Bulletin Du Cancer 

About: Bulletin Du Cancer is an academic journal published by Elsevier BV. The journal publishes majorly in the area(s): Cancer & Medicine. It has an ISSN identifier of 0007-4551. Over the lifetime, 6196 publications have been published receiving 37578 citations.

Cancer risks associated with germline mutations in MLH1, MSH2 and MSH6 genes in Lynch syndrome: results from the large nationwide French ERISCAM study

Abstract: CONTEXT Providing accurate estimates of cancer risks is a major challenge in the clinical management of Lynch syndrome. OBJECTIVE To estimate the age-specific cumulative risks of developing various tumors using a large series of families with mutations of the MLH1, MSH2, and MSH6 genes. DESIGN, SETTING, AND PARTICIPANTS Families with Lynch syndrome enrolled between January 1, 2006, and December 31, 2009, from 40 French cancer genetics clinics participating in the ERISCAM (Estimation des Risques de Cancer chez les porteurs de mutation des gènes MMR) study; 537 families with segregating mutated genes (248 with MLH1; 256 with MSH2; and 33 with MSH6) were analyzed. MAIN OUTCOME MEASURE Age-specific cumulative cancer risks estimated using the genotype restricted likelihood (GRL) method accounting for ascertainment bias. RESULTS Significant differences in estimated cumulative cancer risk were found between the 3 mutated genes (P = .01). The estimated cumulative risks of colorectal cancer by age 70 years were 41% (95% confidence intervals [CI], 25%-70%) for MLH1 mutation carriers, 48% (95% CI, 30%-77%) for MSH2, and 12% (95% CI, 8%-22%) for MSH6. For endometrial cancer, corresponding risks were 54% (95% CI, 20%-80%), 21% (95% CI, 8%-77%), and 16% (95% CI, 8%-32%). For ovarian cancer, they were 20% (95% CI, 1%-65%), 24% (95% CI, 3%-52%), and 1% (95% CI, 0%-3%). The estimated cumulative risks by age 40 years did not exceed 2% (95% CI, 0%-7%) for endometrial cancer nor 1% (95% CI, 0%-3%) for ovarian cancer, irrespective of the gene. The estimated lifetime risks for other tumor types did not exceed 3% with any of the gene mutations. CONCLUSIONS MSH6 mutations are associated with markedly lower cancer risks than MLH1 or MSH2 mutations. Lifetime ovarian and endometrial cancer risks associated with MLH1 or MSH2 mutations were high but do not increase appreciably until after the age of 40 years.

Population study of dihydropyrimidine dehydrogenase in cancer patients

Abstract: La dihydropyrimidine deshydrogenase (DPD) est l'enzyme initiale cle du catabolisme du 5-fluorouracile (5-FU). L'importance clinique de la DPD a ete recemment mise en evidence par l'identification de patients presentant un deficit en DPD decele dans les lymphocytes et qui avaient developpe des toxicites severes, voire letales, au 5-FU. Nous avons mene une etude prospective afin d'analyser la distribution de l'activite DPD lymphocytaire sur une population consequente de sujets cancereux. La population exploree comprenait 185 patients (152 hommes d'âge moyen 62,1 et 33 femmes d'âge moyen 59,2). Soixante-huit etaient des patients ORL traites par 5-FU (perfusion continue sur 5 jours, dose initiale 1g/m 2 /j avec adaptation posologique a mi-cycle) pour lesquels l'activite DPD etait mesuree 2-3 jours avant l'administration du 5-FU (94 cycles analyses). L'activite DPD etait mesuree par une methode radioenzymatique utilisant du 14 C-5-FU. La distribution de l'activite DPD etait unimodale et pouvait etre assimilee a une loi normale. Les valeurs moyennes et medianes etaient respectivement de 0,222 et 0,211 nmol/min/mg prot (extremes : 0,065-0,559). Aucun deficit total n'etait observe. Ni la fonction hepatique, ni l'âge n'influencaient l'activite DPD ; en revanche l'activite DPD etait en moyenne 15% plus faible chez la femme que chez l'homme (respectivement 0,194 et 0,228 nmol/min/mg prot, p = 0,03). Chez les patients traites par 5-FU, la survenue d'une toxicite n'etait pas liee a l'activite DPD mesuree avant traitement mais etait liee a l'exposition systemique au 5-FU. La correlation entre l'activite DPD lymphocytaire et la clairance au 5-FU etait faible (n = 90, r = 0,31, p = 0,002). En corollaire, l'activite DPD chez les patients necessitant une reduction de dose n'etait pas significativement differente de celle des patients ne necessitant pas de modification de dose. En conclusion, les deficits totaux en DPD semblent etre des evenements tres rares. Bien que la mesure de l'activite DPD ne permette pas d'ameliorer la strategie d'adaptation posologique, l'identification de deficits partiels (< 0,100 nmol/min/mg prot, 3% de la population) pourrait conduire a reduire la dose de 5-FU d'emblee.

New guidelines to evaluate the response to treatment in solid tumors

Abstract: Anticancer agents go through a process by which their antitumor activity, on the basis of the amount of tumor shrinkage they could generate, has been investigated. In the late 1970s, the International Union Against Cancer and the World Health Organization (WHO) introduced specific criteria for the codification of tumor response evaluation. In 1994, several organizations involved in clinical cancer research joined together to undertake the review of these response evaluation criteria on the basis of their experience and knowledge. After several years of intensive discussions, new guidelines are ready and will replace the previous WHO criteria. In parallel to this initiative, one of the participating groups developed a model by which response rates could be derived from unidimensional measurement of tumor lesions instead of the usual bidimensional approach. This new concept has been largely validated by the Response Evaluation Criteria in Solid Tumors (Recist) Group and integrated into the present guidelines. This special article provides some philosophic background to clarify the various purposes of response evaluation. It proposes a model by which a combined assessment of all existing lesions, characterized by target lesion (to be measured) and nontarget lesions, is used to extrapolate an overall response to treatment. Methods of assessing tumor lesions are better codified. All other aspects of response evaluation have been discussed, reviewed, and amended whenever suitable.

Primary prevention of colorectal cancer

Abstract: Results from case-control studies and prospective studies suggest that diet is involved in the causation of large bowel cancer either as initiator, promoter or inhibitor of carcinogenesis. Available data are not sufficient to serve as a basis for firm specific dietary advice. In the present situation it is attractive to investigate available hypotheses within the frame work of intervention trials. The adenoma appears to be one of the most appropriate end point of intervention studies. Several arguments indicate that the adenoma-carcinoma sequence is a multistep process. Colorectal cancer could possibly be prevented by intervening in the development of a small adenoma or in the growth into a large adenoma. Four intervention trials have been published so far. One of them suggest a protective effect of antioxidants vitamins on adenoma recurrence and three of them conclude to the absence of effect of these vitamins. A protective effect of lactulose on adenoma recurrence has also been suggested. Three studies are currently evaluating the effect of calcium supplementation on adenoma recurrence or growth of calcium supplementation, three studies the effect of fibre supplements, two studies the effect of antioxidants (one of them with calcium) and two studies the effect of diet intervention. The results of these studies will be available within three years.

[Esophageal cancer in Ille-et-Vilaine in relation to levels of alcohol and tobacco consumption. Risks are multiplying].

Abstract: A retrospective case-control study of 200 male cases of oesophageal cancer and 778 population controls has been carried out in Ille-et-Vilanine (France). The logarithms of the relative risks of developing the disease increase linearly with daily consumption of alcohol and tobacco independently. The combined effect of both fit with a multiplicative model which is proposed. This model could be applicable to other situations. It explains the sex ratio and the urban/rural differences observed in Ille-er-Vilaine. The practical implications for public health purposes are briefly discussed.