Over the last two decades, ovarian cancer incidence and mortality for younger generations have been declining in most developed countries, and the decline has been greatest in countries where oral contraceptive (OC) use had spread earlier. The overall estimated protection from cohort and case-control studies is approximately 30% for ever OC users, and increases with duration of use by approximately 5% per year of use to about 50% for long-term (> or =10 years) users. The favourable effect of OC against ovarian cancer risk persists for at least 20 years after OC use has ceased, and it is not confined to any particular type of OC formulation. The reduced risk among OC users is observed in women without or with family history or genetic predisposition to ovarian cancer, and for most histological types of epithelial ovarian cancer, although the pattern of risk is less consistent for mucinous than for other types. The protection of OC on ovarian cancer risk, also in view of its long-term persistence, corresponds to the avoidance of 3000-5000 ovarian cancers (and 2000-3000 deaths) per year in Europe, and a similar figure in North America.
Pregnancy-associated cancers are malignancies diagnosed during pregnancy or within one year of delivery or abortion. These cancers present unique challenges because of the delicate balance required for maternal-fetal health. Diagnosis can be made complex by physiological changes associated with pregnancy, and treatment decisions must take into account potential harm to the foetus. Multidisciplinary collaboration between oncologists and obstetricians is essential. Despite the complexities, early detection and tailored management can optimise outcomes for both mother and child. A systematic approach is currently lacking; further research into prenatal exposure to maternal cancer is recommended to formulate evidence-based guidelines for the management of cancer in pregnancy.
1Istituto di Ricerche Farmacologiche “Mario Negri”, 20157 Milano and Istituto di Statistica Medica e Biometria, Università degli Studi di Milano, 20133 Milano, Italy 2International Agency for Research on Cancer, 69372 Lyon Cedex, France Fax: (+39) 02 3320 0231; E-mail: [email protected]
This meta-analysis estimates the excess of esophageal and gastric cardia adenocarcinoma risk for smokers. This risk was similar for the 2 cancer sites.
Insulin-like growth factor-binding protein-2 (IGF-BP-2) transcription in rat liver varies with developmental age and fasting. To define the DNA elements required for efficient expression of the TATA-less rat IGFBP-2 gene, the native or mutated promoter was fused to a promoterless luciferase reporter gene and transfected into BRL-3A rat liver and 293 human embryonic kidney cell lines. Luciferase activity decreased approximately 25-fold with progressive 5' promoter deletions from nucleotide (nt) −581 to nt −189 (relative to ATG, +1). The smallest construct, however, still had > 21-fold greater luciferase activity than the promoterless construct. In DNase I foot-printing assays using native nt −276 to −36 promoter fragments or fragments containing block substitution mutations, BRL-3A nuclear extract and purified human transcription factor Sp1 protected a region from nt −234 to −215 containing one GC box and a broad region from nt −189 to −125 that contained three clustered but independent GC boxes. In gel retardation assays using an Sp1 oligonucleotide probe, BRL-3A extract formed two closely migrating complexes that were immunologically related to Sp1; Sp1 gave a single complex that co-migrated with the more retarded BRL-3A complex. Binding was competitively inhibited by oligonucleotides corresponding to each of the four GC boxes. The proximal three GC boxes were sufficient to allow trans-activation of the IGFBP-2 promoter by Sp1 in Drosophila SL2 cells. Independent block mutations indicated that all three of the GC boxes are required for promoter activity and are equally important. Thus, binding of Sp1 or Sp1-related proteins to three clustered GC boxes in the proximal IGFBP-2 promoter is essential for promoter activity. Multiple upstream regions also contribute to the full expression of the IGFBP-2 gene.
