Oh GxE! The Complexity of Body Mass Index and Colon Cancer Risk.
Ontology highlight
ABSTRACT:
SUBMITTER: Ngeow J
PROVIDER: S-EPMC7781441 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Oh GxE! The Complexity of Body Mass Index and Colon Cancer Risk.
Journal of the National Cancer Institute 20210101 1
Similar Datasets
Project description:Genome-wide association studies (GWAS) have identified common variants that predispose individuals to a higher body mass index (BMI), an independent risk factor for endometrial cancer. Composite genotype risk scores (GRS) based on the joint effect of published BMI risk loci were used to explore whether endometrial cancer shares a genetic background with obesity. Genotype and risk factor data were available on 3,376 endometrial cancer case and 3,867 control participants of European ancestry from the Epidemiology of Endometrial Cancer Consortium GWAS. A BMI GRS was calculated by summing the number of BMI risk alleles at 97 independent loci. For exploratory analyses, additional GRSs were based on subsets of risk loci within putative etiologic BMI pathways. The BMI GRS was statistically significantly associated with endometrial cancer risk (P = 0.002). For every 10 BMI risk alleles a woman had a 13% increased endometrial cancer risk (95% CI: 4%, 22%). However, after adjusting for BMI, the BMI GRS was no longer associated with risk (per 10 BMI risk alleles OR = 0.99, 95% CI: 0.91, 1.07; P = 0.78). Heterogeneity by BMI did not reach statistical significance (P = 0.06), and no effect modification was noted by age, GWAS Stage, study design or between studies (P≥0.58). In exploratory analyses, the GRS defined by variants at loci containing monogenic obesity syndrome genes was associated with reduced endometrial cancer risk independent of BMI (per BMI risk allele OR = 0.92, 95% CI: 0.88, 0.96; P = 2.1 x 10-5). Possessing a large number of BMI risk alleles does not increase endometrial cancer risk above that conferred by excess body weight among women of European descent. Thus, the GRS based on all current established BMI loci does not provide added value independent of BMI. Future studies are required to validate the unexpected observed relation between monogenic obesity syndrome genetic variants and endometrial cancer risk.
| S-EPMC4659592 | biostudies-literature
Project description:Obesity is associated with increased colon cancer mortality and lower rates of mammography and Pap testing.We conducted a systematic review to determine whether obesity is associated with lower rates of colon cancer screening. We searched the PubMed, CINAHL, and Cochrane Library databases. Two investigators reviewed citations, abstracts, and articles independently. Two investigators abstracted study information sequentially and evaluated quality independently using standardized forms. We included all studies in our qualitative syntheses. We used random effects meta-analyses to combine those studies providing screening results by the following body mass index (BMI) categories: Normal, 18.5-24.9 kg/m(2) (reference); overweight, 25-29.9 kg/m(2); class I obesity, 30-34.9 kg/m(2); class II obesity, 35-39.9 kg/m(2); and class III obesity, ? 40 kg/m(2).Of 5,543 citations, we included 23 articles. Almost all studies were cross-sectional and ascertained BMI and screening through self-report. BMI was not associated with colon cancer screening overall. The subgroup of obese white women reported lower rates of colon cancer screening compared with those with a normal BMI with combined ORs (95% CI) of 0.87 (0.82-0.93), 0.80 (0.65-0.99), and 0.73 (0.58-0.94) for class I, II, and III obesity, respectively. Results were similar among white men with class II obesity.Overall, BMI was not associated with colon cancer screening. Obese white men and women may be less likely to undergo colon cancer screening compared with those with a normal BMI.Further investigation of this disparity may reduce the risk of obesity-related colon cancer death.
| S-EPMC3930882 | biostudies-literature
Project description:Few studies have examined the association between body mass index (BMI: kg/m(2)) and pancreatic cancer risk in Asian populations. We examined this relationship in 51,251 Chinese men and women aged 45-74 who enrolled between 1993 and 1998 in the population based, prospective Singapore Chinese Health Study. Data were collected through in-person interviews. By December 31, 2011, 194 cohort participants had developed pancreatic cancer. A Cox proportional hazards model was used to estimate hazard ratios (HR) and their 95% confidence intervals (95% CI). We hypothesized the association between BMI and pancreatic cancer risk may vary by smoking status (ever v. never) and there was evidence for this as the interaction between BMI and smoking status was significant (p = 0.018). Among ever smokers, being classified as underweight (BMI <18.5 kg/m(2)), was associated with a significantly elevated risk of pancreatic cancer relative to smokers with a BMI of 21.5-24.4 kg/m(2) (HR = 1.99, 95% CI = 1.03-3.84). This association was strengthened after exclusion of the first three years of follow-up time. Among never smokers, there was no association between BMI and pancreatic cancer risk. However, after excluding pancreatic cancer cases and person-years in the first three years of follow-up, never smokers with a BMI ≥ 27.5 kg/m(2) showed a suggestive increased risk of pancreatic cancer relative to never smokers with a BMI of 21.5-24.4 kg/m(2) (HR = 1.75, 95% CI = 0.93-3.3). In conclusion, Singaporean Chinese who were underweight with a history of smoking had an increased risk of developing pancreatic cancer, whereas there was no significant association between BMI and pancreatic cancer in never smokers.
| S-EPMC3893175 | biostudies-other
Project description:It is unclear how increasing body mass index (BMI) influences risk of cancer in young women. We used data from the Medical Birth, Patient and Cause of Death registers collected between 1982 and 2014 to determine the risk of obesity-related cancer types, breast cancer, all cancer and cancer-related death in relation to BMI in 1,386,725 women, aged between 18 and 45 years, in Sweden. During a median follow-up of 16.3 years (IQR 7.7-23.5), 9808 women developed cancer. The hazard ratio (HR) of endometrial and ovarian cancer increased with higher BMI from 1.08 (95% CI 0.93-1.24) and 1.08 (95% CI 0.96-1.21) among women with BMI 22.5-< 25 to 2.33 (95% CI 1.92-2.83) and 1.48 (95% CI 1.24-1.77), respectively, among women with BMI ≥ 30. There were linear and positive associations between BMI and incident cancer in the ovary, colon, endometrium, pancreas, rectum, gallbladder, esophageal cancer and renal cell carcinoma, as well as death from obesity-related cancer forms. In conclusion, we found that elevated BMI in young women linearly associated with several obesity-related cancer forms, including death from these cancers.
| S-EPMC10940279 | biostudies-literature
Project description:Previously, we found that excess weight already in childhood has positive associations with endometrial cancer; however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial cancer and its sub-types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6-14 years and born 1930-1989 formed the analytical population. BMI was transformed to age-specific z scores. Using linear spline multilevel models, each girl's BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25-7.99, 8.0-10.99, 11.0-14.0 years). Via a link to health registers, 1,020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain in BMI during childhood was positively associated with endometrial cancer but no differences between the different growth periods were detected in models adjusted for baseline BMI. The hazard ratios for the associations with overall growth during childhood per 0.1 z score increase were 1.15 (95% confidence interval [CI]: 1.07-1.24) for all endometrial cancers, 1.12 (95% CI: 1.04-1.21) for estrogen-dependent cancers, 1.16 (95% CI: 1.06-1.26) for endometrioid adenocarcinomas and 1.46 (95% CI: 1.16-1.84) for non-estrogen-dependent cancers. Growth in BMI in early life is positively linked to later endometrial cancer risk. We did not identify any sensitive childhood growth period, which suggests that excess gain in BMI during the entire childhood period should be avoided.
| S-EPMC5132154 | biostudies-literature
Project description:BackgroundExcess weight in adulthood is one of the few modifiable risk factors for pancreatic cancer, and height has associations as well. This leads to question whether body weight and height in childhood are associated with adult pancreatic cancer.ObjectiveTo examine if childhood body mass index (BMI; kg/m2) and height are associated with pancreatic cancer in adult life.MethodsWe linked 293,208 children born from 1930-1982 in the Copenhagen School Health Records Register who had measured values of weights and heights at ages 7-13 years with the Danish Cancer Registry to identify incident pancreatic cancer cases from 1968-2012. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regressions.ResultsDuring 8,207,015 person-years of follow-up, 1,268 pancreatic cancer cases were diagnosed. Childhood BMI z-scores at ages 7-13 years were positively and significantly associated with pancreatic cancer in men and women up to age 70 years; beyond age 70 the associations diminished. The HRs of pancreatic cancer were 1.13 (95% CI: 1.05-1.21) and 1.18 (95% CI: 1.09-1.27) per BMI z-score at ages 7 and 13 years, respectively. A BMI ≥1.5 z-score at ages 7, 10 and 13 years was positively and significantly associated with pancreatic cancer; however, the effect did not differ from having a BMI z-score ≥1.5 at only one of these ages. Positive, albeit non-statistically significant, associations were identified with height.ConclusionsBMI at all ages from 7-13 years is positively and linearly associated with adult pancreatic cancer; the higher the BMI, the higher the risk. Excess childhood BMI may be indicative of processes initiated early in life that lead to this cancer. Prevention of childhood adiposity may decrease the burden of pancreatic cancer in adults.
| S-EPMC5788457 | biostudies-literature
Project description:BackgroundHigh body mass index (BMI) is consistently linked to increased risk of colorectal cancer for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization study to estimate the causal association between BMI and colorectal cancer.MethodsWe used data from 10,226 colorectal cancer cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study-identified variants associated with higher BMI, as an instrumental variable (IV). We compared the IV odds ratio (IV-OR) with the OR obtained using a conventional covariate-adjusted analysis.ResultsIndividuals carrying greater numbers of BMI-increasing alleles had higher colorectal cancer risk [per weighted allele OR, 1.31; 95% confidence interval (CI), 1.10-1.57]. Our IV estimation results support the hypothesis that genetically influenced BMI is directly associated with risk for colorectal cancer (IV-OR per 5 kg/m(2), 1.50; 95% CI, 1.13-2.01). In the sex-specific IV analyses higher BMI was associated with higher risk of colorectal cancer among women (IV-OR per 5 kg/m(2), 1.82; 95% CI, 1.26-2.61). For men, genetically influenced BMI was not associated with colorectal cancer (IV-OR per 5 kg/m(2), 1.18; 95% CI, 0.73-1.92).ConclusionsHigh BMI was associated with increased colorectal cancer risk for women. Whether abdominal obesity, rather than overall obesity, is a more important risk factor for men requires further investigation.ImpactOverall, conventional epidemiologic and Mendelian randomization studies suggest a strong association between obesity and the risk of colorectal cancer.
| S-EPMC4490960 | biostudies-literature
Project description:Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m2 ) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations.
| S-EPMC8019210 | biostudies-literature
Project description:BackgroundBreast cancer survivors are at increased risk for developing second primary cancers compared with the general population. Little is known about whether body mass index (BMI) increases this risk. We examined the association between BMI and second cancers among women with incident invasive breast cancer.MethodsThis retrospective cohort included 6481 patients from Kaiser Permanente Colorado and Washington of whom 822 (12.7%) developed a second cancer (mean follow-up was 88.0 months). BMI at the first cancer was extracted from the medical record. Outcomes included: 1) all second cancers, 2) obesity-related second cancers, 3) any second breast cancer, and 4) estrogen receptor-positive second breast cancers. Multivariable Poisson regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for second cancers associated with BMI adjusted for site, diagnosis year, treatment, demographic, and tumor characteristics.ResultsThe mean age at initial breast cancer diagnosis was 61.2 (SD = 11.8) years. Most cases were overweight (33.4%) or obese (33.8%) and diagnosed at stage I (62.0%). In multivariable models, for every 5 kg/m2 increase in BMI, the risk of any second cancer diagnosis increased by 7% (RR = 1.07, 95% CI = 1.01 to 1.14); 13% (RR = 1.13, 95% CI = 1.05 to 1.21) for obesity-related cancers, 11% (RR = 1.11, 95% CI = 1.02 to 1.21) for a second breast cancer, and 15% (RR = 1.15, 95% CI = 1.04 to 1.27) for a second estrogen receptor-positive breast cancer.ConclusionsWe observed a statistically significant increased risk of second cancers associated with increasing BMI. These findings have important public health implications given the prevalence of overweight and obesity in breast cancer survivors and underscore the need for effective prevention strategies.
| S-EPMC8757319 | biostudies-literature
Project description:While obesity increases colorectal cancer incidence, there are inconsistent results in the prognostic role of obesity or body weight change on survival. This study investigated the prognostic impact of body weight and weight change in stage III or high risk stage II colon cancer patients. We used data from patients enrolled in the phase III AVANT trial. The AVANT trial investigated the efficacy of adding bevacizumab to standard adjuvant chemotherapy (FOFOX or XELOX). Weight change during the first 6 months of adjuvant chemotherapy was measured. Cox proportional hazard model was used to assess the prognostic influence of body weight and weight change. Among 3451 intention-to-treat population, body weight and weight change was measured in 3449 (99.9%) and 2455 (71.1%) patients, respectively. Among 2455 patients, 651 (26.5%) had weight gain over 5 kg and 179 (7.3%) had weight loss over 5 kg. Weight gain was more frequently observed in Asian and male. Neither baseline BMI nor weight change affected recurrence or survival in the Cox proportional hazard model.
| S-EPMC7655869 | biostudies-literature