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C Bonaïti-Pellié

Publications and source records attributed to C Bonaïti-Pellié.

At least 19 recordsLinked to original sources
PubMed2006

[Identification and management of HNPCC syndrome (hereditary non polyposis colon cancer), hereditary predisposition to colorectal and endometrial adenocarcinomas].

BACKGROUND: The HNPCC syndrome (hereditary nonpolyposis colon cancer) is an inherited condition defined by clinical and genealogical information, known as Amsterdam criteria. In about 70% of cases, HNPCC syndrome is caused by germline mutations in MMR genes, leading to microsatellite instability of tumor DNA (MSI phenotype). Patients affected by the disease are at high risk for colorectal and endometrial carcinomas, but also for small intestine, urothelial, ovary, stomach and biliary tract carcinomas. HNPCC syndrome is responsible for 5% of colorectal cancers. Identification and management of this disease are part of a multidisciplinary procedure. METHODS: Twelve experts have been mandated by the French Health Ministry to analyze and synthesize their consensus position, and the resulting document has been reviewed by an additional group of 4 independent experts. MAIN RECOMMENDATIONS: The lack of sensitivity of Amsterdam criteria in recognizing patients carrying a MMR germline mutation led to an enlargement of these criteria for the recruitment of possible HNPCC patients, and to a 2-steps strategy, asking first for a tumor characterization according to MSI phenotype, especially in case of early-onset sporadic cases. The identification of germline MMR mutations has no major consequence on the cancer treatments, but influences markedly the long-term follow-up and the management of at-risk relatives. Gene carriers will enter a follow-up program regarding their colorectal and endometrial cancer risks, but other organs being at low lifetime risk, no specific surveillance will be proposed.

Adenocarcinoma↗
PubMed2001

Possible relationship between the van der Woude syndrome (vWS) locus and nonsyndromic cleft lip with or without cleft palate (NSCL/P).

Cleft lip with or without cleft palate (CL/P) is one of the most common congenital malformations in humans occurring with a birth prevalence of approximately 1:1,000. CL/P may be part of a defined syndrome, sequence or association, although most individual or familial cases present as an isolated (nonsyndromic) malformation (NSCL/P). Inheritance is generally regarded as multigenic although, in some families, NSCL/P seemingly segregates as a monogenic trait. On the other hand, van der Woude syndrome (vWS) is a rare autosomal dominant with cardinal features of lower-lip pits (LLP) and CL/P or cleft palate (alone). Since none of these traits is present in all mutation carriers, some individual or familial vWS cases, especially those lacking LLP, are indiscernible from NSCL/P, raising the question whether allelic variation at the vWS locus could underlie NSCL/P. This question was addressed using parametric linkage (LOD score) analysis in 21 multiplex NSCL/P families based on a tightly linked microsatellite marker (D1S3753), and nonparametric analysis using the transmission/disequilibrium test (GTDT) in 106 NSCL/P triads and selecting markers D1S205, D1S491, and D1S3753. No evidence for linkage of NSCL/P to vWS was found on the 21 families using the LOD score approach. In contrast, TDT yielded a significant P value of 0.04 for D1S205, supporting involvement of vWS in NSCL/P in a complex, modifying/polygenic manner rather than as a monogenic/major disease locus.

Alleles↗
PubMed2001

Family cancer history and risk of childhood acute leukemia (France).

OBJECTIVE: A case-control study was carried out to investigate the role of a family history of solid tumor or hematologic neoplasm in the etiology of childhood acute leukemia. METHODS: Family cancer history in first- and second-degree relatives was compared in 279 incident cases (242 cases of acute lymphocytic leukemia and 37 of acute myeloid leukemia) and 285 controls. Recruitment was stratified by age, gender, hospital, area of residence, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. RESULTS: A significant association between childhood acute leukemia and a family history of hematologic neoplasm (OR = 2.7, confidence interval (CI) = 1.1-6.9) was found. This association was particularly clear-cut when the cases were restricted to acute myeloid leukemia (OR = 13.3, CI = 2.5-70.9). Childhood acute leukemia was associated with a family history of solid tumor (OR = 1.5, CI = 1.0-2.2), and elevated odds ratios were observed for family history of gastrointestinal cancer and melanoma. Those results are most unlikely to be explained by socioeconomic status and familial structure, which were very similar for the cases and controls. Differential misclassification is also unlikely for the first-degree relatives, even though it is difficult to rule it out for the second-degree relatives' history. CONCLUSION: The present study supports the hypothesis that a family history of cancer may be a risk factor for childhood acute leukemia.

Acute Disease↗
PubMed2001

Nineteen years of national screening for congenital hypothyroidism: familial cases with thyroid dysgenesis suggest the involvement of genetic factors.

Although a few familial forms of congenital hypothyroidism (CH) due to thyroid dysgenesis (TD) have been reported, this disorder is usually considered to be sporadic. Recently, we reported that 2% of CH patients with TD have a positive familial history. The aim of this study was to describe the clinical characteristics of these familial cases and to compare them with sporadic cases. We used the French national population-based registry of the first 19-yr screening program, which included 14,416,428 screened neonates with a 100% recovery rate. Familial history of CH with TD was investigated by means of a questionnaire sent to the pediatricians (n = 592) who provided ongoing clinical care for the 4049 CH patients detected during this period, including 2863 CH cases due to TD. Information was obtained from 73% of these pediatricians who were following up 2472 CH patients with TD (86%). In all, 67 patients with a positive family history of CH with TD were referred, belonging to 32 multiplex families (i.e. including at least 2 affected members). Families were identified with ectopic gland (n = 12), athyreosis (n = 7), or both (n = 13). Comparison of familial with isolated cases showed a similar etiological diagnosis distribution of CH (40% vs. 33% for athyreosis and 60% vs. 67% for ectopic thyroid gland, respectively), whereas a significantly lower predominance of females was found in familial than in isolated cases (1.4 vs. 2.7; P < 0.03). Extrathyroidal congenital malformations were found with a similarly higher incidence in familial and isolated CH populations compared with the general population (respectively, 9% and 8.2% vs. 2.5%). In conclusion, although familial cases represent a minority of cases of congenital hypothyroidism caused by thyroid dysgenesis, they were observed in a significantly higher proportion (>15-fold) than would be expected from chance alone. This familial clustering, including athyreosis and ectopic thyroid gland, strongly suggests that genetic factors could be involved in thyroid dysgenesis with a common underlying mechanism for both etiological groups. Moreover, the high proportion of extrathyroidal congenital malformations in a population affected by CH due to TD suggests that the potential genetic factors involved in thyroid gland organogenesis are also involved in the development of other organs.

Congenital Hypothyroidism↗
PubMed2000

P53 germline mutations in childhood cancers and cancer risk for carrier individuals.

The family history of cancer in children treated for a solid malignant tumour in the Paediatric Oncology Department at Institute Gustave-Roussy, has been investigated. In order to determine the role of germline p53 mutations in genetic predisposition to childhood cancer, germline p53 mutations were sought in individuals with at least one relative (first- or second-degree relative or first cousin) affected by any cancer before 46 years of age, or affected by multiple cancers. Screening for germline p53 mutation was possible in 268 index cases among individuals fulfilling selection criteria. Seventeen (6.3%) mutations were identified, of which 13 were inherited and four were de novo. Using maximum likelihood methods that incorporate retrospective family data and correct for ascertainment bias, the lifetime risk of cancer for mutation carriers was estimated to be 73% for males and nearly 100% for females with a high risk of breast cancer accounting for the difference. The risk of cancer associated with such mutations is very high and no evidence of low penetrance mutation was found. These mutations are frequently inherited but de novo mutations are not rare.

Adult↗
PubMed2000

Evidence for susceptibility genes to familial Wilms tumour in addition to WT1, FWT1 and FWT2.

Three loci have been implicated in familial Wilms tumour: WT1 located on chromosome 11p13, FWT1 on 17q12-q21, and FWT2 on 19q13. Two out of 19 Wilms tumour families evaluated showed strong evidence against linkage at all three loci. Both of these families contained at least three cases of Wilms tumour indicating that they were highly likely to be due to genetic susceptibility and therefore that one or more additional familial Wilms tumour susceptibility genes remain to be found.

Chromosomes, Human, Pair 11↗
PubMed1999

Genetic risk factors in colorectal cancer.

Familial risk factors are known to play an important role in colorectal cancer (CRC) risk, particularly when the relatives are affected by early-onset cancer. Part of this familial aggregation can be accounted for by inherited forms of colorectal cancer, i.e. familial adenomatous polyposis (less than 1% of all CRC) and hereditary nonpolyposis colorectal cancer (about 3%). Other genetic factors may be involved in the development of adenoma or in the transformation of adenoma into carcinoma. That the existence of polymorphisms of the adenomatous polyposis coli gene increase susceptibility to both adenomas and cancer favours this hypothesis. Interactions between environmental factors, and most of all dietary factors, and polymorphisms of carcinogen-metabolizing enzymes may also be involved. Better knowledge of these mechanisms will substantially widen the scope of colorectal cancer prevention.

Adenocarcinoma↗
PubMed1998

Marker segregation information in breast/ovarian cancer genetic counseling: is it still useful? Groupe Génétique et Cancer de la Fédération Nationale des Centres de Lutte Contre le Cancer.

The use of mutation screening of BRCA1 and BRCA2 genes as a genetic test is still to a certain extent limited and the oncogeneticist may want to use complementary approaches to identify at-risk individuals. In a series of 23 families with at least three breast or ovarian cancer cases, screened for mutations at BRCA1 and BRCA2 and typed for markers at both loci, we investigated the usefulness of marker segregation information at two levels: 1) to what extent can the indirect approach identify the mutation carrier status of screened cases and their first-degree relatives, and 2) in what way does it help to identify the gene implicated in a family in which neither BRCA1 nor BRCA2 mutation has been detected? Using the indirect approach, the carrier status of the screened case could be determined with quasi certainty in three families and with a high probability in eight families. This status could be inferred in unaffected first-degree relatives as almost certain in one family and as highly probable in six families. Fourteen mutations were found concurrently in our series. Among the nine mutation-negative families, we were able to conclude that a BRCA1 mutation most probably segregated in one and that a mutation other than BRCA1 and BRCA2 was probably involved in two families. Our results show that, in small families, little help is to be expected from linkage data and mutation screening is the only way of identifying the origin of a genetic predisposition in a family. Marker segregation information may be useful in some large breast/ovarian cancer families in which no BRCA1 or BRCA2 mutation has been detected.

BRCA1 Protein↗
PubMed1998

Segregation analysis in nonsyndromic holoprosencephaly.

Holoprosencephaly (HPE) is a developmental defect due to a failure of cleavage of the forebrain. The brain malformations are usually associated with facial anomalies. From a series of 258 HPE records involving at least one affected child, 97 cases in 79 families with nonsyndromic and nonchromosomal HPE were selected. The male:female ratio was 0.87. A high degree of familial aggregation was observed in 23/79 families (29%). A segregation analysis performed in the 79 nuclear families led to the conclusion that the transmission of nonsyndromic HPE is compatible with an autosomal dominant mode of inheritance. Under this hypothesis, the penetrance was estimated as 82% for major types (alobar, semilobar, lobar) and 88% when major and minor types (atypical) were included. The proportion of sporadic cases was estimated to be 68%. This genetic model allows a prediction of the recurrence risk after an isolated case of 13% for major types and 14% when minor types are included.

Diseases in Twins↗
PubMed1997

Radiation and genetic factors in the risk of second malignant neoplasms after a first cancer in childhood.

BACKGROUND: Radiotherapy and chemotherapy are associated with an increased risk of second malignant neoplasm (SMN). An association between SMN and familial aggregation has also been shown. The aim of this study was to investigate the role of familial factors in the risk of SMN and their potential interaction with the effect of treatment. METHODS: We devised a case-control study of 25 children with SMN (cases) and 96 children with no SMN after a cancer treatment (controls), taken from a cohort of 649 children treated at our institution between 1953 and 1985. A complete family history was obtained for patients and controls and a familial index defined to evaluate the degree of familial aggregation. The radiation dose given at 151 sites in the body was estimated for each radiotherapy course for each child. FINDINGS: Among family members of the 25 SMN cases, there were ten with early-onset (< or = 45 years) cancer, compared with eight among relatives of the 96 controls. Compared with patients who had no family history of early-onset cancer, those with one or more affected family members had an odds ratio for SMN of 4.7 (95% CI 1.3-17.1; p = 0.02). Adjustment for local radiation dose and exclusion of patients known to be predisposed to SMN (carriers of p53 mutation and those with Recklinghausen's disease) did not affect this risk substantially. INTERPRETATION: Both genetic factors and exposure to ionising radiation have independent effects on the risk of SMN. Follow-up of children treated for cancer should be especially vigilant when there is a family history of early-onset cancer.

Adolescent↗
PubMed1997

BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Institut Curie Breast Cancer Group.

An account of familial aggregation in breast/ovarian cancer has become possible with the identification of BRCA1 germ-line mutations. We evaluated, for 249 individuals registered with the Institut Curie in Paris, the prior probability that an individual carried a mutation that predisposes to these diseases. We chose 160 women for BRCA1 analysis: 103 with a family history of breast cancer and 57 with a family history of breast-ovarian cancer. To detect small mutations, we generated and analyzed 35 overlapping genomic PCR products that cover the coding portion of the gene, by using denaturing gradient gel electrophoresis. Thirty-eight truncating mutations (32 frameshifts, 4 nonsense mutations, and 2 splice variants) were observed in 15% of women with a family history of breast cancer only and in 40% of those with a history of breast-ovarian cancer. Twelve of 25 distinct truncating mutations identified were novel and unique. Most BRCA1 mutations that had been reported more than five times in the Breast Cancer Information Core were present in our series. One mutation (5149del4) observed in two apparently unrelated families most likely originates from a common ancestor. The position of truncating mutations did not significantly affect the ratio of the risk of breast cancer to that of ovarian cancer. In addition, 15 DNA variants (14 missense mutations and 1 neutral mutation) were identified, 9 of which were novel. Indirect evidence suggests that seven of these mutations are deleterious.

Africa↗