Disclosures: The authors report no relevant financial disclosures.
February 22, 2021
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GERD may increase risk for cancers of the larynx, esophagus

Disclosures: The authors report no relevant financial disclosures.
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GERD appeared to increase risk for esophageal adenocarcinoma, esophageal squamous cell carcinoma and laryngeal squamous cell carcinoma, according to results of a study published in Cancer.

Researchers also estimated that approximately 17% of laryngeal and esophageal cancers are associated with GERD, which affects nearly 20% of U.S. adults.

GERD appeared to increase risk for esophageal adenocarcinoma, esophageal squamous cell carcinoma and laryngeal squamous cell carcinoma.

“My group seeks to understand the causes of esophageal cancer. If we understand the risk factors of a type of cancer, we can look for opportunities for prevention to reduce the number of people who develop the cancer,” Christian C. Abnet, PhD, MPH, senior investigator in the division of cancer epidemiology and genetics at NCI, told Healio. “A large body of work demonstrates that GERD is an established risk factor for esophageal adenocarcinoma, the most common type of esophageal cancer in the United States. But across the world, esophageal squamous cell carcinoma is much more common than adenocarcinoma.

“Few studies have investigated GERD as a risk factor for squamous cancers in the upper aerodigestive tract, including the esophagus and the larynx,” he added. “Our findings contribute to developing a complete picture of what may contribute to the development of cancer in these organs.”

Previous studies that evaluated the association between GERD and laryngeal squamous cell carcinoma (LSCC) have had inconsistent results, with most studies limited by size, design or inadequate control for potential cofounders, such as alcohol and tobacco use, researchers noted.

Abnet and colleagues accounted for those factors in examining the association between GERD and risk for LSCC, esophageal adenocarcinoma (EADC) and esophageal squamous cell carcinoma (ESCC) using data from the NIH-AARP Diet and Health Study cohort, established in 1995 and 1996 by mailing questionnaires to 3.5 million AARP members aged 50 to 71 years. The analysis included data of 490,605 (white, 92.55%; men, 59.6%) of the respondents.

Researchers garnered data on GERD diagnosis via Medicare diagnosis codes — which they then multiply imputed five times using logistic regression imputation models to account for the fact GERD data was missing for much of the cohort — and they used state cancer registries to track incident cases of EADC, ESCC and LSCC.

During 6.6 million person-years of follow-up (median follow-up, 15.5 years), researchers observed 876 cases of LSCC, 301 of ESCC and 931 of EADC.

They calculated a multiply imputed prevalence of GERD of 23.7%, with higher incidence observed among women and older individuals.

Results showed a significantly higher risk for EADC among those with GERD (HR = 2.23; 95% CI, 1.72-2.9), a finding that aligned with previous studies, according to the researchers, and persisted in analyses stratified by sex, smoking status and alcohol intake.

Additionally, researchers observed significantly positive associations of GERD and risk for incident LSCC (HR = 1.91; 95% CI, 1.24-2.94) and ESCC (HR = 1.99; 95% CI, 1.39-2.84), which also persisted on stratified analyses.

In a lag analysis that divided follow-up time into four periods (1995-1999, 2000-2004, 2005-2008 and 2009-2011) stratified by sex, smoking status and alcohol intake, researchers found statistically significant higher risk for EADC overall across the 16-year period, with overall higher risks observed for LSCC and ESCC.

Using imputation, researchers estimated 22.04% of people aged 50 to 71 years in the general U.S. population suffered from GERD. Using risk factor distributions from the 2015 National Health Interview Survey (NHIS), researchers calculated that 16.92% (95% CI, 5.36-28.48) of LSCC cases and 17.32% (95% CI, 7.34-27.31) of ESCC cases among that age group were associated with GERD.

“We hypothesized that GERD would be a risk factor for these esophageal squamous cancers,” Abnet said. “We first confirmed that our new exposure method could find the expected association with esophageal adenocarcinoma. We then tested for the associations with squamous cancers of the esophagus and larynx and found that the elevated risk was similar for each of these types of cancer.

“All observational studies have limitations and our study alone does not confirm that GERD raises the risk for all these cancers,” he added. “We expect that our publication may lead other researchers to test this hypothesis in future studies.”

Abnet and colleagues also noted the study may be limited by the use of a medical claim’s definition of GERD and missing data on GERD in both the NIH-AARP Diet and Health Study cohort and NHIS cohort.

“Additional research is needed to replicate these findings and establish GERD as a risk factor for cancers and other diseases,” Abnet said. “Given the modest number of studies that have examined these associations, the most important goal for future research is to generate more data to see if these associations are consistent. Our team is pursuing these questions.”

For more information:

Christian C. Abnet, PhD, MPH, can be reached at National Cancer Institute, National Institutes of Health, MSC 9768, 9609 Medical Center Drive, Rockville, MD, 20850-9768; email: abnetc@mail.nih.gov.