Remodeling of sorafenib as an orally bioavailable ferroptosis inducer for Lung Cancer by chemical modification of adenine-binding motif.

Sorafenib (BAY 43-9006) was developed as a multi-kinase inhibitor to treat advanced renal cell, hepatocellular, and thyroid cancers. The cytotoxic effect of sorafenib on cancer cells results from not only inhibiting the MEK/ERK signaling pathway (the on-target effect) but also inducing oxidative damage (the off-target effect). The inhibitory effect of sorafenib on system Xc- (xCT), a cystine/glutamate antiporter, promotes ferroptosis induction and accounts for oxidative damage. While emerging studies on ferroptosis in cancers have garnered increasing attention, the lack of consideration for ferroptosis inducers (FINs) with favorable pharmacokinetics could be problematic. Herein, we remodeled the chemical structure of sorafenib, of which pharmacokinetics and safety are already assured, to customize the off-target effect (i.e., ferroptosis induction) to on-target by disrupting the adenine-binding motif. JB3, a sorafenib derivative (i.e., JB compounds), with a tenfold higher IC50 toward RAF1 because of chemical remodeling, induced strong cytotoxicity in the elastin-sensitive lung cancer cells, while it was markedly reduced by ferrostatin-1. The 24% oral bioavailability of JB3 in rats accounted for a significant anti-tumor effect of orally administrated JB3 in xenograft models. These results indicate that JB3 could be further developed as an orally bioavailable FIN in novel anti-cancer therapeutics.

Enhancing genome editing in hPSCs through dual inhibition of DNA damage response and repair pathways.

Precise genome editing is crucial for establishing isogenic human disease models and ex vivo stem cell therapy from the patient-derived hPSCs. Unlike Cas9-mediated knock-in, cytosine base editor and prime editor achieve the desirable gene correction without inducing DNA double strand breaks. However, hPSCs possess highly active DNA repair pathways and are particularly susceptible to p53-dependent cell death. These unique characteristics impede the efficiency of gene editing in hPSCs. Here, we demonstrate that dual inhibition of p53-mediated cell death and distinct activation of the DNA damage repair system upon DNA damage by cytosine base editor or prime editor additively enhanced editing efficiency in hPSCs. The BE4stem system comprised of p53DD, a dominant negative p53, and three UNG inhibitor, engineered to specifically diminish base excision repair, improves cytosine base editor efficiency in hPSCs. Addition of dominant negative MLH1 to inhibit mismatch repair activity and p53DD in the conventional prime editor system also significantly enhances prime editor efficiency in hPSCs. Thus, combined inhibition of the distinct cellular cascades engaged in hPSCs upon gene editing could significantly enhance precise genome editing in these cells.

Effects of myofibril-palatinose conjugate as a phosphate substitute on meat emulsion quality.

The objective of this study was to investigate a replacement for phosphate in meat products. Protein structural modification was employed in this study, and grafted myofibrillar protein (MP) with palatinose was added to meat emulsion without phosphate. Here, 0.15% of sodium polyphosphate (SPP) was replaced by the same (0.15%) concentration and double (0.3%) the concentration of grafted MP. Although the thermal stability was decreased, the addition of transglutaminase could increase stability. The rheological properties and pH also increased with the addition of grafted MP and transglutaminase. The addition of grafted protein could be perceived by the naked eye by observing a color difference before cooking, but it was not easy to detect after cooking. The cooking loss, emulsion stability, water holding capacity, lipid oxidation, and textural properties improved with the addition of grafted MP. However, the excessive addition of grafted MP and transglutaminase was not recommended to produce a high quality of phosphate replaced meat emulsion, and 0.15% was identified as a suitable addition ratio of grafted MP.

GV1001 Inhibits the Severity of the Ligature-Induced Periodontitis and the Vascular Lipid Deposition Associated with the Periodontitis in Mice.

GV1001, a 16 amino acid peptide derived from the catalytic segment of human telomerase reverse transcriptase, was developed as an anti-cancer vaccine. Subsequently, it was found to exhibit anti-inflammatory and anti-Alzheimer's disease properties. Periodontitis is a risk factor for a variety of systemic diseases, including atherosclerosis, a process in which chronic systemic and vascular inflammation results in the formation of plaques containing lipids, macrophages, foam cells, and tissue debris on the vascular intima. Thus, we investigated the effect of GV1001 on the severity of ligature-induced periodontitis, vascular inflammation, and arterial lipid deposition in mice. GV1001 notably reduced the severity of ligature-induced periodontitis by inhibiting gingival and systemic inflammation, alveolar bone loss, and vascular inflammation in wild-type mice. It also significantly lowered the amount of lipid deposition in the arterial wall in ApoE-deficient mice receiving ligature placement without changing the serum lipid profile. In vitro, we found that GV1001 inhibited the Receptor Activator of NF-κB ligand (RANKL)-induced osteoclast formation and tumor necrosis factor-α (TNF-α)-induced phenotypic changes in endothelial cells. In conclusion, our study suggests that GV1001 prevents the exacerbation of periodontitis and atherosclerosis associated with periodontitis partly by inhibiting local, systemic, and vascular inflammation and phenotypic changes of vascular endothelial cells.

MutSα and MutSß as size-dependent cellular determinants for prime editing in human embryonic stem cells.

Precise genome editing in human pluripotent stem cells (hPSCs) has potential applications in isogenic disease modeling and ex vivo stem cell therapy, necessitating diverse genome editing tools. However, unlike differentiated somatic cells, hPSCs have unique cellular properties that maintain genome integrity, which largely determine the overall efficiency of an editing tool. Considering the high demand for prime editors (PEs), it is imperative to characterize the key molecular determinants of PE outcomes in hPSCs. Through homozygous knockout (KO) of MMR pathway key proteins MSH2, MSH3, and MSH6, we reveal that MutSα and MutSß determine PE efficiency in an editing size-dependent manner. Notably, MSH2 perturbation disrupted both MutSα and MutSß complexes, dramatically escalating PE efficiency from base mispair to 10 bases, up to 50 folds. Similarly, impaired MutSα by MSH6 KO improved editing efficiency from single to three base pairs, while defective MutSß by MSH3 KO heightened efficiency from three to 10 base pairs. Thus, the size-dependent effect of MutSα and MutSß on prime editing implies that MMR is a vital PE efficiency determinant in hPSCs and highlights the distinct roles of MutSα and MutSß in its outcome.

Development of meat spread with omega-3 fatty acids derived from flaxseed oil for the elderly: Physicochemical, textural, and rheological properties.

This study evaluates the characteristics of n-3-enriched meat spread that is in development for consumption by elderly individuals. Herein, flaxseed oil was used as a source of n-3 fatty acid, and macro- and nano-sized flaxseed oil emulsions (FOE) were prepared for the fabrication of meat spreads. As the level of FOE was increased in the meat spreads, significant increases in the levels of omega-3 fatty acids (α-linolenic acid) were observed. Emulsion stability and cooking loss were also improved in meat spreads formulated with FOE compared with those the control. In particular, the addition of FOE generated softer and less chewy meat, owing to its lower melting point and rheological properties. However, the high content of unsaturated fatty acids in the FOE-containing meat spreads increased their susceptibility to lipid oxidation meat. These findings indicate that FOE, particularly macro-sized FOE, has the potential for use in n-3 fatty acid enriched meat products that are intended for consumption by elderly individuals but need to be evaluated for their impacts on shelf-life and sensory quality.

TPX2 Amplification-Driven Aberrant Mitosis in Culture Adapted Human Embryonic Stem Cells with gain of 20q11.21.

BACKGROUND: Despite highly effective machinery for the maintenance of genome integrity in human embryonic stem cells (hESCs), the frequency of genetic aberrations during in-vitro culture has been a serious issue for future clinical applications. METHOD: By passaging hESCs over a broad range of timepoints (up to 6 years), the isogenic hESC lines with different passage numbers with distinct cellular characteristics, were established. RESULT: We found that mitotic aberrations, such as the delay of mitosis, multipolar centrosomes, and chromosome mis-segregation, were increased in parallel with polyploidy compared to early-passaged hESCs (EP-hESCs) with normal copy number. Through high-resolution genome-wide approaches and transcriptome analysis, we found that culture adapted-hESCs with a minimal amplicon in chromosome 20q11.21 highly expressed TPX2, a key protein for governing spindle assembly and cancer malignancy. Consistent with these findings, the inducible expression of TPX2 in EP-hESCs reproduced aberrant mitotic events, such as the delay of mitotic progression, spindle stabilization, misaligned chromosomes, and polyploidy. CONCLUSION: These studies suggest that the increased transcription of TPX2 in culture adapted hESCs could contribute to an increase in aberrant mitosis due to altered spindle dynamics.

TPX2 prompts mitotic survival via the induction of BCL2L1 through YAP1 protein stabilization in human embryonic stem cells.

Genetic alterations have been reported for decades in most human embryonic stem cells (hESCs). Survival advantage, a typical trait acquired during long-term in vitro culture, results from the induction of BCL2L1 upon frequent copy number variation (CNV) at locus 20q11.21 and is one of the strongest candidates associated with genetic alterations that occur via escape from mitotic stress. However, the underlying mechanisms for BCL2L1 induction remain unknown. Furthermore, abnormal mitosis and the survival advantage that frequently occur in late passage are associated with the expression of BCL2L1, which is in locus 20q11.21. In this study, we demonstrated that the expression of TPX2, a gene located in 20q11.21, led to BCL2L1 induction and consequent survival traits under mitotic stress in isogenic pairs of hESCs and human induced pluripotent stem cells (iPSCs) with normal and 20q11.21 CNVs. High Aurora A kinase activity by TPX2 stabilized the YAP1 protein to induce YAP1-dependent BCL2L1 expression. A chemical inhibitor of Aurora A kinase and knockdown of YAP/TAZ significantly abrogated the high tolerance to mitotic stress through BCL2L1 suppression. These results suggest that the collective expression of TPX2 and BCL2L1 from CNV at loci 20q11.21 and a consequent increase in YAP1 signaling promote genome instability during long-term in vitro hESC culture.

The use of interdental cleaning devices and periodontal disease contingent on the number of remaining teeth in Korean adults.

This study aimed to investigate the effect of interdental brushes and dental floss on the prevention of periodontitis in participants with ≥ 20 or < 20 remaining teeth by using the Korea National Health and Nutrition Examination Survey 2016-2018. Data from 11,614 participants were analysed using multivariate logistic regression after adjusting for sociodemographic factors (age and sex), socioeconomic factors (level of education and individual income), oral health-related variables (daily toothbrushing), and systemic health-related variables (smoking, diabetes, and obesity). The adjusted odds ratio (AOR) showed statistically significant results for both floss (AOR, 1.41; 95% confidence interval (CI) 1.22-1.64) and interdental brushes (AOR, 1.16; 95% CI 1.01-1.34). However, no significant difference was found in the subjects with fewer than 20 teeth. The subgroup analysis showed that interdental brushes had a significant preventive effect on women who had more than 20 teeth. Among participants with fewer than 20 teeth, interdental brush users had more periodontitis in men. Regarding those with more than 20 teeth, health inequality was alleviated when floss and interdental brushes were used. The bottom line is that the effect of preventing periodontitis in interdental brushes and dental floss was more evident in participants with ≥ 20 remaining teeth rather than in participants with < 20 remaining teeth.

Pancreas Involvement of Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type, Presenting as Acute Pancreatitis: A Case Report.

BACKGROUND: The main etiology of acute pancreatitis includes biliary origin and alcohol, although various other causes include drugs (i.e., L-asparaginase) or malignant tumors. Since accurate identification of etiologies is crucial for determining therapeutic planning, the assessment of cause should be performed as early as possible. CASE PRESENTATION: A 57-year-old Korean man was admitted for chemotherapy. The patient did not drink alcohol for religious reason. 26 days prior to admission, a 4 cm-sized testicular mass was observed in ultrasound and he received right radial orchiectomy. Extranodal natural killer/T-cell lymphoma, nasal type, was diagnosed. After confirming no additional abnormal findings, chemotherapy (using the regimens Dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) was begun. On Day 8 of chemotherapy, L-asparaginase was started and he complained of sudden onset epigastric pain after 2 days. Acute pancreatitis was diagnosed and, in order to determine if the acute pancreatitis occurred due to L-asparaginase or pancreas involvement of extranodal natural killer/T-cell lymphoma, endoscopic ultrasonography guided fine needle biopsy was performed and observed diffusely infiltrated tumor cells. Therefore, he was given a final diagnosis of acute pancreatitis due to pancreas involvement of extranodal natural killer/T-cell lymphoma, nasal type. DISCUSSION: Acute pancreatitis caused by pancreas involvement of extranodal natural killer/T-cell lymphoma, nasal type, is a very rare disease but can occur during chemotherapy. To identify the cause of acute pancreatitis, endoscopic ultrasonography guided fine needle biopsy can be considered.

Dichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cells.

BACKGROUND: The requirement of the Mek1 inhibitor (iMek1) during naïve pluripotency maintenance results from the activation of the Mek1-Erk1/2 (Mek/Erk) signaling pathway upon leukemia inhibitory factor (LIF) stimulation. METHODS: Through a meta-analysis of previous genome-wide screening for negative regulators of naïve pluripotency, Ptpn11 (encoding the Shp2 protein, which serves both as a tyrosine phosphatase and putative adapter), was predicted as one of the key factors for the negative modulation of naïve pluripotency through LIF-dependent Jak/Stat3 signaling. Using an isogenic pair of naïve and primed mouse embryonic stem cells (mESCs), we demonstrated the differential role of Shp2 in naïve and primed pluripotency. RESULTS: Loss of Shp2 increased naïve pluripotency by promoting Jak/Stat3 signaling and disturbed in vivo differentiation potential. In sharp contrast, Shp2 depletion significantly impeded the self-renewal of ESCs under primed culture conditions, which was concurrent with a reduction in Mek/Erk signaling. Similarly, upon treatment with an allosteric Shp2 inhibitor (iShp2), the cells sustained Stat3 phosphorylation and decoupled Mek/Erk signaling, thus iShp2 can replace the use of iMek1 for maintenance of naïve ESCs. CONCLUSIONS: Taken together, our findings highlight the differential roles of Shp2 in naïve and primed pluripotency and propose the usage of iShp2 instead of iMek1 for the efficient maintenance and establishment of naïve pluripotency.

Cholecalciferol- and α-tocopherol-loaded walnut oil emulsions stabilized by whey protein isolate and soy lecithin for food applications.

BACKGROUND: To overcome the limitations in the use of protein as an emulsifier, soy lecithin, a natural surfactant, was used along with whey protein isolate (WPI) to produce o/w emulsions containing cholecalciferol and α-tocopherol. The physical stability of the emulsions prepared with WPI and varying concentrations of lecithin (0, 1, 2, and 3% w/w) was measured in different heat, pH, and ionic-strength food environmental conditions. RESULTS: All emulsions were shown to be less than 250 nm in size and less than 0.3 in polydispersity index (PDI). The morphology of the emulsions was spherical, and the droplets of the emulsion containing lecithin were thicker and larger than those of the emulsion without lecithin (WPI_L0). After autoclaving, WPI_L0 increased in size from 197.8 ± 1.7 nm to 528.5 ± 28.4 nm, and the retention of cholecalciferol and α-tocopherol decreased to 40.83 ± 0.63% and 49.68 ± 1.84%, respectively. At pH 5.5, near the isoelectric point of WPI, WPI_L0 increased in size due to aggregation, but emulsions containing lecithin remained stable at a PDI under 0.3. Turbiscan stability index of the emulsion prepared with WPI and 3% lecithin was the lowest, indicating good storage stability. In addition, it was confirmed that the higher the lecithin content, the higher the viscosity, and the higher the amount of free fatty acids released in the in vitro digestion model. CONCLUSION: This study can provide theoretical evidence for enhancing the physical stability of protein emulsions by co-stabilization with lecithin, promoting their application in various foods. © 2022 Society of Chemical Industry.

Two case reports of pneumatosis intestinalis in patients with cancer: is surgical management mandatory?

Pneumatosis intestinalis (PI) can be classified into two groups. Primary PI is idiopathic, and patients can recover spontaneously. In contrast, secondary PI is considered fatal due to the high mortality rate associated with mesenteric ischemia. Herein, we describe two patients with PI and concurrent pneumoperitoneum. Both patients were receiving targeted anticancer therapy, yet neither developed abdominal pain nor fatal symptoms. One of the patients underwent surgery, while the other was managed conservatively. Even though there were no complications, the patient who underwent surgery was hospitalized for 34 days, whereas the one who was managed conservatively was hospitalized for only five days. Usually, patients with cancer receiving chemotherapy are immunosuppressed and susceptible to infections. Therefore, based on the patients' clinical features, surgical management of patients with cancer who develop PI after receiving anticancer chemotherapy should be done prudently.

Obstruction of the Hepatic Venous Flow Caused by Intravenous Leiomyomatosis.

Budd-Chiari syndrome (BCS) is a rare intrahepatic vascular disease that is characterized by a hepatic venous outflow obstruction. Intravenous leiomyomatosis (ILs) is a rare complication of a myoma. Here, we report a case of BCS that was caused by intracaval ILs. A woman presented to the emergency department (ED) with abdominal distension that had gradually progressed over a period of 3 years. Bedside ultrasonography and contrast-enhanced computed tomography (CECT) showed a large ascites and pelvic mass. The mass continued to the inferior vena cava and the right atrium. The intracaval mass was obstructing the left and middle hepatic veins. We established a tentative diagnosis of BCS caused by intracaval ILs and attempted surgical resection. Complete resection of the intracaval mass failed because of adhesion; however, she was discharged from the hospital without any postoperative complications. After 3 months, a pelvic ultrasonography showed a recurrence of a 4 × 3 cm pelvic mass. The mass size increased to 6 cm after 30 months. ILs can cause secondary BCS and can lead to life-threatening conditions. Owing to its extreme rarity, early detection in the ED is challenging. Bedside ultrasonography and CECT can enable the early recognition of BCS by ILs.

Luteolin Induces Selective Cell Death of Human Pluripotent Stem Cells.

Despite recent advances in clinical stem cell therapy applications based on human pluripotent stem cells (hPSCs), potential teratoma formation due to the presence of residual undifferentiated hPSCs remains a serious risk factor that challenges widespread clinical application. To overcome this risk, a variety of approaches have been developed to eliminate the remaining undifferentiated hPSCs via selective cell death induction. Our study seeks to identify natural flavonoids that are more potent than quercetin (QC), to selectively induce hPSC death. Upon screening in-house flavonoids, luteolin (LUT) is found to be more potent than QC to eliminate hPSCs in a p53-dependent manner, but not hPSC-derived smooth muscle cells or perivascular progenitor cells. Particularly, treating human embryonic stem cell (hESC)-derived cardiomyocytes with LUT efficiently eliminates the residual hESCs and only results in marginal effects on cardiomyocyte (CM) functions, as determined by calcium influx. Considering the technical limitations of isolating CMs due to a lack of exclusive surface markers at the end of differentiation, LUT treatment is a promising approach to minimize teratoma formation risk.

Systematic identification of a nuclear receptor-enriched predictive signature for erastin-induced ferroptosis.

Erastin, a synthetic lethal compound against cancer expressing an oncogenic RAS, inhibits cystine/glutamate antiporters and causes ferroptosis. However, despite recent evidence for the mechanisms underlying ferroptosis, molecular biomarkers of erastin-dependent ferroptosis have not been identified. Here, we employed isogenic lung cancer cell models to show that a redox imbalance leads to glutathione depletion and ferroptosis. Subsequent transcriptome analysis of pan-cancer cell lines revealed that the activity of transcription factors, including NRF2 and AhR, serve as important markers of erastin resistance. Based on the integrated expression of genes in the nuclear receptor meta-pathway (NRM), we constructed an NRM model and validated its robustness using an independent pharmacogenomics dataset. The NRM model was further evaluated by sensitivity tests on nine cancer cell lines for which erastin sensitivities had not been determined. Our pharmacogenomics approach has the potential to pave the way for the efficient classification of patients for therapeutic intervention using erastin.

ERK Dephosphorylation through MKP1 Deacetylation by SIRT1 Attenuates RAS-Driven Tumorigenesis.

The role of Situin 1 (SIRT1) in tumorigenesis is still controversial due to its wide range of substrates, including both oncoproteins and tumor suppressors. A recent study has demonstrated that SIRT1 interferes in the Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven activation of the Raf-mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway, thereby inhibiting tumorigenesis. However, the molecular mechanism of SIRT1 as a tumor suppressor in RAS-driven tumorigenesis has been less clearly determined. This study presents evidence that the ectopic expression of SIRT1 attenuates RAS- or MEK-driven ERK activation and reduces cellular proliferation and transformation in vitro. The attenuation of ERK activation by SIRT1 results from prompt dephosphorylation of ERK, while MEK activity remains unchanged. We identified that MKP1, a dual specific phosphatase for MAPK, was deacetylated by SIRT1. Deacetylation of MKP1 by direct interaction with SIRT1 increased the binding affinity to ERK which in turn facilitated inactivation of ERK. Taken together, these results suggest that SIRT1 would act as a tumor suppressor by modulating RAS-driven ERK activity through MKP1 deacetylation.

Prospective cohort study of patients with early gastric cancer to detect prodromal Parkinson disease (EGC-PPD): A study protocol and baseline characteristics.

The aim of the current study is to determine the predictive value of alpha-synuclein (AS) aggregation in stomach surgical specimens in combination with selected clinical prodromal markers (CPMs) for development of Parkinson disease (PD) in a normal population. We organized a prospective, long-term, clinicopathologic cohort of patients without neurological diseases who received a radical operation for early gastric cancer (EGC) between ages 50 and 65 years. The participants will be followed for up to 10 years and screened for CPMs and motor symptoms by annual telephone interview. If a participant reports one or more positive answers to screening questions about motor symptoms, they will be regarded as having possible parkinsonism. A movement disorder specialist will then evaluate whether that participant has PD. The primary outcome is the development of PD during the 10-year follow-up. The recruitment period has been completed, and the baseline clinical characteristics are compared between participants with and without possible parkinsonism. A total of 718 participants (mean age: 60.1 ±â€¯5.9) was recruited. The motor symptom screening questionnaire revealed 65 patients with possible parkinsonism (9.0%) at baseline. Patients with possible parkinsonism answered that they had subjective loss of smell more than those without parkinsonism at the time of recruitment (18.5% vs 8.3%) and operation (15.4% vs 6.3%). However, the objective odor discrimination test showed no difference between patients with and without possible parkinsonism. Baseline assessments revealed a sufficient number of patients with possible parkinsonism, which will be confirmed as PD or not in subsequent follow-up visits.

The association between artificial light at night and prostate cancer in Gwangju City and South Jeolla Province of South Korea.

ABSRACT Exposure to artificial light at night (ALAN) has been reported to be associated with various pathological changes including sleep deprivation, circadian rhythm disruption, and melatonin suppression with increase in various cancers such as breast or prostate cancers. In this study, we sought to elucidate the association between ALAN and prostate cancer in 27 districts within Gwangju City and urban and rural areas from South Jeolla Province in South Korea. We analyzed the correlation between ALAN and the incidence of a range of cancers by Poisson regression analysis, after adjustment for confounding risk factors, such as smoking, drinking, obesity, stress, air pollution (particulate matter <10 µm in diameter), urbanization (proportion of urbanized area), and the cancer screening rate. Interestingly, the incidence of prostate cancer was significantly associated with ALAN (risk ratio = 1.02, p = 0.0369) and urbanization (risk ratio = 1.06, p = 0.0055). In particular, comparing the prostate cancer incidence at 25% and 75% level of ALAN, the risk ratio was 1.726 (12.6 over 7.3, respectively). No significant association was observed between ALAN and other cancers, including stomach, esophageal, liver, pancreatic, laryngeal, lung and tracheal, bladder, and brain and central nervous system cancers, as well as lymphoma and multiple myeloma. In conclusion, this study shows that a high incidence of prostate cancer may be independently associated with light pollution and urbanization, which represent significant factors in the rapid process of industrialization of South Korea.

High Incidence of Breast Cancer in Light-Polluted Areas with Spatial Effects in Korea.

We have reported a high prevalence of breast cancer in light-polluted areas in Korea. However, it is necessary to analyze the spatial effects of light polluted areas on breast cancer because light pollution levels are correlated with region proximity to central urbanized areas in studied cities. In this study, we applied a spatial regression method (an intrinsic conditional autoregressive [iCAR] model) to analyze the relationship between the incidence of breast cancer and artificial light at night (ALAN) levels in 25 regions including central city, urbanized, and rural areas. By Poisson regression analysis, there was a significant correlation between ALAN, alcohol consumption rates, and the incidence of breast cancer. We also found significant spatial effects between ALAN and the incidence of breast cancer, with an increase in the deviance information criterion (DIC) from 374.3 to 348.6 and an increase in R2 from 0.574 to 0.667. Therefore, spatial analysis (an iCAR model) is more appropriate for assessing ALAN effects on breast cancer. To our knowledge, this study is the first to show spatial effects of light pollution on breast cancer, despite the limitations of an ecological study. We suggest that a decrease in ALAN could reduce breast cancer more than expected because of spatial effects.