International Agency for Research on Cancer

About: International Agency for Research on Cancer is a government organization based out in Lyon, France. It is known for research contribution in the topics: Population & Cancer. The organization has 2989 authors who have published 9010 publications receiving 929752 citations. The organization is also known as: IARC.

Metalloregulation of the tumor suppressor protein p53: zinc mediates the renaturation of p53 after exposure to metal chelators in vitro and in intact cells.

Abstract: The tumor suppressor p53 is a transcription factor which binds DNA through a structurally complex domain stabilized by a zinc atom. Zinc chelation disrupts the architecture of this domain, inducing the protein to adopt an immunological phenotype identical to that of many mutant forms of p53. In this report, we used 65Zn to show that incorporation of zinc within the protein was required for folding in the 'wild-type' conformation capable of specific DNA-binding. Using a cellular assay, we show that addition of extracellular zinc at concentrations within the physiological range (5 microM) was required for renaturation and reactivation of wild-type p53. Among other divalent metals tested (Cd2+, Cu2+, Co2+, Fe2+ and Ni2+), only Co2+ at 125 microM had a similar effect. Recombinant metallothionein (MT), a metal chelator protein, was found to modulate p53 conformation in vitro. In cultured cells, overexpression of MT by transfection could modulate p53 transcriptional activity. Taken together, these results suggest that zinc binding plays a regulatory role in the control of p53 folding and DNA-binding activity.

Male sexual behavior and human papillomavirus DNA: key risk factors for cervical cancer in Spain.

Abstract: Background: It is now established that certain types of human papillomaviruses (HPVs) are the sexually transmitted agents etiologically linked to cervical cancer. Studies assessing the contribution of the male's sexual behavior and genital HPV DNA status to the risk of development of cervical neoplasia in sexual partners have yielded inconsistent results. Purpose: This study evaluates the role of men's sexual behavior and the presence of HPV DNA in the penis on the development of cervical cancer in their sexual partners in Spain, a low-risk area for cervical neoplasia. Methods: Husbands (n = 633) of women participating in two case-control studies of cervical neoplasia were interviewed to obtain information on lifestyle habits, including sexual practices. Cytologic samples were taken from the distal urethra and the surface of the glans penis of 183 husbands of case women and of 171 husbands of control women. These samples were analyzed by a polymerase chain reaction-based system using a generic probe and 25 type-specific probes for the detection and typing of HPV DNA. Serologic specimens were also obtained and analyzed for antibodies to Chlamydia trachomatis, Treponema pallidum, herpes simplex virus type II, and Neisseria gonorrhoeae. Results: The presence of HPV DNA in the husbands' penis conveyed a fivefold risk of cervical cancer to their wives (adjusted odds ratio [OR] for HPV DNA positivity = 4.9; 95% confidence interval [CI] = 1.9-12.6). The risk of cervical cancer was strongly related to HPV type (adjusted OR for HPV type 16 = 9.0; 95% CI = 1.1-77.5), to the husbands' number of extramarital partners (adjusted OR = 11.0; 95% CI = 3.0-40.0; for >21 women versus one), and to the number of prostitutes as extramarital sexual partners (adjusted OR = 8.0; 95% CI = 2.9-22.2; for £10 women versus none). Presence of antibodies to C. trachomatis (adjusted OR = 2.6; 95% CI = 1.4-4.6) and an early age at first sexual intercourse of the husband (adjusted OR = 3.2; 95% CI = 1.7-5.9; for ^15 years versus £21 years) were also associated with cervical neoplasia in the wife. After adjustment for these variables and for the wife's pack-years of smoking, the husband's smoking was moderately associated with cervical cancer in his wife (adjusted OR = 2.5; 95% CI = 1.4-4.4; for >26.2 pack-years versus none). Conclusions: The study supports the role of men as vectors of the HPV types that are related to cervical cancer. Lifetime number of female sexual partners, number of female prostitutes as sexual partners, and detection of HPV DNA in the penis of husbands are all surrogate markers of exposure to HPV during marriage. Implications: Men who report multiple sexual partners or who are carriers of HPV DNA may be vectors of high-risk HPV types and may place their wives at high risk of developing cervical cancer. Prostitutes are an important reservoir of high-risk HPVs. [J Natl Cancer Inst 1996;88:1060-7]

Colorectal cancer and diet in an asian population—A case-control study among Singapore Chinese

Abstract: A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.

Classification of rare missense substitutions, using risk surfaces, with genetic- and molecular-epidemiology applications.

Abstract: Many individually rare missense substitutions are encountered during deep resequencing of candidate susceptibility genes and clinical mutation screening of known susceptibility genes BRCA1 and BRCA2 are among the most resequenced of all genes, and clinical mutation screening of these genes provides an extensive data set for analysis of rare missense substitutions Align-GVGD is a mathematically simple missense substitution analysis algorithm, based on the Grantham difference, which has already contributed to classification of missense substitutions in BRCA1, BRCA2, and CHEK2 However, the distribution of genetic risk as a function of Align-GVGD's output variables Grantham variation (GV) and Grantham deviation (GD) has not been well characterized Here, we used data from the Myriad Genetic Laboratories database of nearly 70,000 full-sequence tests plus two risk estimates, one approximating the odds ratio and the other reflecting strength of selection, to display the distribution of risk in the GV-GD plane as a series of surfaces We abstracted contours from the surfaces and used the contours to define a sequence of missense substitution grades ordered from greatest risk to least risk The grades were validated internally using a third, personal and family history-based, measure of risk The Align-GVGD grades defined here are applicable to both the genetic epidemiology problem of classifying rare missense substitutions observed in known susceptibility genes and the molecular epidemiology problem of analyzing rare missense substitutions observed during case-control mutation screening studies of candidate susceptibility genes

Physical Activity and Risk of Colon and Rectal Cancers: The European Prospective Investigation into Cancer and Nutrition

Abstract: We investigated several aspects of the role of physical activity in colon and rectal cancer etiology that remain unclear in the European Prospective Investigation into Nutrition and Cancer. This cohort of 413,044 men and women had 1,094 cases of colon and 599 cases of rectal cancer diagnosed during an average of 6.4 years of follow-up. We analyzed baseline data on occupational, household, and recreational activity to examine associations by type of activity, tumor subsite, body mass index (BMI), and energy intake. The multivariate hazard ratio for colon cancer was 0.78 [95% confidence interval (95% CI), 0.59-1.03] among the most active participants when compared with the inactive, with evidence of a dose-response effect (P(trend) = 0.04). For right-sided colon tumors, the risk was 0.65 (95% CI, 0.43-1.00) in the highest quartile of activity with evidence of a linear trend (P(trend) = 0.004). Active participants with a BMI under 25 had a risk of 0.63 (95% CI, 0.39-1.01) for colon cancer compared with the inactive. Finally, an interaction between BMI and activity (P(interaction) = 0.03) was observed for right-sided colon cancers; among moderately active and active participants with a BMI under 25, a risk of 0.38 (95% CI, 0.21-0.68) was found as compared with inactive participants with BMI >30. No comparable decreased risks were observed for rectal cancer for any type of physical activity for any subgroup analyses or interactions considered. We found that physical activity reduced colon cancer risk, specifically for right-sided tumors and for lean participants, but not rectal cancer.