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: Cancer & Population. The organization has 2989 authors who have published 9010 publications receiving 929752 citations. The organization is also known as: IARC.

The viral origin of cervical cancer in Rabat, Morocco.

Abstract: In Northern Africa, cervical cancer is the second most common cancer among women. The diagnosis is usually made in advanced stages, and mortality is high, yet few studies have investigated the role of human papillomavirus (HPV) and other risk factors in the etiology of cervical cancer. A hospital-based case-control study was completed at the Institut National d'Oncologie (INO) in Rabat, Morocco. The study included 214 cases of invasive cervical cancer and 203 controls. A structured questionnaire was used to investigate known and suspected risk factors for cervical cancer. A GP 5+/6+ polymerase chain reaction system was used to detect the presence of HPV DNA and HPV type distribution. Probes for 30 HPV types were used in one research laboratory. HPV DNA was the central risk factor and accounted for the large majority of the cases. The adjusted odds ratio (ORa) for any HPV was 61.6 (95% CI, 29.2–130) and the corresponding HPV attributable fraction (AF) was 92%. Among cases of cervical cancer, HPV 16 was the most common type (67.7%) followed by HPV 18. The HPV type-specific prevalence was similar for squamous cell carcinomas and adenocarcinomas. In multivariate adjusted or HPV-stratified analyses, in addition to the strong effect of HPV, other risk factors identified were sexual intercourse with multiple partners before the age of 20 and low socio-economic status. Use of oral contraceptives for 5 or more years and high parity were also found to be related to cervical cancer. Screening was rare in this population but offered substantial protection against cervical cancer. In Morocco, cervical cancer is a late sequel of a viral infection with certain HPV types. Developing screening programs for preneoplastic cervical lesions is a public health priority. When available, HPV vaccination would offer a relevant alternative for preventing cervical cancer. Int. J. Cancer 75:546–554, 1998. © 1998 Wiley-Liss, Inc.

Regulation of p53 by metal ions and by antioxidants: dithiocarbamate down-regulates p53 DNA-binding activity by increasing the intracellular level of copper.

Abstract: Mutations in the p53 tumor suppressor gene frequently fall within the specific DNA-binding domain and prevent the molecule from transactivating normal targets. DNA-binding activity is regulated in vitro by metal ions and by redox conditions, but whether these factors also regulate p53 in vivo is unclear. To address this question, we have analyzed the effect of pyrrolidine dithiocarbamate (PDTC) on p53 DNA-binding activity in cell lines expressing wild-type p53. PDTC is commonly regarded as an antioxidant, but it can also bind and transport external copper ions into cells and thus exert either pro- or antioxidant effects in different situations. We report that PDTC, but not N-acetyl-L-cysteine, down-regulated the specific DNA-binding activity of p53. Loss of DNA binding correlated with disruption of the immunologically "wild-type" p53 conformation. Using different chelators to interfere with copper transport by PDTC, we found that bathocuproinedisulfonic acid (BCS), a non-cell-permeable chelator of Cu1+, prevented both copper import and p53 down-regulation. In contrast, 1,10-orthophenanthroline, a cell-permeable chelator of Cu2+, promoted the redox activity of copper and up-regulated p53 DNA-binding activity through a DNA damage-dependent pathway. We have previously reported that p53 protein binds copper in vitro in the form of Cu1+ (P. Hainaut, N. Rolley, M. Davies, and J. Milner, Oncogene 10:27-32, 1995). The data reported here indicate that intracellular levels and redox activity of copper are critical for p53 protein conformation and DNA-binding activity and suggest that copper ions may participate in the physiological control of p53 function.

Ovarian cancer and body size

Abstract: A reanalysis of published and unpublished data from epidemiological studies examines the association between height, body mass index, and the risk of developing ovarian cancer.

Prophylactic efficacy of a quadrivalent human papillomavirus (HPV) vaccine in women with virological evidence of HPV infection

Abstract: Background. A quadrivalent (types 6, 11, 16, and 18) human papillomavirus (HPV) L1 virus-like-particle (VLP) vaccine has been shown to be 95%-100% effective in preventing cervical and genital disease related to HPV-6,-11,-16, and-18 in 16-26-year-old women naive for HPV vaccine types. Because most women in the general population are sexually active, some will have already been infected with >= 1 HPV vaccine types at the time vaccination is offered. Here, we assessed whether such infected women are protected against disease caused by the remaining HPV vaccine types. Methods. Two randomized, placebo-controlled trials of the quadrivalent (types 6, 11, 16, and 18) HPV vaccine enrolled 17,622 women without consideration of baseline HPV status. Among women infected with 1-3 HPV vaccine types at enrollment, efficacy against genital disease related to the HPV vaccine type or types for which subjects were naive was assessed. Results. Vaccination was 100% effective (95% confidence interval [CI], 79%-100%) in preventing incident cervical intraepithelial neoplasia 2 or 3 or cervical adenocarcinoma in situ caused by the HPV type or types for which the women were negative at enrollment. Efficacy for preventing vulvar or vaginal HPV-related lesions was 94% (95% CI, 81%-99%). Conclusions. Among women positive for 1-3 HPV vaccine types before vaccination, the quadrivalent HPV vaccine protected against neoplasia caused by the remaining types. These results support vaccination of the general population without prescreening. (Less)

Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European Prospective Investigation into Cancer and Nutrition.

Abstract: Western style diets and lifestyles are associated with increasing rates of obesity, diabetes and insulin resistance. Higher circulating insulin levels may modulate cell proliferation and apoptosis either directly or indirectly by increasing the bioactivity of IGF-I and decreasing the bioactivity of some of its binding proteins. The objective of this study was to determine the association of increasing levels of serum C-peptide, a biomarker of pancreatic insulin secretion, and IGF binding proteins (IGFBP) -1 and -2 with colorectal cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 Western European countries. A total of 1,078 colorectal cancer cases were matched (age, date of blood donation, fasting status, gender, study center) to an equal number of control subjects. Relative cancer risks were estimated using conditional logistic regression models. Serum C-peptide concentration was positively associated with an increased colorectal cancer risk for the highest versus the lowest quintile (OR=1.56, 95% CI=1.16-2.09, p(trend)<0.01), which was slightly attenuated after adjustment for BMI and physical activity (OR=1.37, 95% CI=1.00-1.88, p(trend)=0.10). When stratified by anatomical site, the cancer risk was stronger in the colon (OR=1.67, 95% CI=1.14-2.46, p(trend)<0.01) than in the rectum (OR=1.42, 95% CI=0.90-2.25, p(trend)=0.35). The cancer risk estimates were not heterogeneous by gender or fasting status. No clear colorectal cancer risk associations were observed for IGFBP-1 or -2. This large prospective study confirms that hyperinsulinemia, as determined by C-peptide levels, is associated with an increased colorectal cancer risk.