Causal association of childhood obesity with cancer risk in adulthood: A Mendelian randomization study

Abstract

In observational studies of children and adolescents, higher body weight has been associated with distinct disease outcomes, including cancer, in adulthood. Therefore, we performed a two‐sample Mendelian randomization (MR) study to evaluate the causal effect of childhood obesity on long‐term cancer risk. Single‐nucleotide polymorphisms associated with higher childhood body mass index (BMI) from large‐scale genome‐wide association studies were used as genetic instruments. Summary‐level data for 24 site‐specific cancers were obtained from UK Biobank. We found that a 1‐SD increase in childhood BMI (kg/m2) was significantly associated with a 60% increase in risk of pancreatic cancer (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.12‐2.28; P < 0.01) and a 47% increase in risk of esophageal cancer (OR: 1.47; 95% CI: 1.09‐1.97; P < 0.01) in adults. In contrast, there was an inverse association of genetic predisposition to childhood obesity with throat (OR: 0.46; 95% CI: 0.27‐0.79; P < 0.01) and breast cancer (OR: 0.77; 95% CI: 0.64‐0.94; P < 0.01) in adult life. For the other 20 cancers studied, no statistically significant association was observed. Our MR analyses found causal effects of childhood obesity on several cancers. Maintaining a healthy weight should be emphasized during childhood and adolescence to prevent cancer risk later in life.

Obesity and Pancreatic Cancer: Insight into Mechanisms

“…In 2016, more than 1.9 billion adults (39%) were overweight (body mass index (BMI) ≥ 25) with over 650 million (13%) of those being obese (BMI ≥ 30) [1]. Alarmingly, more than 340 million children and adolescents (ages [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] were overweight or obese in 2016 and 39 million children younger than 5 years of age were overweight or obese in 2020 [1]. In the United States of America, the latest data brief from the National Center for Health Statistics reports a prevalence of obesity in adults aged 20 years or older of 42.4% in 2017-2018, which is a considerable increase from 33.7% in 2007-2008 [2].…”

“…Importantly, the association between obesity and risk of PDAC was stronger in men than in women [16]. Besides the importance of early adulthood, growing evidence suggests that adolescent and childhood obesity is also linked to an increased risk of developing PDAC later in life [17][18][19][20]. Here, it is imperative to distinguish the effect of obesity during early cancer development (risk factor for early tumor promotion) from its sometimes-paradoxical effects in the late-stage, advanced disease, where obesity occasionally appears to be associated with improved outcome (obesity paradox) [21][22][23].…”

Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study

“…A Swedish study of more than 200,000 men who had their height and weight measured in adolescence, reported a more than twofold higher risk for later life colorectal cancer for the obese group (BMI ≥30 kg/m 2 ) when compared with the normal weight group (BMI 18.5-<25 kg/m 2 ) (33). A large Israeli study of almost 1.8 million men and women showed that being overweight and obese at adolescence was associated with higher colon cancer risk for both men (HR for overweight, A recent MR study examined the associations between childhood obesity and cancer risk without taking into account adult body size, using a genetic instrument of 15 SNPs from a GWAS of 47,541 children from the Early Growth Genetics (EGG) consortium (35). Effect estimates from this study did not support a positive relationship between childhood BMI and overall colorectal cancer (OR, 1.11; 95% CI, 0.93-1.32) (35).…”

“…A large Israeli study of almost 1.8 million men and women showed that being overweight and obese at adolescence was associated with higher colon cancer risk for both men (HR for overweight, A recent MR study examined the associations between childhood obesity and cancer risk without taking into account adult body size, using a genetic instrument of 15 SNPs from a GWAS of 47,541 children from the Early Growth Genetics (EGG) consortium (35). Effect estimates from this study did not support a positive relationship between childhood BMI and overall colorectal cancer (OR, 1.11; 95% CI, 0.93-1.32) (35). Results from our analyses, that crucially adjusted for adult body size, also reflect little evidence of a positive relationship between early life body size and later life colorectal cancer risk.…”

“…A recent MR study examined the associations between childhood obesity and cancer risk without taking into account adult body size, using a genetic instrument of 15 SNPs from a GWAS of 47,541 children from the Early Growth Genetics (EGG) consortium (35). Effect estimates from this study did not support a positive relationship between childhood BMI and overall colorectal cancer (OR, 1.11; 95% CI, 0.93-1.32) (35). Results from our analyses, that crucially adjusted for adult body size, also reflect little evidence of a positive relationship between early life body size and later life colorectal cancer risk.…”