Vithayathil M, Carter P, Kar S, et al. - This study’s findings demonstrate that the evidence for body mass index (BMI) as a causal risk factor for cancer is mixed. The study observed that BMI has a consistent causal role in increasing the risk of digestive system cancers and a role for sex-specific cancers with inconsistent directions of effect. In contrast, elevated height seems to have a consistent risk-increasing effect on overall and site-specific cancers.

• Researchers used single nucleotide polymorphisms (SNPs) as instrumental variables for BMI (312 SNPs), FMI (577 SNPs), fat-free mass index (577 SNPs), and height (293 SNPs).

• They calculated relationships of the genetic variants with 22 site-specific cancers and overall cancer in 367,561 individuals from the UK Biobank (UKBB) and with lung, breast, ovarian, uterine, and prostate cancer in large international consortia.

• In the UKBB, it was shown that genetically predicted BMI was positively correlated with overall cancer (odds ratio [OR] per 1 kg/m2 increase 1.01, 95% confidence interval [CI] 1.00–1.02; p = 0.043); several digestive system cancers: stomach (OR 1.13, 95% CI 1.06–1.21; p < 0.001), esophagus (OR 1.10, 95% CI 1.03, 1.17; p = 0.003), liver (OR 1.13, 95% CI 1.03–1.25; p = 0.012), and pancreas (OR 1.06, 95% CI 1.01–1.12; p = 0.016); and lung cancer (OR 1.08, 95% CI 1.04–1.12; p < 0.001).

• Genetically predicted elevated BMI was correlated with an elevated risk of uterine cancer (OR 1.10, 95% CI 1.05–1.15; p < 0.001) and with a lower risk of prostate cancer (OR 0.97, 95% CI 0.94–0.99; p = 0.009) for sex-specific cancers.

• Genetically predicted BMI was positively associated with digestive system cancers (OR 1.04, 95% CI 1.02–1.06; p < 0.001) but not with non-digestive system cancers (OR 1.01, 95% CI 0.99–1.02; p = 0.369) when dividing cancers into digestive system vs non-digestive system.

• The results showed that genetically predicted fat mass index (FMI) was positively correlated with liver, pancreatic, and lung cancer and inversely correlated with melanoma and prostate cancer.

• It has been reported that genetically predicted fat-free mass index was positively correlated with non-Hodgkin lymphoma and melanoma.

• As per the findings, genetically predicted height was correlated with an elevated risk of overall cancer (OR per 1 standard deviation increase 1.09; 95% CI 1.05–1.12; p < 0.001) and multiple site-specific cancers.

• They found similar results in analyses using the weighted median and MR–Egger methods.

• The outcomes validated the positive relationships between BMI and lung and uterine cancer risk as well as the inverse association between BMI and prostate cancer, and, additionally, showed an inverse association between genetically predicted BMI and breast cancer.

• The main limitations are the assumption that genetic associations with cancer outcomes are mediated via the proposed risk factors and that estimates for some lower frequency cancer types are subject to low precision.