IARC scientific publications最新文献

DNA, along with other cellular components, is under constant attack by chemical, physical, and infectious agents present in the human environment, as well as by reactive metabolites generated by physiological processes. Mutations occur as the consequence of this damage, but may also be caused by improper DNA repair of alterations occurring during normal DNA replication and transcription. Genetic damage can occur at the level of the gene (e.g. point mutations, insertions, and deletions) or at the level of the chromosome (e.g. aneuploidy, translocations). Further, mutations can also take place in mitochondrial DNA. Another form of DNA modification is epigenetic methylation of CpG islands, which affects the dynamics of chromatin as well as the expression of a large panel of genes. Recent technical advances have improved the capacity to detect and quantify genetic and epigenetic changes. This chapter summarizes current knowledge on mechanisms of DNA damage and mutagenesis, laying out the concepts for interpreting mutations as biomarkers in investigating the causes and consequences of cancer. It also outlines both established and novel methods for detecting genetic and epigenetic changes in normal and diseased tissues, and then discusses their application in the realm of molecular epidemiology.

The Izmir cancer registry, the first population-based cancer registry in Turkey, was established in 1992. Cancer registration is now done by active methods. The registry contributed data on survival for 12 cancer sites or types registered in 1995-1997. Follow-up was predominantly done by active methods with median follow-up ranging between 17-72 months for different cancers. The proportion with histologically verified diagnosis for various cancers ranged between 84-100%; there were no death certificate only (DCO) cases; 98-100% of total registered cases were included for the survival analysis. Complete follow-up at five years ranged from 79-98% for different cancers. Five-year age-standardized relative survival rates of common cancers were breast (77%), urinary bladder (70%), Larynx (69%), colon (53%), rectum (52%), non-Hodgkin Lymphoma (50%) and cervix (58%). Five-year relative survival by age group portrayed decreasing survival with increasing age at diagnosis for cancer of the cervix, and was fluctuating for other cancers. Decreasing survival with increasing clinical extent of disease was also noted.

The Kampala cancer registry was established in 1954 as a population-based cancer registry, and registration of cases is done by active methods. The registry contributed data on survival for 15 cancer sites or types registered in 1993-1997. For Kaposi sarcoma, only a random sample of the total incident cases was provided for survival study. Follow-up has been carried out predominantly by active methods, with median follow-up ranging from 4-26 months. The proportion with histologically verified diagnosis for various cancers ranged between 36-83%; death certificate only (DCO) cases were negligible; 58-92% of total registered cases were included for survival analysis. Complete follow-up at five years ranged between 47-87% for different cancers. Five-year age-standardized relative survival rates for selected cancers were Kaposi sarcoma (22%), cervix (19%), oesophagus (5%), non-Hodgkin lymphoma (26%), breast (36%) and prostate (46%). None survived beyond 5 years for cancers of the stomach and lung. Five-year relative survival by age group was fluctuating with no definite pattern or trend emerging and no survivors in many age intervals.

The rural cancer registry of Karunagappally was established in 1990 to study cancer occurrence due to high natural background radiation in the coastal area of Kerala state. Cancer registration was done by active methods. The registry contributed data on survival for 22 cancer sites or types registered during 1991-1997. Follow-up has been carried out predominantly by active methods, with median follow-up time ranging between 3-57 months for various cancers. The proportion of histologically verified diagnosis for different cancers ranged between 39-100%; death certificates only (DCOs) comprised 0-25%; 75-100% of total registered cases were included for survival analysis. The 5-year age-standardized relative survival rates for common cancers were lung (6%), breast (45%), cervix (55%), mouth (42%), oesophagus (14%) and tongue (31%). Five-year relative survival by age group showed no distinct pattern or trend for most cancers. A majority of cases are diagnosed with a regional spread of disease among cancers of the tongue (48%), oral cavity (66%), hypopharynx (54%), larynx (46%), cervix (61%) and breast (53%); survival decreases with increasing extent of disease.

The Karachi cancer registry established in 1995 was the first population-based cancer registry in Pakistan. Cancer registration is done by active methods. The registry contributed data on survival for selected cancers of the head and neck registered during 1995-1999. FoLlow-up has been carried out predominantly by active methods with the median follow-up time ranging between 29-36 months for different cancers. The proportion of histologically verified diagnosis for various cancers ranged between 98-100%; there were no cases as death certificates only (DCOs); 86-93% of total registered cases were included for survival analysis. Five-year followup ranged between 67-76%. The 5-year age-standardized relative survival rates was the highest for cancer of the salivary gland (44%), followed by oral cavity (40%), tongue (39%) and tonsil (3%). Five-year relative survival by age group did not display any pattern or trend and was fluctuating. A majority of cases have been diagnosed with a regional spread of disease: tongue (51%), oral cavity (53%), salivary gland (46%) and tonsil (79%) and survival decreased with increasing extent of disease for these cancers.

Family-based designs are used for a variety of reasons in genetic epidemiology, including the initial estimation of the strength of genetic effects for a disease, genetic linkage analysis by which genetic causes can be sublocalized to chromosomal regions, as well as to perform association studies that are not confounded by ethnic background. This chapter describes some of the approaches that are followed in the initial characterizing of genetic components of disease and family-based designs for association analysis and linkage with genetic markers.

The detection and characterization of microbial agents in biological specimens are essential for the investigation of disease outbreaks, for epidemiologic studies of the clinical course of infections, and for the assessment of the role of infectious agents in chronic diseases. Methodological approaches depend on the infectious agent, the specimens analysed and the target populations. Although the diagnosis of infectious diseases has traditionally relied on direct microscopic examination of samples and on the cultivation of microbial agents in vitro, novel techniques with increased sensitivity and specificity are now being used on samples that can be more easily collected and transported to microbiology laboratories (e.g. dried blood spots on filter paper for nucleic acid analysis). Direct detection techniques include the microscopic examination of specimens with special stains, antigen detection and nucleic acid detection by molecular assays. These assays are highly sensitive and provide rapid results for most agents. Genomic amplification assays greatly increase the sensitivity of nucleic acid-based tests by extensive amplification of specific nucleic acid sequences before detection. Real-time polymerase chain reaction (PCR) permits genomic amplification concurrently with detection of amplified products. Typing infectious agents requires additional investigation employing either serologic techniques to identify unique antigenic epitopes, or molecular techniques. These studies are important for epidemiologic purposes, as well as for the investigation of pathogenesis, disease progression, and to establish causality between a disease and a microbial agent. Much of bacteriology has relied on growth of organisms on artificial media, and on identification of bacterial growth with biochemical, serological, or more recently, nucleic acid-based tests. The detection of specific antibodies from the host directed against pathogens is another strategy to identify current or past infections.

This chapter focuses on biomarkers of reproductive health and disease that have been developed in the past 15 years. Due to the gender- and age-dependency of most of the advances in measuring reproductive health status and outcomes, these biomarkers have been categorized with respect to the unique member of the reproductive triad of interest (i.e. mother, father, conceptus). Biomarkers of female and male puberty, female reproductive function, fetal and infant development, and male reproductive function are discussed. The strengths and limitations of developing and implementing biomarkers in reproductive health studies over the past decade are explored.

The Lampang cancer registry was established in 1995, with retrospective data collection since 1988. Cancer registration is currently done by passive methods. The registry is contributing data on survival for 40 cancer sites or types registered during 1990-2000. Follow-up has been carried out by passive and active methods with median follow-up ranging from 1-74 months for different cancers. The proportion having a histologically verified diagnosis for various cancers ranged between 30-100%; death certificate only (DCO) cases comprised 0-33%; 67-100% of total registered cases were included for survival analysis. Complete follow-up at five years ranged from 96-100% for different cancers. The 5-year age-standardized relative survival rate was the highest for skin non-melanoma (85%) followed by lip (81%), thyroid (74%), corpus uteri (71%) and penis (71%). The 5-year relative survival by age group showed a fluctuating trend. An overwhelmingly high proportion of cases were diagnosed with a regional spread of disease, ranging from 35-68% for different cancers, and survival was decreasing with increasing extent of disease for most cancers studied.