology's acceptability. Communities were actively and equitably engaged. Staff appreciated its ability to yield timely, actionable information. The mapping methodology also provided valid and reliable information by enabling communities to identify highly connected and influential network actors. Consistent with social network theory, this methodology resulted in the selection of informal groups and individuals in both informal and formal positions. In-depth interview data suggest these actors were diffusing new ideas, further confirming their influence/connectivity. The participatory methodology generated insider knowledge of who has social influence, challenging commonly held assumptions. Collecting and displaying information fostered staff and community learning, laying groundwork for social change.

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10 â'8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci - 9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1∗1301-HLA-DQA1∗0103-HLA-DQB1∗0603 (odds ratio (OR) = 0.59, P = 2.7 × 10-9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers. © 2016 Nature America, Inc. part of Springer Nature, All Rights reserved.

Background: Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but\ud it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility\ud of automatically retrieving information from the medical literature and leveraging this information in GWAS.\ud Methods: We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts,\ud and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the\ud phenotype of interest - the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can\ud subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We\ud initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and\ud subsequently applied it in a two-phase GWAS of oral cancer.\ud Results: Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the\ud oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the\ud ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (perrare-allele\ud log additive p-value [ptrend] = 2.561023\ud ). The combined OR for having one additional rare allele was 0.83 (95% CI:\ud 0.76–0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall\ud UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper\ud aerodigestive tract (UADT), but no additional association signal was found.\ud Conclusion: This study highlights the potential utility of systematically incorporating prior knowledge from the medical\ud literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url: http://services.gate.ac.uk/\ud lld/gwas/service/config).

We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p trend < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p trend = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p trend = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p trend < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97). © 2011 Springer Science+Business Media B.V.

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35). Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case - control studies. Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08-1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95-1.09, P = 0.66; P-heterogeneity (P het) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12-1.34, P = 7 × 10 -6) but not males (OR = 1.02, 95% CI = 0.97-1.08, P = 0.35; P het = 6 × 10-4). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (Phet = 0.86). Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Impact: Further research is warranted to elucidate the mechanisms underlying these observations.©2011 AACR.

Serum samples from 194 cases and 217 controls participating in a case-control study of invasive cervical cancer in Brazil were examined for antibodies to human papillomavirus (HPV) 16 virus-like particles (VLPs) by ELISA. The prevalence of antibody in cases and controls was 47.4 versus 24.4% (P0.001). The prevalence was higher in women who had HPV-16 DNA in the genital tract (54.2%) than in those with other HPVs (36.8%) or no HPVs (44.8%), but the differences were not statistically significant. Among cases and controls, HPV-16 VLP antibodies were associated with a greater number of lifetime sexual partners (chi2 for trend, P0.001). Among controls, age was inversely associated with HPV-16 VLP seroreactivity (chi2 for trend, P = 0.019). The sera were previously tested for antibodies to HPV-16 E6 and E7 oncoproteins; there was no correlation between antibody titers to HPV-16 E6 or E7 and VLPs. The HPV-16 serological assays were compared as screening tests for invasive cervical cancer. The sensitivity and specificity estimates were 47.4 and 75.6% for HPV-16 VLP serology, 63.4 and 89.9% for either HPV-16 E6 or E7 serology, and 53.6 and 93.6% for high titers of either HPV-16 E6 or E7 or VLP antibodies. The utility of HPV-16 VLP ELISA as a screening test for invasive cervical cancer is limited by a high seroprevalence in women with probable prior exposure to HVP 16 but without disease.

Masked sera from 194 cases and 217 controls participating in a case-control study of cervical cancer in Brazil were examined for antibodies to human papillomavirus (HPV) 16 E6 and E7 by radioimmunoprecipitation assay. Radiolabeled full-length E6 and E7 proteins expressed by in vitro transcription and translation in rabbit reticulocyte lysate were used as antigens. The antibody prevalences in cases and controls were: 54.1% versus 6% for E6; 30.4% versus 4.6% for E7; 63.4% versus 10.1% for either E6 or E7; and 21.1% versus 0.5% for both E6 and E7. The corresponding odds ratios were 35 ([95% confidence interval (CI)], 15-83), 10 (95% CI, 4-25), 28 (95% CI, 13-61) and 87 (95% CI, 10-736). The most marked contrast between cases and controls was observed for sera with high antibody titers (cpm6000) with an odds ratio of 239 (95% CI, 29-1946) for E6 or E7. Seroreactivity in cases was partially type specific; women who had HPV-16 DNA in the genital tract had higher antibody prevalence rates than those who were negative for HPV DNA. Reactivity to the E6 protein was associated with the stage of disease; the antibody prevalence was 62.7% in cases with stages II-IV and 31.0% in cases with stage I (P0.005). HPV-16 serology and HPV polymerase chain reaction were compared as markers for invasive cervical cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Head and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases. Methods: We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. Results: Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) =18.5 kg/m2 (2.13, 1.75-2.58) and reduced for BMI >25.0-30.0 kg/m2 (0.52, 0.44-0.60) and BMI =30 kg/m2 (0.43, 0.33-0.57), compared with BMI >18.5-25.0 kg/m2. These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI =18.5 kg/m2 was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m2 was present only in smokers and drinkers. Conclusions: In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies. © The Author 2010; Published by Oxford University Press on behalf of the International Epidemiological Association. All rights reserved.