The obesity–lung cancer association remains controversial. Concerns over confounding by smoking and reverse causation persist, and the influence of obesity type and effect modifications by race/ethnicity and tumor histology are largely unexplored.
A team of researchers, including Dr. Danxia Yu, assistant professor at Vanderbilt University Medical Center, division of epidemiology, examined associations of BMI, waist circumference (WC), and waist-hip ratio (WHR) with lung cancer risk among 1.6 million Americans, Europeans, and Asians. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95 percent confidence intervals (CIs) with adjustment for potential confounders. Analyses for WC/WHR were further adjusted for BMI. The joint effect of BMI and WC/WHR was also evaluated.
Their findings, published March 6 in the Journal of the National Cancer Institute, identified 23,732 incident lung cancer cases during an average 12-year follow-up. While BMI was generally associated with a decreased risk for lung cancer, WC and WHR were associated with increased risk after controlling for BMI. These associations were seen 10 years before diagnosis in smokers and never smokers, were strongest among blacks, and varied by histological type. Participants with BMIs of less than 25 kg/m2 but high WC had a 40% higher risk of developing lung cancer than those with BMIs of 25 kg/m2 or greater but normal/moderate WC.
The large sample size, long follow-up time, and individual-level data, which included detailed smoking information and tumor histology, enabled the team to address potential confounding and reverse causation and to evaluate associations among never smokers and relatively rare lung cancer types. Moreover, their study included diverse populations from different regions and racial/ethnic groups.
The team found that the obesity–lung cancer associations appeared to differ by race, with blacks being most affected, no matter whether the cutoffs used were from project-wide WHO criteria, cohort-specific quintiles, or race-specific quintiles. The potential variation by race was plausible, given the racial differences in body composition, fat distribution, tobacco carcinogen metabolism, and lung cancer incidence rates.
In the large pooled analysis, the team found a general inverse association of BMI and positive associations of WC and WHR with lung cancer. The obesity–lung cancer association was not completely due to confounding by smoking or reverse causation and may vary by race/ethnicity and tumor histological type. In addition to smoking history and other established risk factors, a “low BMI–high WC/WHR” phenotype could help identify high-risk populations for lung cancer. Their findings also suggest the need for future research to examine the roles of body composition, fat distribution, and obesity-related metabolic disorders in the development of lung cancer.
The authors concluded that the inverse BMI–lung cancer association was not entirely due to smoking and reverse causation. Central obesity, particularly concurrent with low BMI, may help identify high-risk populations for lung cancer.