Salivary microbiome profiles of oral cancer patients analyzed before and after treatment.

BACKGROUND: Treating oral squamous cell carcinoma (OSCC) introduces new ecological environments in the oral cavity. This is expected to cause changes in the oral microbiome. The purpose of this study was to gain new information on the salivary microbiome of OSCC patients in order to improve the aftercare of OSCC patients. The aims of this study were to investigate possible changes in the salivary microbiome profiles of OSCC patients before and after cancer treatment and to compare these changes with the profiles of healthy controls. PATIENTS AND METHODS: Paraffin-stimulated whole saliva samples were collected, and the salivary flow rate was measured from 99 OSCC patients prior to surgical resection of the tumor and other adjuvant therapy. After treatment, 28 OSCC patients were re-examined with a mean follow-up time of 48 months. In addition, 101 healthy controls were examined and sampled. After DNA extraction and purification, the V4 hypervariable region of the 16S rRNA gene was amplified and sequenced using Illumina MiSeq. The merged read pairs were denoised using UNOISE3, mapped to zero-radius operational taxonomic units (zOTUs), and the representative zOTU sequences were assigned a taxonomy using HOMD. Descriptive statistics were used to study the differences in the microbial profiles of OSCC patients before and after treatment and in comparison to healthy controls. RESULTS: At baseline, the OSCC patients showed a higher relative abundance of zOTUs classified as Streptococcus anginosus, Abiotrophia defectiva, and Fusobacterium nucleatum. The microbial profiles differed significantly between OSCC patients and healthy controls (F = 5.9, p < 0.001). Alpha diversity of the salivary microbiome of OSCC patients was decreased at the follow-up, and the microbial profiles differed significantly from the pre-treatment (p < 0.001) and from that of healthy controls (p < 0.001). CONCLUSIONS: OSCC patients' salivary microbiome profile had a higher abundance of potentially pathogenic bacteria compared to healthy controls. Treatment of the OSCC caused a significant decrease in alpha diversity and increase in variability of the salivary microbiome, which was still evident after several years of follow-up. OSCC patients may benefit from preventive measures, such as the use of pre- or probiotics, salivary substitutes, or dietary counseling. Video Abstract.

Oil Absorbent Polypropylene Particles Stimulate Biodegradation of Crude Oil by Microbial Consortia.

Oil absorbent particles made from surface-modified polypropylene can be used to facilitate the removal of oil from the environment. In this study, we investigated to what extent absorbed oil was biodegraded and how this compared to the biodegradation of oil in water. To do so, we incubated two bacterial communities originating from the Niger Delta, an area subject to frequent oil spills, in the presence and absence of polypropylene particles. One community evolved from untreated soil whereas the second evolved from soil pre-exposed to oil. We observed that the polypropylene particles stimulated the growth of biofilms and enriched species from genera Mycobacterium, Sphingomonas and Parvibaculum. Cultures with polypropylene particles degraded more crude oil than those where the oil was present in suspension regardless of whether they were pre-exposed or not. Moreover, the community pre-exposed to crude oil had a different community structure and degraded more oil than the one from untreated soil. We conclude that the biodegradation rate of crude oil was enhanced by the pre-exposure of the bacterial communities to crude oil and by the use of oil-absorbing polypropylene materials. The data show that bacterial communities in the biofilms growing on the particles have an enhanced degradation capacity for oil.

Long-Term Analysis of Resilience of the Oral Microbiome in Allogeneic Stem Cell Transplant Recipients.

Stem cell transplantation (SCT) is associated with oral microbial dysbiosis. However, long-term longitudinal data are lacking. Therefore, this study aimed to longitudinally assess the oral microbiome in SCT patients and to determine if changes are associated with oral mucositis and oral chronic graft-versus-host disease. Fifty allogeneic SCT recipients treated in two Dutch university hospitals were prospectively followed, starting at pre-SCT, weekly during hospitalization, and at 3, 6, 12, and 18 months after SCT. Oral rinsing samples were taken, and oral mucositis (WHO score) and oral chronic graft-versus-host disease (NIH score) were assessed. The oral microbiome diversity (Shannon index) and composition significantly changed after SCT and returned to pre-treatment levels from 3 months after SCT. Oral mucositis was associated with a more pronounced decrease in microbial diversity and with several disease-associated genera, such as Mycobacterium, Staphylococcus, and Enterococcus. On the other hand, microbiome diversity and composition were not associated with oral chronic graft-versus-host disease. To conclude, dysbiosis of the oral microbiome occurred directly after SCT but recovered after 3 months. Diversity and composition were related to oral mucositis but not to oral chronic graft-versus-host disease.

Adaptive changes of sediment microbial communities associated with cleanup of oil spills in Nigerian mangrove forests.

The objectives of this study were to assess the influence on microbial communities resulting from i) the physical removal of free oil (pre-treatment or post-treatment), and ii) the level of oiling within a contaminated former mangrove forest. Sediment samples were collected before and after the removal of free oil. Before the process of remediation, a highly biodiverse mangrove microbiome which had adapted to history of recurring oil spills was observed. After removing the surface oil, the microbial diversity of the sediments reduced, with members of the phyla Firmicutes and Proteobacteria becoming dominant. This indicates that while water flushing reduced overall microbial diversity, it stimulated the growth of a more specialized bacterial community reported to be involved in hydrocarbon biodegradation. These results provide new insights on microbial communities and their succession in mangrove forest sediments, that will be useful for monitoring oil cleaning programs using water flushing to remove free oil.

The microbiome of dental and peri-implant subgingival plaque during peri-implant mucositis therapy: A randomized clinical trial.

AIM: To assess the microbial effects of mechanical debridement in conjunction with a mouthrinse on sites with peri-implant mucositis and gingivitis. MATERIALS AND METHODS: Eighty-nine patients with peri-implant mucositis were included in a double-blinded, randomized, placebo-controlled trial with mechanical debridement and 1-month use of either delmopinol, chlorhexidine (CHX), or a placebo mouthrinse. Submucosal and subgingival plaque samples of implants and teeth were collected at baseline and after 1 and 3 months, processed for 16S V4 rRNA gene amplicon sequencing, and analysed bioinformatically. RESULTS: The sites with peri-implant mucositis presented with a less diverse and less anaerobic microbiome. Exposure to delmopinol or CHX, but not to the placebo mouthrinse resulted in microbial changes after 1 month. The healthy sites around the teeth harboured a more diverse and more anaerobe-rich microbiome than the healthy sites around the implants. CONCLUSIONS: Peri-implant sites with mucositis harbour ecologically less complex and less anaerobic biofilms with lower biomass than patient-matched dental sites with gingivitis while eliciting an equal inflammatory response. Adjunctive antimicrobial therapy in addition to mechanical debridement does affect both dental and peri-implant biofilm composition in the short term, resulting in a less dysbiotic subgingival biofilm.

Reprocessing 16S rRNA Gene Amplicon Sequencing Studies: (Meta)Data Issues, Robustness, and Reproducibility.

High-throughput sequencing technology provides an efficient method for evaluating microbial ecology. Different bioinformatics pipelines can be used to convert 16S ribosomal RNA gene amplicon sequencing data into an operational taxonomic unit (OTU) table that is used to analyze microbial communities. It is important to assess the robustness of these pipelines, each with specific algorithms and/or parameters, and their influence on the outcome of statistical tests. Articles with publicly available datasets on the oral microbiome were searched for, and five datasets were retrieved. These were from studies on changes in microbiota related to smoking, oral cancer, caries, diabetes, or periodontitis. Next, the data was processed with four pipelines based on VSEARCH, USEARCH, mothur, and UNOISE3. OTU tables were rarefied, and differences in α-diversity and ß-diversity were tested for different groups in a dataset. Finally, these results were checked for consistency among these example pipelines. Of articles that deposited data, only 57% made all sequencing and metadata available. When processing the datasets, issues were encountered, caused by read characteristics and differences between tools and their defaults in combination with a lack of detail in the methodology of the articles. In general, the four mainstream pipelines provided similar results, but importantly, P-values sometimes differed between pipelines beyond the significance threshold. Our results indicated that for published articles, the description of bioinformatics methods and data deposition should be improved, and regarding reproducibility, that analysis of multiple subsamples is required when using rarefying as library-size normalization method.

Submucosal microbiome of peri-implant sites: A cross-sectional study.

AIM: To study the peri-implant submucosal microbiome in relation to implant disease status, dentition status, smoking habit, gender, implant location, implant system, time of functional loading, probing pocket depth (PPD), and presence of bleeding on probing. MATERIALS AND METHODS: Biofilm samples were collected from the deepest peri-implant site of 41 patients with paper points, and analysed using 16S rRNA gene pyrosequencing. RESULTS: We observed differences in microbial profiles by PPD, implant disease status, and dentition status. Microbiota in deep pockets included higher proportions of the genera Fusobacterium, Prevotella, and Anaeroglobus compared with shallow pockets that harboured more Rothia, Neisseria, Haemophilus, and Streptococcus. Peri-implantitis (PI) sites were dominated by Fusobacterium and Treponema compared with healthy implants and peri-implant mucositis, which were mostly colonized by Rothia and Streptococcus. Partially edentulous (PE) individuals presented more Fusobacterium, Prevotella, and Rothia, whereas fully edentulous individuals presented more Veillonella and Streptococcus. CONCLUSIONS: PPD, implant disease status, and dentition status may affect the submucosal ecology leading to variation in composition of the microbiome. Deep pockets, PI, and PE individuals were dominated by Gram-negative anaerobic taxa.

High biodiversity in a benzene-degrading nitrate-reducing culture is sustained by a few primary consumers.

A key question in microbial ecology is what the driving forces behind the persistence of large biodiversity in natural environments are. We studied a microbial community with more than 100 different types of species which evolved in a 15-years old bioreactor with benzene as the main carbon and energy source and nitrate as the electron acceptor. Using genome-centric metagenomics plus metatranscriptomics, we demonstrate that most of the community members likely feed on metabolic left-overs or on necromass while only a few of them, from families Rhodocyclaceae and Peptococcaceae, are candidates to degrade benzene. We verify with an additional succession experiment using metabolomics and metabarcoding that these few community members are the actual drivers of benzene degradation. As such, we hypothesize that high species richness is maintained and the complexity of a natural community is stabilized in a controlled environment by the interdependencies between the few benzene degraders and the rest of the community members, ultimately resulting in a food web with different trophic levels.

Manipulation of Saliva-Derived Microcosm Biofilms To Resemble Dysbiotic Subgingival Microbiota.

Periodontitis is a highly prevalent oral inflammatory disease triggered by dysbiotic subgingival microbiota. For the development of microbiome modulators that can reverse the dysbiotic state and reestablish a health-associated microbiota, a high-throughput in vitro multispecies biofilm model is needed. Our aim is to establish a model that resembles a dysbiotic subgingival microbial biofilm by incorporating the major periodontal pathogen Porphyromonas gingivalis into microcosm biofilms cultured from pooled saliva of healthy volunteers. The biofilms were grown for 3, 7, and 10 days and analyzed for their microbial composition by 16S rRNA gene amplicon sequencing as well as measurement of dipeptidyl peptidase IV (DPP4) activity and butyric acid production. The addition of P. gingivalis increased its abundance in saliva-derived microcosm biofilms from 2.7% on day 3 to >50% on day 10, which significantly reduced the Shannon diversity but did not affect the total number of operational taxonomic units (OTUs). The P. gingivalis-enriched biofilms displayed altered microbial composition as revealed by principal-component analysis and reduced interactions among microbial species. Moreover, these biofilms exhibited enhanced DPP4 activity and butyric acid production. In conclusion, by adding P. gingivalis to saliva-derived microcosm biofilms, we established an in vitro pathogen-enriched dysbiotic microbiota which resembles periodontitis-associated subgingival microbiota in terms of increased P. gingivalis abundance and higher DPP4 activity and butyric acid production. This model may allow for investigating factors that accelerate or hinder a microbial shift from symbiosis to dysbiosis and for developing microbiome modulation strategies.IMPORTANCE In line with the new paradigm of the etiology of periodontitis, an inflammatory disorder initiated by dysbiotic subgingival microbiota, novel therapeutic strategies have been proposed targeting reversing dysbiosis and restoring host-compatible microbiota rather than eliminating the biofilms unselectively. Thus, appropriate laboratory models are required to evaluate the efficacy of potential microbiome modulators. In the present study, we used the easily obtainable saliva as an inoculum, spiked the microcosm biofilms with the periodontal pathogen Porphyromonas gingivalis, and obtained a P. gingivalis-enriched microbiota, which resembles the in vivo pathogen-enriched subgingival microbiota in severe periodontitis. This biofilm model circumvents the difficulties encountered when using subgingival plaque as the inoculum and achieves microbiota in a dysbiotic state in a controlled and reproducible manner, which is required for high-throughput and large-scale evaluation of strategies that can potentially modulate microbial ecology.

Dysbiosis of the Oral Ecosystem in Severe Congenital Neutropenia Patients.

PURPOSE: To decipher the underlying immunological mechanisms in predisposition to oral microbial dysbiosis in severe congenital neutropenia (SCN) patients. EXPERIMENTAL DESIGN: Ten SCN patients (5-23 years old) and 12 healthy controls (5-22 years old) are periodontally examined and provided saliva, subgingival plaque, and gingival crevicular fluid (GCF) samples. The SCN patients received oral hygiene therapy and are re-evaluated after 6 months. Antimicrobial peptides HPN1-3 and LL-37 are assessed in saliva by ELISA. Concentration of 30 cytokines is measured in saliva and GCF by human 30-plex panel, while bacterial profiles of saliva and subgingival plaque are assessed using 16S rDNA amplicon sequencing. RESULTS: There is no significant difference in salivary HPN1-3 and LL-37 concentration between the SCN patients and controls. At baseline, clinical, immunological, and microbiological parameters of the patients are indicative of oral ecological dysbiosis. The SCN patients have significantly higher bleeding on probing (BOP)%, GCF volume, and cytokine levels, high bacterial load with low bacterial diversity in saliva. The associations between the microbiome and immunological parameters in the SCN patients differ from those in the healthy individuals. CONCLUSIONS AND CLINICAL RELEVANCE: SCN patients have a dysregulated immune response toward commensal oral microbiota, which could be responsible for the observed clinical and microbiological signs of dysbiosis.

Microbial changes in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients.

The aim of this prospective, two center study was to investigate the dynamics of the microbial changes in relation to the development of ulcerative oral mucositis in autologous SCT (autoSCT) recipients. Fifty-one patients were diagnosed with multiple myeloma and treated with high-dose melphalan followed by autoSCT. They were evaluated before, three times weekly during hospitalization, and three months after autoSCT. At each time point an oral rinse was collected and the presence or absence of ulcerative oral mucositis (UOM) was scored (WHO scale). Oral microbiome was determined by using 16S rRNA amplicon sequencing and fungal load by qPCR. Twenty patients (39%) developed UOM. The oral microbiome changed significantly after autoSCT and returned to pre-autoSCT composition after three months. However, changes in microbial diversity and similarity were more pronounced and rapid in patients who developed UOM compared to patients who did not. Already before autoSCT, different taxa discriminated between the 2 groups, suggesting microbially-driven risk factors. Samples with high fungal load (>0.1%) had a significantly different microbial profile from samples without fungi. In conclusion, autoSCT induced significant and reversible changes in the oral microbiome, while patients who did not develop ulcerative oral mucositis had a more resilient microbial ecosystem.

Limited added value of fungal ITS amplicon sequencing in the study of bovine abortion.

Bovine mycotic abortion is sporadic and caused by different ubiquitous and opportunistic fungi. Recently, a broad spectrum of bacterial opportunists involved in bovine abortion was revealed by 16S rRNA gene amplicon sequencing. We hypothesized that fungal organisms potentially involved in bovine abortion also might remain undetected by conventional culture. In this retrospective study, we therefore applied fungal internal transcribed spacer 2 (ITS2) region amplicon sequencing to 74 cases of bovine abortion submitted to our diagnostic service. The investigation was complemented by fungal culture and, retrospectively, by data from bacteriological, virological and parasitological analyses and histopathological examination of placentas. Fungal DNA was found in both the placentas and abomasal contents, with 92 fungal genera identified. In 18 cases, >75% of the reads belonged to one specific fungal genus: Candida (n = 7), Malassezia (n = 4), Cryptococcus (n = 3), unidentified Capnodiales (n = 3), Actinomucor (n = 1), Cystofilobasidium (n = 1), Penicillium (n = 1), Verticillum (n = 1) and Zymoseptoria (n = 1) with one case harboring two different genera. By culture, in contrast, fungal agents were detected in only 6 cases. Inflammatory and/or necrotizing lesions were found in 27/40 histologically assessed placentas. However, no lesion-associated fungal structures were detected in HE- and PAS-stained specimens. Complementary data revealed the presence of one or more non-fungal possible abortifacient: Chlamydiales, Coxiella burnetii, Leptospira spp., Campylobacter fetus subsp. fetus, Streptococcus uberis, Escherichia coli, Streptococcus pluranimalium, Bacillus licheniformis, Campylobacter fetus subsp. fetus, Serratia marcescens, Trueperella pyogenes, Schmallenbergvirus, Neospora caninum. The mycobiota revealed by sequencing did not differ between cases with or without a possible infectious etiology. Our study suggests that amplicon sequencing of the ITS2 region from DNA isolated from bovine abortion does not provide additional information or new insight into mycotic abortion and without complementary analyses may easily lead to a false interpretation of the role of fungal organisms in bovine abortion.

Subgingival microbiome of rheumatoid arthritis patients in relation to their disease status and periodontal health.

OBJECTIVE: Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases that share common risk factors. However, the bidirectional relationship between RA and periodontal disease is not fully understood. This study was undertaken to describe the bacterial component of the subgingival microbiome in RA patients and to relate this to RA disease activity and periodontal status. METHODS: Patients with chronic established RA (N = 78) were periodontally examined and their subgingival plaque samples were collected; their clinical and laboratory data on RA status and medication were obtained from medical records. Bacterial DNA was quantified by universal 16S rDNA qPCR, and Porphyromonas gingivalis by species-specific qPCR. For microbiome assessment, 16S rDNA amplicon sequencing was performed. RESULTS: Active RA was diagnosed in 58% of the patients and periodontitis in 82% (mild: 9%, moderate: 55%, severe: 18%). P. gingivalis was present in 14% of the samples. Different levels of gingival bleeding, periodontal probing depth, RA disease status, prednisolone use and smoking were associated with significantly different microbiome compositions. Two subgingival microbial community types were discerned. CONCLUSION: In RA patients with active disease, anti-inflammatory medication as part of RA therapy was associated with better oral health status and a healthier subgingival microbiome compared to that of RA patients in remission, especially those in remission who were current smokers. RA patients in remission with current smoking status may particularly benefit from a systematic periodontal treatment program. The potential role of microbial community types in patient stratification and personalized therapy should be assessed in longitudinal studies.

Same Exposure but Two Radically Different Responses to Antibiotics: Resilience of the Salivary Microbiome versus Long-Term Microbial Shifts in Feces.

UNLABELLED: Due to the spread of resistance, antibiotic exposure receives increasing attention. Ecological consequences for the different niches of individual microbiomes are, however, largely ignored. Here, we report the effects of widely used antibiotics (clindamycin, ciprofloxacin, amoxicillin, and minocycline) with different modes of action on the ecology of both the gut and the oral microbiomes in 66 healthy adults from the United Kingdom and Sweden in a two-center randomized placebo-controlled clinical trial. Feces and saliva were collected at baseline, immediately after exposure, and 1, 2, 4, and 12 months after administration of antibiotics or placebo. Sequences of 16S rRNA gene amplicons from all samples and metagenomic shotgun sequences from selected baseline and post-antibiotic-treatment sample pairs were analyzed. Additionally, metagenomic predictions based on 16S rRNA gene amplicon data were performed using PICRUSt. The salivary microbiome was found to be significantly more robust, whereas the antibiotics negatively affected the fecal microbiome: in particular, health-associated butyrate-producing species became strongly underrepresented. Additionally, exposure to different antibiotics enriched genes associated with antibiotic resistance. In conclusion, healthy individuals, exposed to a single antibiotic treatment, undergo considerable microbial shifts and enrichment in antibiotic resistance in their feces, while their salivary microbiome composition remains unexpectedly stable. The health-related consequences for the gut microbiome should increase the awareness of the individual risks involved with antibiotic use, especially in a (diseased) population with an already dysregulated microbiome. On the other hand, understanding the mechanisms behind the resilience of the oral microbiome toward ecological collapse might prove useful in combating microbial dysbiosis elsewhere in the body. IMPORTANCE: Many health care professionals use antibiotic prophylaxis strategies to prevent infection after surgery. This practice is under debate since it enhances the spread of antibiotic resistance. Another important reason to avoid nonessential use of antibiotics, the impact on our microbiome, has hardly received attention. In this study, we assessed the impact of antibiotics on the human microbial ecology at two niches. We followed the oral and gut microbiomes in 66 individuals from before, immediately after, and up to 12 months after exposure to different antibiotic classes. The salivary microbiome recovered quickly and was surprisingly robust toward antibiotic-induced disturbance. The fecal microbiome was severely affected by most antibiotics: for months, health-associated butyrate-producing species became strongly underrepresented. Additionally, there was an enrichment of genes associated with antibiotic resistance. Clearly, even a single antibiotic treatment in healthy individuals contributes to the risk of resistance development and leads to long-lasting detrimental shifts in the gut microbiome.

Proteins and peptides in parotid saliva of irradiated patients compared to that of healthy controls using SELDI-TOF-MS.

BACKGROUND: Radiotherapy to the head and neck area damages the salivary glands. As a consequence hyposalivation may occur, but also the protein composition of saliva may be affected possibly compromising oral health. The aim of our study was to compare the relative abundance of proteins and peptides in parotid saliva of irradiated patients to that of healthy controls. METHODS: Using Lashley cups and citric acid, saliva from the parotid glands was collected from nine irradiated patients and ten healthy controls. The samples were analyzed with SELDI-TOF-MS using a NP20 and IMAC-30 chip in the molecular weight range of 1-30 kDa. RESULTS: On the NP20 chip 61 (out of 217) and on the IMAC-30 chip 32 (out of 218) peaks differed significantly in intensity between the saliva of the irradiated patients and healthy controls. 55 % of the significant peaks showed higher intensity and 45 % showed lower intensity in the saliva of irradiated patients. The peaks may represent, amongst others, the salivary proteins lysozyme, histatins, cystatin, protein S100 and PRP's. CONCLUSIONS: Large differences were found in the relative abundance of a wide range of proteins and peptides in the parotid saliva of irradiated patients compared to healthy controls.

A protein prioritization approach tailored for the FA/BRCA pathway.

Fanconi anemia (FA) is a heterogeneous recessive disorder associated with a markedly elevated risk to develop cancer. To date sixteen FA genes have been identified, three of which predispose heterozygous mutation carriers to breast cancer. The FA proteins work together in a genome maintenance pathway, the so-called FA/BRCA pathway which is important during the S phase of the cell cycle. Since not all FA patients can be linked to (one of) the sixteen known complementation groups, new FA genes remain to be identified. In addition the complex FA network remains to be further unravelled. One of the FA genes, FANCI, has been identified via a combination of bioinformatic techniques exploiting FA protein properties and genetic linkage. The aim of this study was to develop a prioritization approach for proteins of the entire human proteome that potentially interact with the FA/BRCA pathway or are novel candidate FA genes. To this end, we combined the original bioinformatics approach based on the properties of the first thirteen FA proteins identified with publicly available tools for protein-protein interactions, literature mining (Nermal) and a protein function prediction tool (FuncNet). Importantly, the three newest FA proteins FANCO/RAD51C, FANCP/SLX4, and XRCC2 displayed scores in the range of the already known FA proteins. Likewise, a prime candidate FA gene based on next generation sequencing and having a very low score was subsequently disproven by functional studies for the FA phenotype. Furthermore, the approach strongly enriches for GO terms such as DNA repair, response to DNA damage stimulus, and cell cycle-regulated genes. Additionally, overlaying the top 150 with a haploinsufficiency probability score, renders the approach more tailored for identifying breast cancer related genes. This approach may be useful for prioritization of putative novel FA or breast cancer genes from next generation sequencing efforts.

Variation in the human TP53 gene affects old age survival and cancer mortality.

Longevity may depend on a balance between tumor suppression and tissue renewal mechanisms [Campisi, J., 2003. Cancer and ageing: rival demons? Nat. Rev. Cancer 3 (5), 339-349]. Mice with constitutively activated p53 are almost cancer free but their life span is reduced and accompanied by early tissue atrophy [Tyner et al., 2002. p53 mutant mice that display early ageing-associated phenotypes. Nature 415 (6867) 45-53]. Replacement of arginine (Arg) by proline (Pro) at position 72 of human p53 decreases its apoptotic potential [Dumont et al., 2003. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat. Genet. 33 (3), 357-365] providing a tool to test for a similar trade-off in humans. Using a formal meta-analysis of the published literature we show that carriers of the TP53 codon 72 Pro/Pro genotype have an increased cancer risk compared to Arg/Arg carriers (p<0.05). Next, in a prospective study of 1226 people aged 85 years and over we show that carriers of the Pro/Pro genotype have a 41% increased survival (p = 0.032) despite a 2.54 fold increased (p = 0.007) proportional mortality from cancer. It is suggested that human p53 protect against cancer but at a cost of longevity.