Dataset Information

Body Size at Different Ages and Risk of 6 Cancers: A Mendelian Randomization and Prospective Cohort Study.

ABSTRACT: It is unclear if body weight in early life affects cancer risk independently of adult body weight. To investigate this question for 6 obesity-related cancers, we performed univariable and multivariable analyses using 1) Mendelian randomization (MR) analysis and 2) longitudinal analyses in prospective cohorts. Both the MR and longitudinal analyses indicated that larger early life body size was associated with higher risk of endometrial (odds ratioMR = 1.61, 95% confidence interval = 1.23 to 2.11) and kidney (odds ratioMR = 1.40, 95% confidence interval = 1.09 to 1.80) cancer. These associations were attenuated after accounting for adult body size in both the MR and cohort analyses. Early life body mass index (BMI) was not consistently associated with the other investigated cancers. The lack of clear independent risk associations suggests that early life BMI influences endometrial and kidney cancer risk mainly through pathways that are common with adult BMI.

SUBMITTER: Mariosa D

PROVIDER: S-EPMC9468294 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Body Size at Different Ages and Risk of 6 Cancers: A Mendelian Randomization and Prospective Cohort Study.

Mariosa Daniela D Smith-Byrne Karl K Richardson Tom G TG Ferrari Pietro P Gunter Marc J MJ Papadimitriou Nikos N Murphy Neil N Christakoudi Sofia S Tsilidis Konstantinos K KK Riboli Elio E Muller David D Purdue Mark P MP Chanock Stephen J SJ Hung Rayjean J RJ Amos Christopher I CI O'Mara Tracy A TA Amiano Pilar P Pasanisi Fabrizio F Rodriguez-Barranco Miguel M Krogh Vittorio V Tjønneland Anne A Halkjær Jytte J Perez-Cornago Aurora A Chirlaque María-Dolores MD Skeie Guri G Rylander Charlotta C Borch Kristin Benjaminsen KB Aune Dagfinn D Heath Alicia K AK Ward Heather A HA Schulze Matthias M Bonet Catalina C Weiderpass Elisabete E Davey Smith George G Brennan Paul P Johansson Mattias M

Journal of the National Cancer Institute 20220901 9

It is unclear if body weight in early life affects cancer risk independently of adult body weight. To investigate this question for 6 obesity-related cancers, we performed univariable and multivariable analyses using 1) Mendelian randomization (MR) analysis and 2) longitudinal analyses in prospective cohorts. Both the MR and longitudinal analyses indicated that larger early life body size was associated with higher risk of endometrial (odds ratioMR = 1.61, 95% confidence interval = 1.23 to 2.11) ...[more]

PMID: 35438160

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Project description:BackgroundObesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain.MethodsWe used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO).FindingsA 1-standard deviation (SD:5.1 kg/m2) increment in BMI levels was found to increase risks of Jass type 1MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.46, 3.13; p-value = 9 × 10-5) and Jass type 2non-MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype CRC (OR: 2.20, 95% CI: 1.26, 3.86; p-value = 0.005). The magnitude of these associations was stronger compared with Jass type 4non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-wildtype CRC (p-differences: 0.03 and 0.04, respectively). A 1-SD (SD:13.4 cm) increment in waist circumference increased risk of Jass type 3non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-mutated (OR 1.73, 95% CI: 1.34, 2.25; p-value = 9 × 10-5) that was stronger compared with Jass type 4 CRC (p-difference: 0.03). A higher body fat percentage (SD:8.5%) increased risk of Jass type 1 CRC (OR: 2.59, 95% CI: 1.49, 4.48; p-value = 0.001), which was greater than Jass type 4 CRC (p-difference: 0.03).InterpretationBody size was more strongly linked to the serrated (Jass types 1 and 2) and alternate (Jass type 3) pathways of colorectal carcinogenesis in comparison to the traditional pathway (Jass type 4).FundingCancer Research UK, National Institute for Health Research, Medical Research Council, National Institutes of Health, National Cancer Institute, American Institute for Cancer Research, Brigham and Women's Hospital, Prevent Cancer Foundation, Victorian Cancer Agency, Swedish Research Council, Swedish Cancer Society, Region Västerbotten, Knut and Alice Wallenberg Foundation, Lion's Cancer Research Foundation, Insamlingsstiftelsen, Umeå University. Full funding details are provided in acknowledgements.

Dataset Information

Body Size at Different Ages and Risk of 6 Cancers: A Mendelian Randomization and Prospective Cohort Study.

Publications

Body Size at Different Ages and Risk of 6 Cancers: A Mendelian Randomization and Prospective Cohort Study.

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