Jul 2026· Ecotoxicology and Environmental Safety· Vol 321, pp.
120411
· 0 citations· 35 references
Medicine
TL;DR
Findings from both the epidemiological cohort and murine models suggest a significant link between Cd exposure and colorectal neoplasms and reveal the critical roles of inflammation and gut microbiota alterations in Cd-promoted colorectal tumorigenesis.
Abstract
Cadmium (Cd) is a well-established carcinogenic heavy metal linked to the development of various cancers. However, its role in colorectal neoplasms remains unclear. Using a cross-sectional design involving 2332 Chinese participants, we examined the association between Cd exposure and colorectal neoplasms and further explored underlying mechanisms using murine models exposed to environmentally relevant Cd concentrations in drinking water. Epidemiological analysis showed that elevated whole-blood Cd levels were associated with an increased risk of both non-advanced (prevalence ratio [PR] per log2-transformed increment = 1.12, 95% confidence interval [CI]: 1.05-1.20) and advanced colorectal neoplasms (PR per log2-transformed increment = 1.18, 95% CI: 1.01-1.37). In mice, although Cd exposure did not adversely affect overall health status or intestinal structure, it significantly promoted tumorigenesis and malignant progression in the azoxymethane/dextran sulfate sodium (AOM/DSS) model. Notably, Cd exposure did not affect tumor development in the AOM-only model, suggesting that its tumor-promoting effect is dependent on concurrent intestinal inflammation. Indeed, Cd exposure exacerbated DSS-induced colitis in mice. Additionally, Cd exposure induced distinct gut microbiota alterations, characterized by depletion of Lactobacillus intestinalis, as well as members of Turicibacter and Gordonibacter, and enrichment of members of Enterorhabdus, Allobaculum, and Atopobiaceae. Collectively, findings from both the epidemiological cohort and murine models suggest a significant link between Cd exposure and colorectal neoplasms. Moreover, these data reveal the critical roles of inflammation and gut microbiota alterations in Cd-promoted colorectal tumorigenesis.
As of 2025, kidney cancer is the seventh most common cancer according to the National Institutes of Health. Renal cell carcinoma (RCC), the predominant form of kidney cancer, has been linked to environmental exposures, including toxic metals. Cadmium (Cd), a widespread environmental contaminant associated with multiple adverse health effects, enters the body primarily through smoking, diet, or occupational exposure. Elevated blood Cd levels have been observed in RCC patients, and meta-analyses of observational studies have established a positive association between Cd exposure and increased RCC risk. Evidence from previous studies further suggests that Cd may modulate proteins involved in the epithelial-to-mesenchymal transition (EMT), a key process in cancer progression and metastasis. To explore the role of Cd in RCC progression, we examined the effects of subchronic Cd exposure on Renca cells, a murine RCC cell line. Cells were treated with 0.5 µM Cd for one passage (acute exposure) or 10–21 passages (subchronic exposure). We assessed cell proliferation, colony formation, and protein/gene expression via Western blotting and qPCR. Subchronic Cd exposure significantly enhanced proliferation and colony formation in Renca cells compared to controls. It also upregulated estrogen receptor alpha (ER[alpha]) gene expression, consistent with Cd's known metalloestrogenic activity. Conditioned medium from Cd challenged cells stimulated proliferation in untreated control cells, indicating activation of an autocrine growth-promoting pathway. Additionally, acute exposure to Cd reduced E-cadherin expression, a hallmark of EMT induction. These findings demonstrate that subchronic Cd exposure promotes RCC cell proliferation in vitro. Potential underlying mechanisms include elevated ER[alpha] and TGF-[beta] signaling, which may contribute to enhanced metastatic potential via EMT. These results highlight Cd as a relevant environmental modifier of RCC progression and underscore the need for further investigation into its clinical implications for metastasis and disease management via in vivo mouse models currently in development.
Simple Summary People with metabolic and alcohol-associated liver disease may have a higher risk of developing cancer, but it remains unclear how combinations of smoking, physical activity, and diet affect this risk. We studied 25,712 participants from the UKi Biobank to examine whether healthier or less healthy lifestyle patterns were related to new cancer diagnoses. During follow-up, 4416 participants developed cancer. Having more favorable behaviors tended to be associated with a lower cancer risk, whereas having more adverse behaviors tended to be associated with a higher risk, although the pattern was not consistent across every category. Current smoking showed the clearest association with increased cancer risk. Therefore, lifestyle assessment including smoking status may help identify people with metabolic and alcohol-associated liver disease who are at greater cancer risk.
Growing evidence links air pollution to colorectal cancer (CRC) incidence. We examined this association within the large Multiethnic Cohort Study (MEC). Geocoded residential addresses for 98,675 California MEC participants were appended to ambient air pollution measures of PM2.5 (particulate matter [PM] with an aerodynamic diameter <2.5μm), PM10 (PM <10μm), nitrogen dioxide (NO2), nitrogen oxides (NOx), carbon monoxide (CO), and ozone (O3), generated from enrollment (1993-1996) to December 31, 2018. Multivariable-adjusted Cox proportional hazards models evaluated associations of time-varying air pollutants with CRC incidence (n=3,217 cases). We assessed heterogeneity in associations by demographics, tumor stage, and anatomical subsite. CRC incidence increased with PM2.5 exposure (per 10μg/m3; hazard ratio [HR]=1.13, 95% confidence interval [CI]=0.96-1.33), mainly among female (HR=1.29, 95% CI=1.03-1.62) but not among male participants (Pheterogeneity=0.08). CRC incidence also increased with NOx exposure among female (HR=1.22, 95% CI=1.01-1.48) but not male participants (Pheterogeneity=0.07). Increased incidence associated with PM2.5 (HR=1.36, 95% CI=1.05-1.76), NO2 (per 20 parts per billion [ppb]; HR=1.32, 95% CI=1.05-1.68) and CO (per 1000 ppb; HR=1.36, 95% CI=1.01-1.84) exposures were observed for left colon and rectal cancers combined, but not right colon cancers (Pheterogeneity by site=0.08, 0.06 and 0.13, respectively). Associations of PM2.5 and NO2 with rectal cancer incidence differed by population group (Pheterogeneity=0.04 and 0.03, respectively), and was mostly driven by positive associations among Latino participants. In summary, increasing PM2.5, NO2, NOx, and CO exposures were suggestively associated with increased CRC incidence, particularly among female and Latino participants and for left colon and rectal cancers.
U. Ihenacho, Chiu‐Cheng Tseng, Jun Wu et al.· Environmental Research· 0 citations
BACKGROUND
The incidence of thyroid cancer (TC) has risen in recent decades, prompting investigation of environmental contributors beyond traditional risk factors.
SUMMARY
This narrative review examines the association between TC and chemical exposures including per- and polyfluoroalkyl substance (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), phthalates, phenols, nitrates, and polycyclic aromatic hydrocarbons (PAHs). Several studies have shown a link between PFAS and PCB exposure and TC, particularly papillary thyroid cancer. Nitrates, even at currently accepted safe exposure levels have also been shown to have an association with TC. Findings for phthalates, PBDEs, phenols, and PAHs are inconsistent and less studied.
CONCLUSION
Current evidence supports that an association exists between select chemical exposures and TC development, but study limitations prevent any direct link to causation. Further research is needed to guide clinical practice and public health policy.
Rachael Caretti, H. Arain, Herbert Chen· The Oncologist· 0 citations
BACKGROUND
Stomach cancer presents complex etiologic heterogeneity. Ethanol in alcoholic beverages and its metabolite acetaldehyde are carcinogens causally linked to several cancers, but their role in gastric carcinogenesis has not been established. We analyzed harmonized, individual-level prospective data to examine associations between alcohol intake and risk of stomach cancer and its subtypes.
METHODS
2,009,951 participants in 20 cohorts (mean follow-up=9-29 years) within the Pooling Project of Prospective Studies of Diet and Cancer (n = 8,357 incident invasive gastric adenocarcinomas) were included. We used Cox regression to assess associations between alcohol intake and risk of stomach cancer overall and by anatomical and histological subtype and population subgroup, adjusting for confounders.
RESULTS
Evidence for an association between alcohol intake and overall stomach cancer risk was weak (hazard ratio, HR, for ≥30 v 0.1-<5 g/day: 1.06 [95% confidence interval, CI, 0.96 to 1.16], P between-studies heterogeneity=0.43). Positive associations with stomach cancer risk were observed in never smokers (HR, for ≥30 v 0.1-<5 g/day: 1.20 [95% CI, 1.02 to 1.42]; P interaction=0.02) and for Asian studies (HR, 1.21 [95% CI, 1.02 to 1.42]; P interaction=0.01). Modest increased risks were observed for non-cardia cancers such as those of the fundus, body and greater curvature, but not distally located non-cardia cancers. HRs did not differ materially between diffuse- and intestinal-type cancers (P heterogeneity>0.05).
CONCLUSION
There was little evidence of an overall association between alcohol intake and stomach cancer risk, although modest positive associations were observed among never smokers and in Asian cohorts.
H. Jayasekara, Molin Wang, Yang Peng et al.· JNCI Cancer Spectrum· 0 citations
Exposure to toxic metals contributes to the growing burden of noncommunicable diseases (NCDs), yet evidence from sub‐Saharan Africa remains limited. This hospital‐based cross‐sectional study assessed heavy metal (arsenic [As], cadmium [Cd], lead [Pb]) exposure levels and their association with health risks in adult diabetic and hypertensive patients in Cameroon. It involved 178 participants (39 diabetics, 78 hypertensives, 61 comorbid), and the urinary metals were quantified using atomic absorption spectrophotometry and normalized to creatinine. Serum oxidative stress biomarkers including glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and paraoxonase 1 (PON1) were measured. Health risk indices including estimated daily intake (EDI), chronic daily intake (CDI), hazard quotient (HQ), hazard index (HI) and cancer risk (CR), were computed. Proportion contribution trend (PCT), receiver operating characteristic (ROC) and ordinary least squares (OLS) regression were applied for risk and predictive analyses. Diabetic patients exhibited significantly higher (p < 0.05) urinary Cd (5.21 ± 0.83 μg/g creatinine) and Pb (0.66 ± 0.12 μg/g creatinine) levels compared with hypertensive and comorbid patients. GSH levels were markedly lower (p < 0.05) in diabetics than in hypertensives. Although HQs and HIs were < 1, diabetics recorded the highest HI (2.73 × 10−1 ± 2.27 × 10−2; p < 0.05), indicating increased chronic exposure risk. CR values for As and Cd exceeded USEPA thresholds (10−6), with diabetics showing the greatest risk. PCT identified Cd as the dominant contributor to HI across groups. ROC analysis showed that As CDI moderately predicted CR in diabetics (AUC = 0.604; p = 0.047). OLS regression revealed water source and residence as significant determinants of As and Pb exposure. Summarily, diabetic individuals demonstrated disproportionately higher heavy metal exposure and associated carcinogenic risk, largely driven by Cd. Integrating environmental biomonitoring into NCD management is essential to mitigate heavy metal–related health burdens in Cameroon.
Fombat Zenabou Mbebwoh, Muankang Junior Tegha Kum, C. Aphrodite et al.· Journal of Toxicology· 0 citations