NDLI: Body mass index and incidence of lung cancer in the HUNT study: using observational and Mendelian randomization approaches

Content Provider	Springer Nature : BioMed Central
Author	Jiang, Lin Sun, Yi-Qian Brumpton, Ben Michael Langhammer, Arnulf Chen, Yue Mai, Xiao-Mei
Abstract	Background Traditional observational studies have shown an inverse association between body mass index (BMI) and lung cancer risk. Mendelian randomization (MR) analysis using genetic variants as instruments for BMI may clarify the nature of the association. Aims We studied the causal association between BMI and lung cancer incidence using observational and MR approaches. Methods We followed up 62,453 cancer-free Norwegian adults from 1995–97 (HUNT2) until 2017. BMI at baseline in HUNT2 was classified as < 25.0, 25.0–29.9 and ≥ 30.0 kg/m2. BMI change over ten years between HUNT1 (1984–86) and HUNT2 was calculated and classified into quartiles. Seventy-five genetic variants were included as instruments for BMI (among which 14 also associated with smoking behavior). Incident lung cancer cases were ascertained from the Cancer Registry of Norway. Cox regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Multivariable MR was used to examine the effect of BMI after genetically controlling for smoking. Results During a median follow-up of 21.1 years, 1009 participants developed lung cancer including 327 with lung adenocarcinoma. The HRs and 95% CIs for incidence of adenocarcinoma were 0.73 (0.58–0.92) for BMI 25.0–29.9 kg/m2 and 0.53 (0.37–0.76) for BMI ≥ 30 kg/m2 compared with BMI < 25.0 kg/m2 in HUNT2 (P for trend < 0.001). However, there was little evidence of a dose–response relationship between the BMI change from HUNT1 to HUNT2 in quartiles and the incidence of adenocarcinoma (P for trend = 0.08). Furthermore, multivariable MR approach suggested a positive association between genetically determined 1 kg/m2 increase in BMI and the incidence of adenocarcinoma (HR 1.25, 95% CI 1.02–1.53). No associations were found with other lung cancer histologic types. Conclusions Our study suggests that the inverse association between baseline BMI and lung adenocarcinoma in observational analysis may not be causal. More MR studies are needed to confirm our finding of a positive association between BMI and lung adenocarcinoma.
Related Links	https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-022-10215-0.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	14712407
DOI	10.1186/s12885-022-10215-0
Journal	BMC Cancer
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2022-11-08
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health Body mass index Lung cancer incidence Multivariable Mendelian randomization Obesity Prospective cohort The HUNT Study Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology Genetics
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.8/2023

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