Smoking, Obesity, Alcohol, and GERD Continue To Be Common, Modifiable Risk Factors for Upper GI Cancers

Smoking, Obesity, Alcohol, and GERD Continue To Be Common, Modifiable Risk Factors for Upper GI Cancers

Prateek Sharma, MD, FASGE, reviewing Wang SM, et al. Am J Gastroenterol 2021 Sep.

Among upper gastrointestinal (UGI) cancers, gastric and esophageal cancers rank third and sixth, respectively, as the most common cause of death due to cancer worldwide. This large, prospective cohort study evaluated patients from the National Institutes of Health-American Association of Retired Persons Diet and Health cohort to determine population-attributable risk (PAR) factors for UGI cancers.

The initial cohort selected in 1995 included 490,605 patients who were followed through 2011 for a diagnosis of UGI cancer. The median follow-up was 15.5 years for a total of 6.6 million person-years of follow-up. UGI cases were identified as esophageal squamous cell carcinoma (ESCC; n=301), esophageal adenocarcinoma (EAC; n=931), gastric cardia cancer (GCA; n=662), and gastric noncardia cancer (GNCA; n=713). This group was compared to a weighted U.S. population from the 2015 National Health Interview Survey for PARs for UGI cancers. 

Higher body mass index was associated with the risk of EAC. The HRs were 1.5 (1.26-1.78) for a BMI of 25 to 29 and 2.22 (1.84-2.68) for a BMI of ≥30. In 2015, obesity was associated with 25.69% of EAC cases, 17.51% of GCA cases, and 7.69% of GNCA cases.

Former and current smokers had an increased risk for both ESCC and EAC. Current smokers had the greatest risk of cancer, with HRs of 5.75 (3.9-8.49) and 3.16 (2.54-3.92) for ESCC and EAC, respectively. The PAR of ever smoking was 57.22% for ESCC, 38.53% for EAC, 41.67% for GCA, and 14.12% for GNCA.

GERD symptoms were associated with EAC (HR, 2.08 [1.61-2.69]) but not with ESCC. The PAR of GERD was 20.57% for EAC and 18.18% for GCA.

Alcohol use increased the risk of ESCC, with HRs of 2.32 (1.67-3.22) for 1 to 3 drinks per day and 6.11 (4.48-8.32) for >3 drinks per day.

Prateek Sharma, MD, FASGE


Smoking continues to be the most significant, modifiable risk factor for all UGI cancers, followed by obesity and GERD for both EAC and GCA. Alcohol consumption of more than 1 drink per day was associated with an increased risk of ESCC. Patients should be actively counseled on these risk factors in an attempt to reduce the incidence of UGI cancers.

Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.


Wang SM, Katki HA, Graubard BI, et al. Population attributable risks of subtypes of esophageal and gastric cancers in the United States. Am J Gastroenterol 2021;116:1844-1852. (

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