Hyung-Suk Yoon

Ph.D., M.P.H.

Vanderbilt University Medical Center

Research Fellow

PLCO (Learn more about this study)

PLCO-738

Feb 22, 2021

Association of Adulthood Weight Change with Lung Cancer Risk and Mortality

Although obesity is a well-established risk factor for several cancers (e.g., breast cancer), high body mass index (BMI) has been associated with reduced risk and improved lung cancer survival. Evidence from prospective studies has been quite consistent, linking high weight/obesity with lower lung cancer risk and better prognosis. However, the underlying mechanism(s) for this association remains undetermined. It has been suggested that the inverse association might be caused by residual confounding or effect modification by smoking. Cachexia which is observed in patients with lung cancer, is another possible explanation for weight loss and lung cancer mortality. To date, the obesity-lung cancer risk association has been mostly investigated based on a one-time measurement, captured either at the baseline survey for prospective study or at study recruitment for a case-control study. The dynamic change of weight overtime or a long-term effect of obese/underweight could not be adequately considered in this research field. Although very limited, evidence has suggested that adulthood weight change may be involved in lung carcinogenesis and lung cancer prognosis that is different from their role in obesity-related cancers. A recent EPIC study analyzing about 240,000 participants has reported a 6% lower risk of lung cancer per 1 kg/year increment during 8.0 years follow-up after baseline (HR [95% CI] = 0.94 [0.88-0.99]) and a significantly increased risk associated with weight loss of 0.4-5.0 kg per year (HR [95% CI] =1.23 [1.09-1.40]). Another cohort study of Chinese adults (n=84,366) has recently reported that men who gained ≥ 20 kg and reached BMI ≥23 in middle adulthood had a reduced risk of lung cancer (0.58 [0.39-0.87]), and each 5-kg increase in adulthood weight was inversely associated with lung cancer risk (0.86 [0.73-1.01] for men and 0.89 [0.78-1.02] for women). In terms of lung cancer prognosis, one pooled analysis of 16 studies from the International Lung Cancer Consortium, which included 5,454 in non-small cell lung cancer (NSCLC) and 693 small cell lung cancer (SCLC) with weight change information, has reported that a decreased BMI through adulthood was associated with poor survival outcome among patients with NSCLC (HR [95% CI] =1.24 [1.2–1.3]) and SCLC (1.26 [1.0–1.6]) with adjustment for age, sex, smoking status, stage. Furthermore, no studies have fully addressed whether the long-term weight pattern and lung cancer association is modified by race/ethnicity, clinical features of lung cancer (e.g., stage, histological subtypes), smoking status, fat distribution, and other lifestyle factors (e.g., exercise and diet). This proposed study would provide more conclusive results on the association of weight history and lung cancer risk and prognosis and clues for in-depth research on underlying biological mechanisms.