ABSTRACT
Obesity is a major public health concern associated with a higher risk of various comorbidities. Some studies have explored the impact of obesity on cognitive function and, conversely, how lower intelligence might increase the risk of later obesity. The aim of this study is to analyze a complex relationship between body mass index (BMI) and intelligence quotient (IQ), employing a comprehensive approach, including a systematic review, meta-analysis, and Mendelian randomization (MR). We extracted the data from Medline and Embase to identify relevant studies published since June 22, 2009. MR analysis relied on genetic databases such as the Genome-Wide Association Study (GWAS) and the Genetic Investigation of Anthropometric Traits (GIANT) to explore potential causal relationships. The systematic review and meta-analysis encompassed 34 and 17 studies, respectively. They revealed a substantial correlation between obesity and reduced IQ, particularly notable among school-age children (mean difference -5.26; 95% CI: -7.44 to -3.09). Notably, within the IQ subgroup, verbal IQ also exhibited a significant association with a mean difference of -7.73 (95% CI: -14.70 to -0.77) in school-age children. In contrast, the MR did not unveil a significant causal relationship between BMI and IQ, both in childhood and adulthood. This comprehensive analysis underscores a significant correlation between BMI and IQ, particularly in school-age children. However, the MR analysis implies a potentially weaker causal relationship. Future large-scale cohort studies should address potential confounding factors to provide further insights into the BMI-IQ relationship.
ABSTRACT
This study evaluated the influence of genetic polymorphism influencing drug metabolism on survival in taxane- and cisplatin-treated advanced gastric cancer (AGC). Peripheral blood samples from 207 AGC patients treated with first-line chemotherapy of taxane and cisplatin were used. We investigated polymorphisms that influenced the metabolism of taxane (ATP-binding cassette transporter B1 (ABCB1)), cisplatin (glutathione S-transferase M1 (GSTM1), glutathione S-transferase P1 (GSTP1), glutathione S-transferase T1 (GSTT1), excision repair cross complementing 1 (ERCC1), X-ray Cross Complementing group 3 (XRCC3), X-ray Cross Complementing group 4 (XRCC4), X-ray Cross Complementing group 1 (XRCC1), breast cancer (BRCA1)), and 5-fluorouracil (methylene tetrahydrofolate reductase (MTHFR), thymidylate synthase (TYMS)). A total of 207 patients were enrolled between May 2004 and Dec 2008, and 200 patients were analyzed. The overall response rate was 38.5%. Time to progression and overall survival time were 4.3 +/- 0.19 months and 11.9 +/- 1.05 months, respectively. There was no significant association between genetic polymorphism and response rate. However, the BRCA1 mutant TT homozygote was associated with significant prolongation of overall survival (hazard ratio [HR] = 0.43; 95% confidence interval [CI], 0.20-0.92; P = 0.03) and progression-free survival (HR = 0.51; 95% CI, 0.26-1.00; P = 0.05). Also, the XRCC1 194 CT genotype was associated with inferior overall survival, relative to the XRCC1 194 CC homozygotes (HR = 1.49; 95% CI, 0.11-2.07; P = 0.018).These findings suggest that BRCA1 TT and XRCC1 194 CT genotypes could be modest prognostic markers of AGC response in taxane- and cisplatin-treated patients.