Leukocyte telomere length not related to risk of esophageal adenocarcinoma

Cancer Med. 2016 Jul 6. doi: 10.1002/cam4.810. [Epub ahead of print]

Leukocyte telomere length in relation to the risk of Barrett’s esophagus and esophageal adenocarcinoma.

Wennerström EC, Risques RA, Prunkard D, Giffen C, Corley DA, Murray LJ, Whiteman DC, Wu AH, Bernstein L, Ye W, Chow WH, Vaughan TL, Liao LM.

Abstract

Christina Wennerström

Chronic inflammation and oxidative damage caused by obesity, cigarette smoking, and chronic gastroesophageal reflux disease (GERD) are major risk factors associated with Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). EAC has been increasing the past few decades, and early discovery and treatment are crucial for survival. Telomere shortening due to cell division and oxidative damage may reflect the impact of chronic inflammation and could possibly be used as predictor for disease development. We examined the prevalence of shorter leukocyte telomere length (LTL) among individuals with GERD, BE, or EAC using a pooled analysis of studies from the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON). Telomere length was measured in leukocyte DNA samples by Q-PCR. Participants included 1173 patients (386 with GERD, 384 with EAC, 403 with BE) and 736 population-based controls. The association of LTL (in tertiles) along the continuum of disease progression from GERD to BE to EAC was calculated using study-specific odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models adjusted for potential confounders. Shorter LTL were less prevalent among GERD patients (OR 0.57; 95% CI: 0.35-0.93), compared to population-based controls. No statistically significant increased prevalence of short/long LTL among individuals with BE or EAC was observed. In contrast to some earlier reports, our findings add to the evidence that leukocyte telomere length is not a biomarker of risk related to the etiology of EAC. The findings do not suggest a relationship between LTL and BE or EAC.

Greater Hip Circumference Inversely Associated with Risk of Barrett’s

Clin Gastroenterol Hepatol. 2016 Jun 2. pii: S1542-3565(16)30267-1. doi: 10.1016/j.cgh.2016.05.032. [Epub ahead of print]

Inverse Association Between Gluteofemoral Obesity and Risk of Barrett’s Esophagus in a Pooled Analysis.

Kendall BJ, Rubenstein JH, Cook MB, Vaughan TL, Anderson LA, Murray LJ, Shaheen NJ, Corley DA, Chandar AK, Li L, Greer KB, Chak A, El-Serag HB, Whiteman DC, Thrift AP

Abstract

BACKGROUND & AIMS: Gluteofemoral obesity (determined by measurement of subcutaneous fat in the hip and thigh regions) could reduce risks of cardiovascular and

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Brad Kendall

diabetic disorders associated with abdominal obesity. We evaluated whether gluteofemoral obesity also reduces the risk of Barrett’s esophagus (BE), a premalignant lesion associated with abdominal obesity.

METHODS: We collected data from non-Hispanic white participants in 8 studies in the Barrett’s and Esophageal Adenocarcinoma Consortium. We compared measures of hip circumference (as a proxy for gluteofemoral obesity) from cases of BE (n = 1559) separately with 2 control groups: 2557 population-based controls and 2064 individuals with gastroesophageal reflux disease (GERD controls). Study-specific odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using individual participant data and multivariable logistic regression and combined using a random-effects meta-analysis.

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RESULTS: We found an inverse relationship between hip circumference and BE (OR per 5-cm increase, 0.88; 95% CI, 0.81-0.96), compared with population-based controls in a multivariable model that included waist circumference. This association was not observed in models that did not include waist circumference. Similar results were observed in analyses stratified by frequency of GERD symptoms. The inverse association with hip circumference was statistically significant only among men (vs population-based controls: OR, 0.85; 95% CI, 0.76-0.96 for men; OR, 0.93; 95% CI, 0.74-1.16 for women). For men, within each category of waist circumference, a larger hip circumference was associated with a decreased risk of BE. Increasing waist circumference was associated with an increased risk of BE in the mutually adjusted population-based and GERD control models.

CONCLUSIONS: Although abdominal obesity is associated with an increased risk of BE, there is an inverse association between gluteofemoral obesity and BE, particularly among men.

12th BEACON Workshop a Success

Thanks to Doug Corley, Jen Schneider, and Kaiser Permanente Northern California for their efforts and contributions in hosting the 12th Annual BEACON Workshop, and to all participants for making it such a fun and worthwhile meeting.

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New PAR and webinar

snip_20160425144841A new PAR  (PAR-16-131: Emerging Questions in Cancer Systems Biology (U01) (http://grants.nih.gov/grants/guide/pa-files/PAR-16-131.html ) has been announced that includes certain population sciences issues. The first round of submissions to the new PAR are due June 24, 2016, and there will be 5 more submission dates through 2018.

A pre-submission webinar will be held this Wed. April 27th from 3-4 pm EST.  For more details see:  https://grants.nih.gov/grants/guide/notice-files/NOT-CA-16-036.html

New BETRNet Funding Opportunity

NCI has approved a new funding opportunity for BETRNet (Barett’s Esophagus Translational Research Network.) While the FOA has not yet been published, the presentation to the Board of Scientific Advisors can be downloaded by clicking here, and the notice of intent to publish is here.

BEACON paper shows shared GERD/Barrett’s genetic background

Lead authors on the following manuscript were Puya Gharahkhani and Stuart McGregor at QIMR Berghofer Medical Research Institute in Brisbane, Australia.

Hum Mol Genet. 2015 Dec 23. pii: ddv512. [Epub ahead of print]

Chronic gastroesophageal reflux disease shares genetic background with esophageal adenocarcinoma and Barrett’s esophagus.

Gharahkhani P, Tung J, Hinds D, Mishra A; Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON), Vaughan TL, Whiteman DC, MacGregor S, BEACON study investigators; Barrett’s and Esophageal Adenocarcinoma Consortium BEACON.

Collaborators (16)

Abstract

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Esophageal adenocarcinoma (EA) is a rapidly fatal cancer with rising incidence in the developed world. Most EAs arise in a metaplastic epithelium, Barrett’s esophagus (BE), which is associated with greatly increased risk of EA. One of the key risk factors for both BE and EA is chronic gastroesophageal reflux disease (GERD). This study used the linkage disequilibrium (LD) score regression and genomic profile risk scoring approaches to investigate the contribution of multiple common single-nucleotide polymorphisms (SNPs) to the risk of GERD, and the extent of genetic overlap between GERD and BE or EA. Using LD score regression, we estimated an overall phenotypic variance of 7% (95% CI 3-11%) for GERD explained by all the genotyped SNPs. A genetic correlation of 77% (s.e. = 24%, P = 0.0012) between GERD and BE and 88% between GERD and EA (s.e. = 25%, P = 0.0004) was estimated using the LD score regression approach. Results from the genomic profile risk scoring approach, as a robustness check, were broadly similar to those from the LD score regression. This study provides the first evidence for a polygenic basis for GERD and supports for a polygenic overlap between GERD and BE, and GERD and EA.

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