Prevalence and Influencing Factors of Food Allergy in Global Context: A Meta-Analysis.

INTRODUCTION: This study was conducted to evaluate the prevalence and influencing factors of food allergy (FA) in different regions and populations. METHODS: The studies from January 2011 to December 2021 were searched through PubMed, Embase, Cochrane Library, and Web of Science databases. The prevalence of FA was evaluated by calculating the pooled effect estimates and their 95% confidence intervals (CIs). The odds ratio (OR) value was used to investigate the influencing factors of FA. Heterogeneity analysis among studies was performed using I2 analysis. Sensitivity analysis was performed to assess the stability of the results, and Begg's test was used to assess publication bias. RESULTS: A total of 105 published articles, including 3,318,608 participants, were involved in this study. The result indicated that the overall FA prevalence was 4.3% (95% CI: 0.038-0.047). The prevalence of FA was 4.2% in Asia (95% CI: 0.033-0.051), 3.2% in America (95% CI: 0.024-0.041), 4.8% in Europe (95% CI: 0.037-0.060), 1.6% in Africa (95% CI: 0.008-0.026), and 7.5% in Oceania (95% CI: 0.052-0.102). Milk (prevalence: 1.1%, 95% CI: 0.009-0.013) and egg (prevalence: 1.1%, 95% CI: 0.008-0.014) were the most common type of FAs. Male (OR: 1.289, 95% CI: 1.001-1.659), antibiotics exposure during pregnancy (OR: 1.221, 95% CI: 1.162-1.284), breastfeeding (OR: 1.349, 95% CI: 1.011-1.799), asthma (OR: 1.794, 95% CI: 1.443-2.230), eczema (OR: 5.121, 95% CI: 3.575-7.334), family history of atopic disease (OR: 1.893, 95% CI: 1.313-2.730), family history of FAs (OR: 2.096, 95% CI: 1.686-2.594), family history of atopic dermatitis (OR: 1.954, 95% CI: 1.645-2.322), family history of asthma (OR: 1.516, 95% CI: 1.370-1.678), and family history of allergic rhinitis/conjunctivitis (OR: 1.287, 95% CI: 1.191-1.392) increased the risk of FA. CONCLUSION: There were geographical differences in the prevalence of FA. Identification and nursing of FA high-risk populations should be strengthened to improve the quality of life.

Prevalence of food allergy in the Chinese population: A systematic review and meta-analysis of population-based studies.

Background: The prevalence of food allergy is increasing and varies among different populations. Study on the food allergy prevalence is very limited in China. Objective: To assess the prevalence of food allergy in the Chinese population by using systematic evaluation and meta-analysis. Methods: A literature search for population-based epidemiologic study on food allergy in China was conducted in several Chinese and English medical literature data bases. Pooled prevalence data and 95% confidence intervals were calculated to estimate the prevalence of food allergy in China. Subgroup analyses were performed to eliminate and explain the heterogeneity, and also to obtain the prevalence of pooled food allergy in different populations. Results: The overall food allergy prevalence ranged from 4.0% to 8.2%. Subgroup analysis showed a trend of overall increase of food allergy, which varied between 4.4% and 9.9%; The common allergic foods were determined to be mango, shrimp, egg, milk, and crab, with the prevalence of 1.9%, 1.5%, 1.4%, 1.3%, 1.3%, respectively; There is a lack of epidemiologic studies on food allergy in some regions and the overall prevalence of food allergy varied from region to region in China. Conclusion: This study revealed that the prevalence of food allergy in the Chinese population ranged from 4.0% to 8.2%; Food allergy prevalence varied by gender, age, and region. This study highlighted the need for collaborative studies of food allergy with the same rational methods to minimize potential bias caused by methods and techniques. Findings of this study may provide baseline data and scientific reference for improving policies on prevention and control of food allergy.

NCK1 promotes the angiogenesis of cervical squamous carcinoma via Rac1/PAK1/MMP2 signal pathway.

OBJECTIVE: The study was to explore the roles of Nck1 in the angiogenesis of cervical squamous cell carcinoma (CSCC). METHODS: mRNA and protein levels were evaluated with real-time quantitative PCR and immunohistochemisty/western blotting respectively. The cancer microvessel density (MVD) was assayed with CD34 endothelial labeling. Nck1 gene knock-in (SiHa-Nck1+) and knock-down (SiHa-Nck1-) were achieved by gene transfection and siRNA respectively. Protein level from cellular supernatant was measured with ELISA. Proliferation, migration and tube formation of the Human Umbilical Vein Endothelial cells (HUVECs) were evaluated by CCK-8 cell viability assay, transwell chamber assay and in vitro Matrigel tubulation assay respectively. RESULTS: Nck1 level gradually increased from normal cervical epithelia to high-grade CIN, overexpressed in CSCC and was associated with cancer MVD. The ability of proliferation, migration and tube formation of HUVECs was enhanced in SiHa-Nck1+-treated while decreased in SiHa-NcK1--treated cells compared to SiHa-control-treated cells. Mechanistically, RAC1-GTP, p-PAK1 and MMP2 were increased in SiHa-NCK1+ cells and pretreatment with the Rac1 inhibitor (NSC23766) significantly decreased their levels. Furthermore, inhibition of PAK1 reduced MMP2 level in SiHa-Nck1+ cells whereas the level of Rac1-GTP was unaltered. Also, inhibition of Rac1 or PAK1 impaired angiogenesis-inducing capacity of cancer cells. CONCLUSIONS: Nck1 promotes the angiogenesis-inducing capacity of CSCC via the Rac1/PAK1/MMP2 signal pathway.

Astrocyte elevated gene-1 promotes progression of cervical squamous cell carcinoma by inducing epithelial-mesenchymal transition via Wnt signaling.

OBJECTIVE: The aim of this study was to investigate the association of astrocyte elevated gene-1 (AEG-1) with epithelial-mesenchymal transition of cervical squamous cell carcinoma (CSCC) and the underlying mechanisms. METHODS: The expression of proteins was determined by immunohistochemistry in tissues. Overexpression and knockdown of AEG-1 in SiHa cells were achieved by stable AEG-1 gene transfection (SiHa-AEG-1+) and AEG-1-siRNA (SiHa-AEG-1-), respectively. The cellular levels of messenger RNA and proteins were assessed with reverse transcription polymerase chain reaction and Western blotting, respectively. The cell invasion capacity was assessed by the chamber invasion assay. RESULTS: AEG-1 was overexpressed in clinical CSCC and associated with lymph node metastasis, parametrial involvement, stromal invasion, and vascular invasion. A high level of vimentin and a low level of E-cadherin were also detected in the cancer tissues. AEG-1 expression was positively correlated with vimentin expression and negatively with E-cadherin expression in CSCC tissues. In addition, high level of AEG-1 was related to unfavorable prognosis of CSCC. On a cellular level, overexpression of AEG-1 was found to lead to an up-regulation of vimentin and a down-regulation of E-cadherin on messenger RNA and protein level in SiHa cells, whereas AEG-1 knockdown led to a contrary result. Meanwhile, the nuclear levels of NF-κB p65 and ß-catenin were also increased in SiHa-AEG-1+, whereas their nuclear levels were decreased in SiHa-AEG-1-. Inhibition of Wnt signaling significantly reduced vimentin level and enhanced E-cadherin level in SiHa-AEG+, but inhibition of NF-κB signaling did not. SiHa-AEG-1+ and SiHa-AEG- showed an enhanced and a decreased invasive capacity, respectively. The enhanced invasiveness of SiHa-AEG-1+ was weakened by inhibition of Wnt signaling. CONCLUSIONS: AEG-1 was associated with the progression of CSCC by promoting epithelial-mesenchymal transition via Wnt signaling pathway.

CRIP1 supports the growth and migration of AML-M5 subtype cells by activating Wnt/ß-catenin pathway.

Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous hematopoietic disorder. To effectively eradicate AML, it is urgent to develop new therapeutic approaches and identify novel molecular targets. In silico analysis indicated that the expression of cysteine-rich intestinal protein 1 (CRIP1) was significantly elevated in AML cells and correlated with worse overall survival of the AML patients. However, its specific roles in AML remain elusive. Here we demonstrated that CRIP1 acted as a key oncogene to support AML cell survival and migration. Using a loss-of-function analysis, we found that CRIP1 silencing in U937 and THP1 cells by lentivirus-mediated shRNAs resulted in a decrease in cell growth, migration and colony formation, and an increase in chemosensitivity to Ara-C. CRIP1 silencing induced cell apoptosis and G1/S transition arrest. Mechanically, CRIP1 silencing caused inactivation of Wnt/ß-catenin pathway through upregulating axin1 protein. The Wnt/ß-catenin agonist SKL2001 markedly rescued the cell growth and migration defect induced by CRIP1 silencing. Our findings reveals that CRIP1 may contribute to AML-M5 pathogenesis and represent a novel target for AML-M5 treatment.

Prevalence of self-reported food allergy among adults in Jiangxi, China.

Background: Food allergy has become an increasingly important public health problem. However, information regarding epidemiological studies of food allergy among Chinese adults is very limited. This study aims to estimate the prevalence of self-reported food allergy among adults in China. Method: A population-based cross-sectional study was administered to estimate the prevalence of self-reported food allergy on the basis of a face-to-face questionnaire survey. The participants were recruited by cluster random sampling from three prefectures in Jiangxi Province, China. Results: A total of 12 082 questionnaires were distributed, and 11 935 (98.8%) of completed ones were collected. The prevalence of self-reported food allergy was 4.0% (3.1% in men and 4.8% in women), self-reported doctor-diagnosed food allergy accounted for 1.4%. The most common allergic symptom was skin reaction showing in 63.9% of the participants with self-reported food allergy. The main allergic foods were shrimp, mollusks, and mango, accounting for the prevalence of 39.8%, 20.8%, and 18.7%, respectively. The self-reported food allergy was significantly linked with gender, age group, body height and other allergic conditions. Conclusions: The prevalence of self-reported food allergy is about 4.0% among adults in China. The three most common allergenic foods were shrimp, mollusks and mango. Gender, age, and other allergic diseases could be contributing factors associated with food allergy in adults. These findings will provide scientific basis for the further research and prevention of food allergy in adults.

MALAT1 Induces Food Allergy by Promoting Release of IL-6 from Dendritic Cells and Suppressing the Immunomodulatory Function of Tregs.

Background: Dendritic cells (DCs) comprise a valuable target for immune-modulation in food allergy (FA). Long noncoding RNA (lncRNA), metastasis associated lung adenocarcinoma transcript 1 (MALAT1) has immunomodulatory capacities and may influence the outcome of DC antigen presentation. However, the precise molecular mechanisms underlying the implication of MALAT1 in FA remain unclear. Methods: BALB/c mice were sensitized to ovalbumin in accordance with a model of FA protocol and injected with adenovirus. After modeling, immunohistochemistry was performed to analyze the jejunal tissues of FA mice and hematoxylin-eosin staining and toluidine blue staining were performed to detect inflammation and mast cell numbers. Ovalbumin-sensitized mice were monitored for symptoms of diarrhea and rectal temperature. Immature DCs were stimulated by oxidized low density lipoprotein to trigger their maturation. Results: MALAT1 was found highly expressed in mice with FA, and its silencing relieved allergic reactions with reduction in intestinal inflammatory cells and mast cells in FA mice. MALAT1 aggravated symptoms by downregulating zinc finger protein 36 (ZFP36). MALAT1 also downregulated ZFP36 expression to promote interleukin-6 (IL-6) secretion by DCs and maturation of DCs, with increased serum-specific immunoglobulin E (IgE) and IgG1 levels. Conclusion: Together, these data suggested that therapeutically blocking MALAT1 in FA could reduce the severity of FA by decreasing secretion of IL-6 by DCs and suppressing the immunomodulation of Tregs.

Epidemiological survey of self-reported food allergy among university students in China.

The aim of this study was to investigate the prevalence of self-reported food allergy among university students in China. A cluster-random sampling population-based cross-sectional study using self - administrated questionnaire was conducted with 2538 college students recruited from 6 universities in China. The questionnaire included data on age, sex, weight, height, FA, comorbid allergic diseases, family history, and understanding food allergy. Data were analyzed by SPSS 25.0 statistical software. Multivariate logistic regression analysis was performed to analyze the risk factors related to self-reported food allergy and estimate the odds ratio. A total of 2538 questionnaires were distributed to the undergraduate students and 2313 completely effective questionnaires were collected, the effective response rate was 91.1%. 834 males and 1479 females were recruited, and their age ranged from 18 to 25 years old. The prevalence of self-reported food allergy was 15.7%, and the rate of doctor-diagnosed food allergy was 8.4%. The leading food allergens included shrimp, shellfish, milk, egg, peach, mango, beef, and peanut, and the prevalence of shrimp allergy was the highest (5.8%). The main clinical manifestation included skin mucous membrane and respiratory symptoms. The prevalence of food allergy were statistically significant difference (P < .05) between different age groups, family history, sun exposure times, smoking, and antibiotic use. Over 45% college students know little about food allergy. The prevalence of self-reported food allergy among Chinese college students was high (15.7%). Shrimp was the main allergenic food, followed by shellfish, milk, egg, peach, and mango. Family history, sun exposure, obesity, and using antibiotics may be the influencing factors of food allergy. The Chinese undergraduates lacked the knowledge about food allergy. Thus, it is necessary to strengthen the health education program on food allergy for college students in China and other middle high-income nations.

Prevalence of parent-reported food allergy among children in China: A population-based cross-sectional survey.

Objective: The prevalence of food allergy (FA) has been increasing in recent years and has become an important public health, food safety, and clinical nutrition problem. However, population-based studies on the prevalence of FA are very limited in China. This study aims to determine the prevalence and pattern of parent-reported FA among school children in Jiangxi Province, China. Methods: A multicenter cross-sectional study on FA was conducted on primary school children aged 6-11 years old using random cluster sampling with a questionnaire survey. Parent-reported FA was used and defined as individual-reported FA by parent or guardian through a questionnaire in this study. Result: Among the total of 8,856 (96.36%) complete questionnaires received, 727 (8.2%) children had adverse reactions to food (ARF). The prevalence rates of parent-reported FA and doctor-diagnosed FA were 6.2% and 3.3%, respectively. Animal-derived foods were the main causative source of FA, and the three leading allergenic foods were shrimp, mango, and mollusks. Skin reactions were the most common clinical manifestations of FA, accounting for 63.7%, and 45.32% of the subjects with parent-reported FA experienced severe allergic reactions. There was a significant difference in parent-reported FA between different survey centers, and FA risk increased significantly in children with other allergic diseases (P<0.001) and small family size (P=0.026). The FA prevalence was significantly higher among children aged 8-11 years than those aged 6-7 years (P=0.020). Conclusions: A high prevalence of parent-reported FA was observed among children in general primary schools in Jiangxi Province, China. Shrimp, mango, and mollusks were the most common causative foods. The main common symptoms of FA were adverse reactions relating to the skin system. The rate of severe allergic reactions was also high in Jiangxi Children with reported FA. Local standards and policies for the prevention and management of FA need to be adjusted on a timely basis according to actual local conditions.

Prevalence and factors for food allergy in different populations from different regions: A protocol for a systematic review and meta-analysis.

BACKGROUND: To determine the prevalence of food allergy (FA) and factors associated with these occurrences in different populations from different regions. MATERIALS AND METHODS: The literature search will be conducted via Pubmed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Vip and Wanfang databases. Ratio rate (RR), odds ratio (OR) and 95% confidence intervals (CIs) will be adopted to evaluate prevalence and factors for FA in different populations from different regions. When the heterogeneity is small (I2<50%), the fixed effect model will be analyzed, otherwise, random effects model analysis will be performed. When the heterogeneity is large (I2≥50%), Meta regression will be used to explore the sources of inter-study heterogeneity. When the heterogeneity is large (I2≥50%) and the results are statistically significant (P<0.05), subgroup analysis will be analyzed based on age, gender, race/region, literature quality and other factors. Funnel plots will be used to reflect reporting bias and the Begg's test will be used to test the symmetry of the funnel plots. When publication bias occurs, "cut-and-fill" method will be adopted to adjust publication bias. And sensitivity analysis will be performed for all outcome indicators. DISCUSSION: This meta-analysis will evaluate the prevalence of FA and factors associated with these occurrences in different populations from different regions on the basis of existing evidences. Our study may be crucial to analyze similarities and differences regarding FA between different individuals from diverse regions and eventually define preventive or diagnostic approaches specifically tailored to certain populations and regions. SYSTEMATIC REVIEW REGISTRATION: OSF registration number: 10.17605/OSF.IO/VQXU9.

Lipoxin A4 promotes autophagy and inhibits overactivation of macrophage inflammasome activity induced by Pg LPS.

OBJECTIVE: To explore the role of lipoxin A4 (LXA4) on inflammasome and inflammatory activity in macrophages activated by Porphyromonas gingivalis lipopolysaccharide (PgLPS) one of the major causative agents of chronic periodontitis. METHODS: The mouse macrophage cell line RAW264.7 was used to produce an activated inflammation model. Markers of inflammasome and inflammatory activity and autophagy were assessed by ELISA, reverse transcription polymerase chain reaction (RT-PCR), and Western blot assay. RESULTS: Markers of inflammasome activity, inflammation and autophagy increased with Pg LPS concentration. They also increased with increasing exposure to Pg LPS up to 12h but decreased at 24h. However, markers of autophagy increased. Phosphorylated NF-κBp65 decreased with LXA4, which was similar to results obtained with the autophagy inducer, rapamycin. CONCLUSIONS: LXA4 promoted autophagy and inhibited activation of inflammasomes and inflammation markers in macrophage inflammation induced by PgLPS and this action was linked to the phosphorylation of NF-κB.

Short-Interval Sequential CAR-T Cell Infusion May Enhance Prior CAR-T Cell Expansion to Augment Anti-Lymphoma Response in B-NHL.

Chimeric antigen receptor (CAR)-T cell therapy emerges as a new treatment for refractory or relapsed (r/r) B-cell non-Hodgkin lymphoma (B-NHL); however, the overall response rate (ORR) of which in the B-NHL patients is much lower compared to the patients with r/r B acute lymphoblastic leukemia (B-ALL). We previously confirmed that sequential infusions of CD20 and CD22 CAR-T cells significantly improved the prognosis of the B-NHL patients, while some advanced patients still progressed to death during these CAR-T cell treatments. In this study, we showed that timely sequential administration of the second CAR-T cells could enhance expansion of prior CAR-T cells with stronger tumor-killing capacity in vitro and in vivo. We further conducted compassionate treatments on two advanced B-NHL patients with short-interval sequential infusions of CD19/22/20 CAR-T cells. Disease progression was observed in both patients after primary CAR-T cell infusion but robust re-expansion of prior CAR-T cells and anti-tumor effects was induced by infusion of a secondary CAR-T cells. These results indicate sequential infusions of CAR-T cells with a short interval may improve therapeutic efficacy in the B-NHL patients by promoting expansion of prior CAR-T cells.

Corrigendum: Short-Interval Sequential CAR-T Cell Infusion May Enhance Prior CAR-T Cell Expansion to Augment Anti-Lymphoma Response in B-NHL.

[This corrects the article DOI: 10.3389/fonc.2021.640166.].

Expression of pig7 gene in acute leukemia and its potential to modulate the chemosensitivity of leukemic cells.

We analyzed expression of p53-induced gene 7 (pig7), at the transcript level, in bone marrow samples from patients with de novo acute leukemia (AL) and normal controls by quantitative reverse transcription PCR (RT-PCR), and revealed a markedly decreased pig7 expression in the patient group, as well as in the relapsed/refractory patients compared with those at initial diagnosis. By endonuclease analysis, we detected only one form of pig7 transcript, i.e., small integral membrane protein of late endosome (simple), in AL patients. In addition, up-regulated pig7 expression could be detected in differentiated leukemic cells induced by drugs. Transient expression of pig7 in leukemic cells exhibited no evident effect on cell proliferation and differentiation, but could intensify inhibitory efficacy of etoposide (VP16) and daunorubicin (DNR). Conclusively, the present study provides the evidence that pig7 is a silenced gene affected by perturbed differentiation in acute leukemia and restoration of pig7 expression sensitizes leukemic cells to chemotherapeutic agents.

AML1-ETO interacts with Sp1 and antagonizes Sp1 transactivity through RUNT domain.

AML1-ETO fusion protein is observed in approximately 12% of acute myeloid leukemia. In the present research, we found that AML1-ETO is able to inhibit Sp1 transactivity. We also found that this inhibition of Sp1 transactivity by AML1-ETO is achieved by interaction between Sp1 and RUNT domain of AML1. AML1b is able to abrogate the inhibition of AML1-ETO. Since Sp1 is involved in hematopoietic cell differentiation, we proposed that AML1-ETO promotes leukemogenesis by blocking cell differentiation through inhibition of Sp1 transactivity.

Preparation of an ultrathin Pt electrocatalyst via a galvanic replacement reaction of electrodeposited CuCl for the oxidation of methanol in an alkaline medium.

An ultrathin Pt electrocatalyst is prepared by the electrodeposition of a thin and uniform CuCl semiconductor film on an Au electrode followed by a galvanic replacement reaction with K2PtCl4, which shows an ultrahigh Pt-mass specific electrocatalytic activity of 23.7 mA µgPt-1 for methanol oxidation in an alkaline medium.

TRPM8 activation improves energy expenditure in skeletal muscle and exercise endurance in mice.

Skeletal muscle serving as the major organ is responsible for energy expenditure and exercise endurance, which directly influence cardiometabolic risk factors. Transient receptor potential melastatin 8 (TRPM8), a Ca2+-permeable non-selective cation channel, plays vital roles in the regulation of various cellular functions. It has been reported that TRPM8 activation enhanced the energy metabolism of adipocytes. However, the involvement of TRPM8 in the energy metabolism of skeletal muscle remains unexplored. Our data revealed that TRPM8 was expressed in cultured C2C12 myocytes. Menthol treatment increased uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) expression in C2C12 myotubes through TRPM8 activation. Moreover, dietary menthol upregulated the expression of UCP1 and PGC1α in skeletal muscle of mice. In addition, dietary menthol enhanced exercise endurance and reduced blood lactic acid and triglycerides through TRPM8 activation. It is concluded that dietary menthol improves energy metabolism and exercise endurance by increasing UCP1 and PGC1α in skeletal muscles, suggesting dietary menthol might be a novel therapeutic approach for cardiometabolic diseases management and prevention.

Short interfering RNA targeting Net1 reduces the angiogenesis and tumor growth of in vivo cervical squamous cell carcinoma through VEGF down-regulation.

Net1, a guanine nucleotide exchange factor, is implicated in cancer cell invasion through activation of RhoA. However, there is still no report on the association between Net1 and cancer angiogenesis. The current study was designed to explore the role of Net1 in the angiogenesis of cervical squamous cell carcinoma (CSCC) and further observe the effects of Net1 short interfering RNA (siRNA) on the tumor growth. Net1 was overexpressed in CSCC samples (n=80), correlated with the cancer microvessel density (r=0.223, P=.026), and related to aggressive clinical behaviors, including depth of cervical wall invasion (P=.041), parametrial involvement (P=.037), lymph node metastasis (P=.021), and vascular invasion (P=.018). Human umbilical vein endothelial cells treated with supernatant of SiHa cells with Net1 siRNA showed significantly decreased proliferation (0.75±0.038 versus 1.0±0.015, P<.001), migration (39.3±6.5 versus 66.0±10.1, P=.019), and tube formation (13.5±3.05 versus 21.7±2.89, P=.030) compared with those human umbilical vein endothelial cells treated with normal SiHa cells supernatant. Net1 siRNA of SiHa decreased VEGF expression level (0.60±0.026 versus 0.78±0.031, P=.02). Furthermore, Net1 siRNA significantly reduced tumor growth (P=.037) and microvessel density (5.8±0.43 versus 3.4±0.55, P=.012) and decreased the expression level of VEGF (0.31±0.002 versus 0.39±0.004, P<.001) in CSCC. In conclusion, Net1 promotes the angiogenesis of CSCC, and siRNA targeting Net1 can effectively reduce the angiogenesis and thus inhibit the tumor growth of CSCC in vivo.

Risk of MDM2 SNP309 alone or in combination with the p53 codon 72 polymorphism in acute myeloid leukemia.

A single nucleotide polymorphism (SNP) in the promoter of MDM2 gene, SNP309 T>G (a T-G exchange at nucleotide 309 in the first intron), can increase the expression level of MDM2, thereby causing an impairment of p53 tumor suppressor activity. A G-C exchange at p53 codon 72 polymorphism results in a substitution of proline (Pro) for arginine (Arg) in the transactivation domain, which was shown to alter the primary structure of the p53 protein. Both polymorphisms have been implicated in cancer. To investigate whether that MDM2 SNP309 and p53 codon 72 polymorphism should be at least partially responsible for genetic susceptibility to acute myeloid leukemia (AML), both polymorphisms were determined in a case-control study consisting of 231 AML patients and 128 normal individuals. The MDM2 SNP309G allele was associated with increased risk of AML. Furthermore, the p53 codon 72 and MDM2 SNP309 polymorphisms did not associate with age of onset and any other clinical parameters studied. When the p53 and MDM2 polymorphisms were combined, no multiplicative joint effect between the MDM2 GG and p53 Pro/Pro genotypes exists in the risk of developing AML. These results suggest that the MDM2 SNP309 homozygous GG genotype may be a genetic susceptibility factor in the pathogenesis of AML.