Decline in Cancer Screening in Vulnerable Populations? Results of the EDIFICE Surveys.

BACKGROUND: We studied cancer screening over time and social vulnerability via surveys of representative populations. METHODS: Individuals aged 50-75 years with no personal history of cancer were questioned about lifetime participation in screening tests, compliance (adherence to recommended intervals [colorectal, breast and cervical cancer]) and opportunistic screening (prostate and lung cancer). RESULTS: The proportion of vulnerable/non-vulnerable individuals remained stable between 2011 and 2016. In 2011, social vulnerability had no impact on screening participation, nor on compliance. In 2014, however, vulnerability was correlated with less frequent uptake of colorectal screening (despite an organised programme) and prostate cancer screening (opportunistic), and also with reduced compliance with recommended intervals (breast and cervical cancer screening). In 2016, the trends observed in 2014 were substantiated and even extended to breast, colorectal and cervical cancer screening uptakes. Social vulnerability has an increasingly negative impact on cancer screening attendance. The phenomenon was identified in 2014 and had expanded by 2016. CONCLUSION: Although organised programmes have been shown to ensure equitable access to cancer screening, this remains a precarious achievement requiring regular monitoring. Further studies should focus on attitudes of vulnerable populations and on ways to improve cancer awareness campaigns.

Colon Cancer Screening Programs: Impact of an Organized Screening Strategy Assessed by the EDIFICE Surveys.

BACKGROUND: The aim of EDIFICE surveys is to improve insight into the behavior of the French population with regard to cancer prevention and participation in screening programs. Via the colorectal cancer screening program, all average-risk individuals in the 50-74-year age group are invited every 2 years to do a guaiac-based or, since April 2015, an immunochemical fecal occult blood test. METHODS: The fifth edition of the nationwide observational survey was conducted by phone interviews using the quota method. A representative sample of 1299 individuals with no history of cancer (age, 50-74 years) was interviewed between 22 November and 7 December 2016. The present analysis focuses on minimum lifetime uptake of screening tests, compliance to recommended repeat-screening intervals, and reasons for non-participation. RESULTS: In 2016, 64% survey participants had been screened at least once and 38% had been screened in the previous 2 years, suggesting a trend towards increasing participation rates, particularly in the younger age categories and among men. The 2016 data also suggest that the newly implemented FIT-based screening program has been well perceived by the population. Up to one in four individuals cited "no risk factors" as the reason for not undergoing screening. This reveals ignorance of the fact that the colorectal cancer screening program actually targets all average-risk individuals in a given age group, without individual risk factors. CONCLUSION: We suggest the next step should be dedicated to educational approaches to explain exactly what screening involves and to persuasive messages targeting those who to date have remained unreceptive to information campaigns.

Perception of Lung Cancer Risk: Impact of Smoking Status and Nicotine Dependence.

BACKGROUND: The general population is nowadays well aware that tobacco smoking dramatically increases the risk of developing lung cancer. We hypothesized that a personal history of smoking and the level of nicotine dependence in current smokers may affect the perception of this risk among healthy individuals. METHODS: The fourth French nationwide observational survey, EDIFICE 4, was conducted by telephone among a representative sample of individuals (N = 1602) aged between 40 and 75 years. Interviewees were asked about their smoking habits, perception of the risk of lung cancer, and nicotine dependence (Fagerström test). RESULTS: Regardless of their smoking status or level of nicotine dependence, the majority (96%) of our study population (N = 1463) acknowledged that tobacco smoking is a major risk factor for lung cancer. For 34% of all respondents, smoking ≤ 10 cigarettes per day does not carry any risk of lung cancer. Only half the current smokers considered themselves to be at higher risk of lung cancer than the average-risk population. The majority of current cigarette smokers with a nicotine dependence considered themselves to be at higher risk for lung cancer while only 37% of non-nicotine-dependent individuals had the same perception (P < 0.01). Current smokers were more likely to consider a screening examination than former smokers and never-smokers. However, the intention to undergo screening was not significantly affected by the level of nicotine dependence. CONCLUSIONS: Awareness campaigns may first have to overcome misconceptions about light smoking and, secondly, to target specific populations (heavy smokers, those with a long history, highly dependent smokers).

Fluctuating Behavior of the French Population in Cancer Screening: 5th Edition of the EDIFICE Survey.

BACKGROUND: The EDIFICE surveys have assessed cancer screening behavior in the French population since 2005. METHODS: The 2016 edition was conducted among a representative sample of 1501 individuals (age, 50-75 years). The current analysis focuses on breast, colorectal, prostate, lung, and cervical cancer screening. RESULTS: The rate of women (50 to 74 years) declaring having had at least one breast cancer screening test in their lifetime remained stable and high between 2005 and 2016. Compliance with recommended screening intervals improved between 2005 and 2011 from 75 to 83%, respectively, then decreased significantly to 75% in 2016 (P = 0.02). Uptake of at least one lifetime colorectal cancer screening test procedure declared (individuals aged 50-74 years) increase from 25% in 2005 to 59% in 2011, stabilized at 60% in 2014, then reached 64% in 2016. Opportunistic prostate cancer screening (men aged 50-75 years) rose between 2005 and 2008 from 36 to 49%, plateaued until 2014 then dropped to 42% in 2016. The proportion of women aged 50-65 declaring having undergone one cervical cancer screening test dropped significantly between 2014 and 2016 from 99 to 94% (P < 0.01). Lastly, 11% of our survey population in 2014 and 2016 (55-74 years) declared having already undergone lung cancer screening. CONCLUSION: Cancer screening behavior fluctuates in France, regardless of the context, i.e., organized programs or opportunistic screening. This observation highlights the need for constant analysis of population attitudes to optimize public awareness campaigns.

Awareness and Misconceptions of Breast Cancer Risk Factors Among Laypersons and Physicians.

BACKGROUND: Primary prevention of cancer relies on awareness of and consequent identification of risk factors. We investigated knowledge of breast cancer risk factors not only among laywomen but also among female physicians. METHODS: The EDIFICE 4 nationwide observational survey was conducted by phone interviews of a representative female population (737 laywomen and 105 female physicians) aged 40-75 years, using the quota method. This analysis focuses on spontaneous replies to the question "In your opinion, what are the five main risk factors that increase the risk of breast cancer?". RESULTS: Heredity/Family history of breast cancer was the most widely recognized risk factor in both study populations (98.1% physicians vs. 54.2% laywomen; P ≤ 0.01). Smoking (19.0 and 17.5%) and alcohol consumption (3.8 and 5.5%) were among the lifestyle risk factors that were cited by similar proportions of physicians and laywomen, respectively. Other established risk factors were however very rarely cited by either physicians or laywomen, e.g., Exposure to medical radiation (4.8 vs. 0.4%, respectively; P ≤ 0.05) or not cited at all, i.e., Benign mastopathy and Personal history of breast cancer. CONCLUSION: This survey highlights a number of misconceptions relating to behavioral risk factors for breast cancer, including the relative impact of alcohol and tobacco consumption and the importance of menopausal status. The limited awareness of the risk related to Exposure to medical radiation, Benign mastopathy, or Personal history raises concern regarding compliance with national screening recommendations.

Women's participation in breast cancer screening in France--an ethical approach.

BACKGROUND: Breast cancer is a major public health challenge. Organized mammography screening (OS) is considered one way to reduce breast cancer mortality. EU recommendations prone mass deployment of OS, and back in 2004, France introduced a national OS programme for women aged 50-74 years. However, in 2012, participation rate was still just 52.7%, well short of the targeted 70% objective. In an effort to re-address the (in) efficiency of the programme, the French National Cancer Institute has drafted an expert-group review of the ethical issues surrounding breast cancer mammography screening. DISCUSSION: Prompted by emerging debate over the efficiency of the screening scheme and its allied public information provision, we keynote the experts' report based on analysis of epidemiological data and participation rate from the public health authorities. The low coverage of the OS scheme may be partly explained by the fact that a significant number of women undergo mammography outside OS and thus outside OS criteria. These findings call for further thinking on (i) the ethical principles of beneficence and non-malfeasance underpinning this public health initiative, (ii) the reasons behind women's and professionals' behavior, and (iii) the need to analyze how information provision to women and the doctor-patient relationship need to evolve in response to scientific controversy over the risks and benefits of conducting mammographic screening. SUMMARY: This work calls for a reappraisal of the provision of screening programme information. We advocate a move to integrate the points sparking debate over the efficiency of the screening scheme to guarantee full transparency. The perspective is to strengthen the respect for autonomy allowing women to make an informed choice in their decision on whether or not to participate.

[Mapping of the key oncology indicators available in France]. / Cartographie des principaux indicateurs disponibles en France dans le domaine du cancer.

BACKGROUND: Available data in the field of oncology in France are scattered due to the large number of available indicators and their sources. In order to facilitate identification and analysis of these indicators, the French National Cancer Institute (INCa) has mapped the main indicators available in oncology. METHODS: Mapping was based on the needs of various categories of potential users. Standardized interviews were conducted face-to-face or by email among representatives to determine their needs and expectations. The underlying data sources were also identified: databases, national surveys, websites. A first selection of indicators was proposed in the report entitled "La situation du cancer en France en 2009" ("The state of cancer in France in 2009") and was expanded. Data collection concerning indicators was performed among INCa correspondents for each theme. RESULTS: Several themes were defined: epidemiology, prevention and risk factors, screening, medical demography, health care offer, living conditions, costs and expenses, research. Data were classified according to: geographical coverage, age, gender, type of cancer, occupational categories. This information was collected for each indicator selected and was made available via the cancer data website (http://lesdonnees.e-cancer.fr). CONCLUSIONS: The available oncology indicators are numerous and scattered. Mapping can be a useful tool to facilitate access to these indicators. It should be regularly updated to reflect the most recent data.

Sargassum seaweed health menace in the Caribbean: clinical characteristics of a population exposed to hydrogen sulfide during the 2018 massive stranding.

BACKGROUND: Since 2011, there have been ongoing massive unexplained increases of sargassum seaweed strandings along the coastlines of Caribbean countries. The objective of our study was to describe the clinical characteristics of patients exposed to noxious emissions of decomposing sargassum seaweed. METHODS: This observational study included patients from January 2018 to December 2018 for complaints attributed to decomposing sargassum seaweed. History and geographical characteristics of sargassum seaweed strandings as well as detection of ambient air hydrogen sulfide (H2S) levels were documented during the inclusion period. FINDINGS: A total of 154 patients were included. Mean exposure period was 3 months. Neurological (80%), digestive (77%) and respiratory (69%) disorders were the most frequent reasons for medical visit. Temporal distribution of medical visits was related to history of strandings. Geographical origins of patients were consistent with the most impacted areas of strandings as well as the most elevated ambient air H2S levels. INTERPRETATION: The toxicological syndrome induced by sargassum seaweed exposure is close to the toxidrome associated with acute H2S exposure in the range of 0-10 ppm. Our study suggests that patients living in massive stranding areas may be exposed to H2S > 5 ppm for 50 days per year.

[Colorectal cancer screening programme in France, role of the National Institute of Cancer]. / Dépistage organisé du cancer colorectal en France: rôle de l'Institut National du Cancer.

With almost 37,500 new cases per year and 17,000 deaths, colorectal cancer represents a major public health problem in France. A new stage in the fight against this cancer should be marked in 2009 with the widespread implementation of the colorectal cancer screening programme over the whole of the French territory. This population-based screening programme targets an eligible population of 16 million persons. The evaluation of the first 23 pilot districts allowed a standardization of the main quality and efficacy indicators. The implementation of the colorectal cancer screening programme relies on monitoring centres, usually one per district, set up for the national breast cancer screening programme. The programme refers to quality assurance guidelines and includes explicit policy with specified age categories, method, and interval for screening. A national screening training programme for newly districts joining the programme was implemented. A small number of laboratories have been selected for the programme on quality criteria. The French National Cancer Institute contributes to organization, information, guidelines, and research. The replacement of the guaiac test used in the French programme by an immunochemical test should be effective in the next few years.

Breast cancer screening: Impact on care pathways.

BACKGROUND: Controversy persists concerning screening programs (SPs), related to a potential risk of overdiagnosis or the impact on survival. One of the main questions to be addressed concerns the aggressiveness of the related treatments. METHODS: Using the "Cancer Cohort," a national-based cohort (medico-administrative database), all women between the ages of 50 and 74 years and treated in 2014 for incident breast cancer were compared, according to whether their diagnosis was made following a mammogram performed within the framework of the SP (SP group) or outside it (NSP group). RESULTS: A total of 23 788 women were identified: 13 530 (57%) in the SP group and 10 258 (43%) in the NSP group. The women in the SP group had a higher rate of in situ or localized invasive breast cancer. They had a higher rate of breast-conserving surgery (82% vs 70%), and a lower rate of chemotherapy (34% vs 53%). These findings were observed irrespective of the stage. They had a higher rate of pathways involving breast-conserving surgery followed by radiotherapy. Among women with metastatic cancer, those in the SP group had a lower proportion of liver, lung, brain, and bone metastases, and a higher proportion of lymph node metastases (other than axillary), irrespective of the time to onset of the metastases. CONCLUSION: The women in whom cancer was diagnosed following a mammogram performed in the context of the SP had less advanced cancer and less aggressive treatments. This observational study helps illustrate the benefit of the SP in France using a different approach.

Current and Former Smokers: Who Wants To Be Screened?

BACKGROUND: Lung cancer (LC) screening (LCS) with annual low-dose computed tomography scans has been seen to reduce the specific and overall mortality in selected populations. However, participation is key to successful screening programs. The EDIFICE (etude sur le dépistage des cancers et ses facteurs de compliance [survey on cancer screening and compliance factors]) nationwide observational surveys are used to assess behavior related to cancer screening programs in France. MATERIALS AND METHODS: Using comprehensive multivariate stepwise logistic regression analyses of data from current and former cigarette smokers, we sought to identify the explanatory factors associated with the intention to participate in an LCS program. RESULTS: Of the 1463 respondents with no personal history of cancer, 263 (36.4%) of the current cigarette smokers and 170 (26.3%) of the former cigarette smokers stated their willingness to participate in an LCS program. The explanatory factors differed between current cigarette smokers (already screened for LC: odds ratio [OR], 2.81; < 30 pack-years: OR, 2.69; intention to quit smoking: OR, 1.96; no social vulnerability: OR, 2.15) and former cigarette smokers (comorbidities: OR, 0.31). The usual eligibility criteria were not significantly explanatory. CONCLUSION: Our findings highlight the discrepancy that exists between target populations and individuals who actually intend to participate in a screening program for LC, with subsequent potential effects on the participation rates and, thus, on the efficacy of screening.

Cancer care and public health policy evaluations in France: Usefulness of the national cancer cohort.

BACKGROUND: In the context of the national Cancer Plans of France that have changed the healthcare landscape, it has become necessary to better document and assess the related actions, and to promote research and understanding. The national cancer cohort, an exhaustive population-based cohort, was set up on the basis of the National Health Data System (SNDS) by the French National Cancer Institute. OBJECTIVES: The aim is to describe the French national cancer cohort. METHODS: All people living in France (67 million population) with universal insurance coverage and diagnosed, treated or followed up for a cancer, such as survivors, are included and will be followed up for 25 years. It contains all healthcare consumptions and reimbursements (i.e. hospitalization, outpatient care, medication…) since 2010. Every year, around 650 000 new cases are included. RESULTS: From 2010 to 2015, 6.2 million subjects have been included. Most subjects were entered in 2010, in 2015 it concerned 0.6 million. In 2015, the median age was 65 [54-76]; 51% were women. The primary cancer organ could be attributed with certitude to 87% of the people. The most frequent locations were skin (16%), breast (15%), prostate (12%), colon-rectum (11%) and lung (9%). In 2015, 40% of included subjects underwent surgery for cancer, 16% chemotherapy at hospital and 11% at least one session of radiotherapy. CONCLUSION: Based on SNDS, the cancer cohort has been designed to study cancer care use in the short-, medium- and long-term, and evaluate healthcare and public health policies.

Beliefs and behavior regarding e-cigarettes in a large cross-sectional survey.

Although e-cigarette use is increasing dramatically, numerous concerns persist regarding toxicity and their role in smoking cessation. We assessed beliefs and behavior regarding e-cigarettes in an adult French population. The 4th French nationwide observational survey, EDIFICE 4, was conducted among representative samples of 1602 laypersons (age, 40-75 years) from 12 June-10 July 2014, using the quota method. Profile, beliefs and behavior were assessed by phone interviews of the participating lay population with no history of cancer (N = 1463). Tobacco use, nicotine dependence (Fagerström test) and e-cigarette use were assessed. E-cigarette users represented 6% of the study lay population. E-cigarette users regarded e-cigarettes as helpful for quitting tobacco smoking and reducing the risk of lung cancer. Current dual users (e-cigarettes + cigarettes) were more likely to attempt to quit than current exclusively cigarette smokers (odds ratio, 3.15 [1.74-5.70]), and to consider themselves at higher risk for lung cancer (OR 3.85 [2.47-5.99]). They also considered e-cigarette vapor to be less toxic than tobacco smoke in terms of both active and passive exposure. Dual users typically consider themselves at higher risk for cancer and intend to quit smoking. Physicians should be made aware of this specific sub-population for whom e-cigarettes may be a useful trigger in the smoking cessation process.

Care organization in oncology / Organisation des soins en cancérologie

Care organization in oncology. The health care organization for cancer patients has been built with the passing and current cancer plans, and the coordination of all the actions against cancer by the French national cancer institute. The authors describe the several phases of a patient pathway during and after cancer treatment, underline the importance of supporting good practice guidelines for health professionals, certification criteria and cancer authorization decrees for health care institutions, as well as coordination structures, and describe the specific organizations for children and elderly patients with cancer and for patients with rare cancers. Constant adaptation of the health care organization for cancer is necessary because of the rapid evolution of the treatments, as the development of ambulatory surgery and of oral chemotherapy in outpatients.

Organisation des soins en cancérologie. L'organisation des soins en cancérologie s'est structurée au fil des Plan cancer successifs et de la coordination par l'Institut national du cancer de toutes les actions de lutte contre le cancer. Sont décrits ici les différents temps du parcours d'un malade atteint de cancer, pendant et au décours de son traitement, l'encadrement des pratiques des professionnels de santé par les référentiels nationaux de bonne pratique, l'encadrement règlementaire des établissements de santé délivrant les traitements des patients, les structures de coordination, les organisations spécifiques pour les enfants, les sujets âgés et les patients ayant des cancers rares. L'évolution rapide des traitements du cancer nécessite une adaptation constante de l'organisation des soins en cancérologie. C'est le cas pour la chirurgie ambulatoire et le développement des traitements médicaux du cancer (chimiothérapie et thérapie ciblée) par voie orale.

[Cancer screening in France: 10 years of analysis of behaviours by the EDIFICE surveys]. / Dépistage du cancer en France : 10 ans d'analyse des comportements par les enquêtes EDIFICE.

Accessibility to cancer screening in France has been facilitated by the implementation of organised programs (breast cancer and colorectal cancer) and by national recommendations (cervical cancer). Personal motivation may also trigger participation in prostate cancer screening. This paper proposes an overview of attitudes toward cancer screening among the general population over a period of more than 10 years and the perception of this behaviour by general practitioners. It is noteworthy that although certain cancer screening programmes, such as for breast cancer, are widely established throughout the population, uptake of others, such as for colorectal or prostate cancer, is contingent on sociological factors and vulnerability. Monitoring of compliance is thus all the more important since participation may be more acutely affected by the impact of social conditions and vulnerability in the current critical economic climate.

ERCC1 codon 118 polymorphism is a predictive factor for the tumor response to oxaliplatin/5-fluorouracil combination chemotherapy in patients with advanced colorectal cancer.

PURPOSE: The aim of our study was to assess whether the polymorphism of the nucleotide excision repair enzyme, excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1), had an effect on the tumor response in patients treated with standard chemotherapy regimens for a metastatic colorectal cancer. We have studied the synonymous polymorphism that causes a single nucleotide change C to T at codon 118 converting a codon of common usage (AAC) to a less used codon (AAT), both coding asparagine. This change results in a decreased ERCC1 gene expression, which impairs repair activity. EXPERIMENTAL DESIGN: Ninety-one patients with a median age of 55.1 years treated for a metastatic colorectal cancer were included in our retrospective study. The ERCC1 polymorphism was analyzed in the normal tissue of all patients. RESULTS: Twenty (22%) were homozygous for AAC codon (C/C genotype), 30 were (33%) homozygous for AAT codon (T/T genotype), and 41 (45%) were heterozygous (C/T genotype). The objective response rate to oxaliplatin in combination with 5-fluorouracil (5-FU) was significantly higher in the T/T genotype group compared with the C/T and the C/C genotype groups (61.9%, 42.3%, and 21.4%, respectively; P = 0.018). By contrast, no significant difference was observed when patients were treated with either 5-FU alone (45%, 29.2%, and 33.3%, respectively; P = 0.407) or in combination with irinotecan (46.1%, 25.0%, and 27.3%, respectively; P = 0.305). CONCLUSIONS: Our observations allowed us to define the first useful predictive criterion for oxaliplatin/5-FU response in patients with metastatic colorectal cancer.

[Ascites due to portal hypertension from breast cancer- related metastatic liver infiltration]. / Ascite liée à une hypertension portale secondaire à une infiltration hépatique sinusoïdale d'un cancer du sein.

Ascites in patients with breast cancer is uncommon. We report the case of a 70-year-old woman with breast cancer and ascites caused by portal hypertension due to metastatic liver infiltration. There was no evidence of peritoneal carcinomatosis and the prothrombin index was normal. Portal hypertension was confirmed by increased hepatic venous pressure gradient. Histological examination of a liver biopsy obtained by the transjugular route demonstrated infiltration by malignant cells from the breast tumor. This case shows that, infiltration of the liver by metastases from breast cancer may lead to ascites due to portal hypertension, even in the absence of hepatic failure.

Polyethylene glycol and prevalence of colorectal adenomas.

BACKGROUND AND AIM: Dietary polyethylene glycol (PEG) is extraordinarily potent in the chemoprevention of experimental colon carcinogenesis. PEG is used to treat constipation in France and in the USA. French laxatives include Forlax (PEG4000), Movicol and Transipeg (PEG3350), and Idrocol (pluronic F68). This study tests the hypothesis that use of a PEG-based laxative might reduce the prevalence of colorectal tumors. METHODS: In this population-based study, consecutive patients attending for routine total colonoscopy were enrolled during four months by the gastroenterologists of Indre-et-Loire. They were asked if they had previously taken a laxative or a NSAID. Age, gender, previous polyps, family history of colorectal cancer, constipation, digestive symptoms were also recorded. Tumors found during colonoscopy were categorized histologically. RESULTS: Records from 1165 patients fulfilled the inclusion criteria, 607 women and 498 men, mean age 58.3. Among those, 813 had no tumor, 329 had adenomas, and 23 had carcinomas. In a univariate analysis, older age, male gender, lack of digestive symptom, and previous polyps were more common in patients with colorectal tumors. In contrast, previous Forlax intake was more common in tumor-free patients (odds ratio (OR) any use/no use, 0.52; 95% confidence interval, 0.27-0.94). More people used Forlax, which contains a higher dose of PEG than the other PEG-laxatives, whose ORs were smaller than one, but did not reach significance. In multivariate analysis, older age and male gender were associated with higher risk, and NSAIDs use with lower risk, of colorectal tumors. CONCLUSION: Forlax users had a halved risk of colorectal tumors in univariate analysis, which suggests that PEG may prevent carcinogenesis.

Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer.

The aim of our study was to assess the relationship between colorectal tumor responsiveness to irinotecan and microsatellite instability (MSI), a feature of colorectal tumors with DNA mismatch repair defect. Seventy-two patients with metastatic colorectal cancer were included in our retrospective study. A complete response to irinotecan was observed in 1 patient and a partial response in 10 patients, whereas 61 patients did not respond to this treatment. We analyzed the protein expression of hMLH1, hMSH2, and BAX by immunohistochemistry, determined the MSI phenotype, and looked for mutations in the coding repeats located in the transforming growth factor beta-RII, BAX, hMSH3, and hMSH6 genes. All 44 tumors analyzed expressed detectable levels of hMLH1; 1 tumor lacked hMSH2 staining, whereas 4 tumors showed a marked decrease in BAX expression. A better response to irinotecan was observed in the patients whose tumors have lost BAX expression (P < 0.001). Among the 7 tumors that displayed a MSI-H phenotype, 4 responded to irinotecan, whereas only 7 of the 65 MSI-L/ microsatellite stable tumors did (P = 0.009). Seven of the 72 tumors had inactivating mutations in the coding repeats of the target genes. Three tumors displayed a mutation in the poly-A10 tract of the transforming growth factor beta-RII gene, associated with a 1-bp deletion in the poly-A8 tract of hMSH3 in one tumor and with a 1-bp deletion in the poly-G8 tract of BAX in another. Four tumors displayed mutations in the poly-G8 repeat of BAX, whereas 2 mutations in hMSH6 and hMSH3 were characterized. Among the 7 tumors with mutations in these target genes, 5 responded to irinotecan, whereas only 6 of the other 65 tumors did (P < 0.001), indicating that MSI-driven inactivation of target genes modifies tumor chemosensitivity. Our observations allowed us to define the first useful predictive criteria for irinotecan response in patients with colorectal cancer.