Showing papers by "International Agency for Research on Cancer published in 2004"

Genetic pathways to glioblastoma: a population-based study.

Abstract: We conducted a population-based study on glioblastomas in the Canton of Zurich, Switzerland (population, 1.16 million) to determine the frequency of major genetic alterations and their effect on patient survival. Between 1980 and 1994, 715 glioblastomas were diagnosed. The incidence rate per 100,000 population/year, adjusted to the World Standard Population, was 3.32 in males and 2.24 in females. Observed survival rates were 42.4% at 6 months, 17.7% at 1 year, and 3.3% at 2 years. For all of the age groups, younger patients survived significantly longer, ranging from a median of 8.8 months ( 80 years). Loss of heterozygosity (LOH) 10q was the most frequent genetic alteration (69%), followed by EGFR amplification (34%), TP53 mutations (31%), p16(INK4a) deletion (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the other genetic alterations and was predictive of shorter survival. Primary (de novo) glioblastomas prevailed (95%), whereas secondary glioblastomas that progressed from low-grade or anaplastic gliomas were rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hotspot codons 248 and 273, whereas in primary glioblastomas, mutations were more equally distributed. G:C-->A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas (56% versus 30%; P = 0.0208). This suggests that the acquisition of TP53 mutations in these glioblastoma subtypes occurs through different mechanisms.

Against which human papillomavirus types shall we vaccinate and screen? The international perspective.

Abstract: At least 15 types of HPV have been associated with cervical cancer, but current HPV vaccines confer only type-specific immunity. To determine geographic variations in the HPV type distribution in cervical cancer, we carried out a pooled analysis of data from an international survey of HPV types in cervical cancer and from a multicenter case-control study, both co-coordinated by the IARC. Study cases were 3,607 women with incident, histologically confirmed cervical cancer recruited in 25 countries. HPV DNA detection and typing in cervical cells or biopsies were centrally done using PCR assays. Estimates of the potential number of cases prevented by HPV type-specific vaccines and changes in the validity of different HPV screening cocktails were calculated. HPV DNA was detected in 96% of specimens, and 30 different types were detected. The 15 most common types were, in descending order of frequency, 16, 18, 45, 31, 33, 52, 58, 35, 59, 56, 39, 51, 73, 68 and 66. Higher than average proportions of type 16 were found in northern Africa, of type 18 in south Asia, of type 45 in sub-Saharan Africa and of type 31 in Central/South America. A vaccine including types 16 and 18 could potentially prevent 71% of cervical cancers worldwide, but its impact with regard to the percentage of cases potentially prevented would be higher in Asia and Europe/North America. In contrast, a vaccine containing the 7 most common HPV types would prevent about 87% of cervical cancers worldwide, with little regional variation. The impact of modifying the number of types in the screening cocktail tests would be small and probably irrelevant for screening programs.

The changing global patterns of female breast cancer incidence and mortality

Abstract: One in ten of all new cancers diagnosed worldwide each year is a cancer of the female breast, and it is the most common cancer in women in both developing and developed areas. It is also the principal cause of death from cancer among women globally. We review the descriptive epidemiology of the disease, focusing on some of the key elements of the geographical and temporal variations in incidence and mortality in each world region. The observations are discussed in the context of the numerous aetiological factors, as well as the impact of screening and advances in treatment and disease management in high-resource settings.

Tobacco and cancer: recent epidemiological evidence.

Abstract: During the 1950s, the evidence was clearly sufficient to establish the carcinogenicity of tobacco smoking (1). By the end of the 1950s, convincing evidence linking smoking with lung cancer and other cancers had been obtained from case–control and cohort studies, carcinogens had been identified in tobacco smoke, and cigarette smoke condensate had been shown to cause tumors when painted on the skin of mice. Since then, the numbers of deaths attributable to tobacco smoking have sharply increased, reflecting the heavy smoking patterns of previous decades. It has been estimated that tobacco smoking is currently responsible for approximately 30% of all cancer deaths in developed countries, and that if current smoking patterns persist, an epidemic of cancer attributable to tobacco smoking is expected to occur in developing countries (2). In addition, smoking causes even more deaths from vascular, respiratory, and other diseases than from cancer, so that, in total, tobacco smoking is estimated to account for approximately 4–5 million deaths a year worldwide. This number is projected to increase to approximately 10 million a year by 2030. Thus, if current smoking patterns continue, there will be more than 1 billion deaths attributable to tobacco smoking in the 21 century compared with approximately 100 million deaths in the 20 century (2). The only other causes of disease with such rapidly increasing impact are those associated with human immunodeficiency virus infection and, perhaps, obesity in Western countries (2). In this commentary, we review the evidence regarding the carcinogenicity of tobacco smoke that has accumulated during the last 16 years since the publication of Monograph 38 of the International Agency for Research on Cancer (IARC) in 1986 (3) to the updating of that monograph (Monograph 83) in 2002 (4). The evidence now available shows that tobacco smoke is a multipotent carcinogenic mixture that can cause cancer in many different organs. In addition, exposure to secondhand tobacco smoke (i.e., involuntary or passive smoking by persons who do not smoke) is also carcinogenic for the human lung. This commentary, written by the epidemiologists who participated in the 2002 IARC Working Group for the preparation of the IARC Monograph 83 (4), is based on the substantial body of evidence reviewed for that purpose. It represents, however, solely the views of the authors.

Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC).

Abstract: The evidence for anthropometric factors influencing breast cancer risk is accumulating, but uncertainties remain concerning the role of fat distribution and potential effect modifiers. We used data from 73,542 premenopausal and 103,344 postmenopausal women from 9 European countries, taking part in the EPIC study. RRs from Cox regression models were calculated, using measured height, weight, BMI and waist and hip circumferences; categorized by cohort-wide quintiles; and expressed as continuous variables, adjusted for study center, age and other risk factors. During 4.7 years of follow-up, 1,879 incident invasive breast cancers were identified. In postmenopausal women, current HRT modified the body size-breast cancer association. Among nonusers, weight, BMI and hip circumference were positively associated with breast cancer risk (all ptrend 30) had a 31% excess risk compared to women with BMI < 25. Among HRT users, body measures were inversely but nonsignificantly associated with breast cancer. Excess breast cancer risk with HRT was particularly evident among lean women. Pooled RRs per height increment of 5 cm were 1.05 (95% CI 1.00-1.16) in premenopausal and 1.10 (95% CI 1.05-1.16) in postmenopausal women. Among premenopausal women, hip circumference was the only other measure significantly related to breast cancer (ptrend = 0.03), after accounting for BMI. In postmenopausal women not taking exogenous hormones, general obesity is a significant predictor of breast cancer, while abdominal fat assessed as waist-hip ratio or waist circumference was not related to excess risk when adjusted for BMI. Among premenopausal women, weight and BMI showed nonsignificant inverse associations with breast cancer.

Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2.

Abstract: Many sequence variants in predisposition genes are of uncertain clinical significance, and classification of these variants into high- or low-risk categories is an important problem in clinical genetics. Classification of such variants can be performed by direct epidemiological observations, including cosegregation with disease in families and degree of family history of the disease, or by indirect measures, including amino acid conservation, severity of amino acid change, and evidence from functional assays. In this study, we have developed an approach to the synthesis of such evidence in a multifactorial likelihood-ratio model. We applied this model to the analysis of three unclassified variants in BRCA1 and three in BRCA2. The evidence strongly suggests that two variants (C1787S in BRCA1 and D2723H in BRCA2) are deleterious, three (R841W in BRCA1 and Y42C and P655R in BRCA2) are neutral, and one (R1699Q in BRCA1) remains of uncertain significance. These results provide a demonstration of the utility of the model.

Diet and cancer — the European Prospective Investigation into Cancer and Nutrition

Abstract: Diet is thought to be one of the most important contributing factors to cancer risk. The contribution of diet to cancer is linked to genetic factors, and uncovering the details of this linkage requires that very large studies be carried out over long time periods, with a detailed analysis of food intake. For this reason, the European Prospective Investigation into Cancer and Nutrition — a study of over 500,000 people in 10 European countries — was devised, to investigate the relationship between diet, metabolic and genetic factors, and cancer. How will this study be run, and will it be able to avoid some of the problems of measurement error that were previously encountered with other dietary studies?

Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas

Abstract: We carried out a population-based study on low-grade diffuse gliomas in the Canton of Zurich, Switzerland (population 1.16 million). From 1980 to 1994, 987 astrocytic and oligodendroglial tumors were diagnosed, of which 122 (12.4%) were low-grade (WHO grade II). The incidence rates adjusted to the World Standard Population, per million population per year, were 2.28 for low-grade diffuse astrocytomas, 0.89 for oligoastrocytomas, and 2.45 for oligodendrogliomas. The survival rate (mean follow-up 7.5+/-4.8 years) was highest for patients with oligodendroglioma (78% at 5 years, 51% at 10 years), followed by those with oligoastrocytoma (70% at 5 years, 49% at 10 years) and fibrillary astrocytoma (65% at 5 years, 31% at 10 years). Survival of patients with gemistocytic astrocytoma was poor, with survival rates of 16% at 5 years and 0% at 10 years. Younger patients ( 50 years; P=0.013). DNA sequencing, performed in 84% of cases, revealed that TP53 mutations were most frequent in gemistocytic astrocytomas (88%), followed by fibrillary astrocytomas (53%) and oligoastrocytomas (44%), but were infrequent (13%) in oligodendrogliomas. The presence of TP53 mutations was associated with shorter survival of patients with low-grade diffuse gliomas (log-rank test; P=0.047), but when each histological type was analyzed separately, an association was observed only for oligoastrocytoma ( P=0.05). Loss on 1p and 19q were assessed by quantitative microsatellite analysis in 67% of cases. These alterations were frequent in oligodendrogliomas (1p, 57%; 19q, 69%), less common in oligoastrocytomas (1p, 27%; 19q, 45%), rare in fibrillary astrocytomas (1p, 7%; 19q, 7%), and absent in gemistocytic astrocytomas. None of these alterations were predictive of survival. These results establish the frequency of key genetic alterations in low-grade diffuse gliomas at a population-based level. Multivariate Cox's regression analysis indicates that only age and histological type, but not genetic alterations, are significant predictive factors.

Obesity and colon cancer: Does leptin provide a link?

Abstract: Obesity, a risk factor for colorectal cancer, is associated with elevated serum levels of leptin, the adipocyte-derived hormone, and insulin. Experimental and epidemiologic studies have indicated a role for insulin in the pathogenesis of colon cancer, and recent experimental studies have suggested a similar role for leptin. In a case-control study nested in the Janus Biobank, Norway, we measured serum levels of leptin and C-peptide (a marker of pancreatic insulin secretion) in cryopreserved prediagnostic sera from men (median age, 45 years) who were diagnosed with cancer of the colon (n = 235) or rectum (n = 143) after blood collection (median time, 17 years), and among 378 controls matched for age and date of blood collection. Conditional logistic regression analyses showed an approximately 3-fold increase in colon cancer risk with increasing concentrations of leptin up to an odds ratio (OR) of 2.72 (95% CI = 1.44-5.12) for top vs. bottom quartile (p(trend) = 0.008). The corresponding OR for C-peptide was 1.81 (95% CI = 0.67-4.86; p(trend) = 0.19). The risk estimates remained unchanged after mutual adjustment. No association of hormone levels with rectal cancer risk was found. Reproducibility of hormone measurements assessed by intraclass coefficients (ICCs) for paired samples taken 1 year apart was high for leptin (ICC = 0.82) but lower for C-peptide (ICC = 0.30). Our results suggest that leptin is a risk factor for colon cancer, and that leptin may provide a link between obesity and colon cancer. Leptin may be directly involved in colon tumorigenesis or it may serve as a sensitive and robust marker of an obesity-induced adverse endocrine environment. Only weak support for an association of insulin with colon cancer was found.

Accuracy of visual screening for cervical neoplasia: Results from an IARC multicentre study in India and Africa.

Abstract: Visual inspection-based screening tests, such as visual inspection with 4% acetic acid (VIA) and with Lugol's iodine (VILI), have been proposed as alternatives to cytology in mass screening programs. To date, there is only limited information on the accuracy of these tests in detecting High-grade Squamous Intraepithelial Lesions (HSIL). Eleven cross-sectional studies involving 56,939 women aged 25-65 years were conducted in Burkina Faso, Congo, Guinea, India, Mali and Niger to evaluate the accuracy of VIA and VILI performed by health workers. A common protocol and questionnaire was used. For final diagnosis, all women were investigated with colposcopy and biopsies were taken when necessary. Data from the studies were pooled to calculate sensitivity, specificity and predictive values of the tests for the detection of HSIL. Of the screened women, 16.1% and 16.4% were positive on examination using, respectively, VIA and VILI; 1,063 were diagnosed with HSIL. The pooled sensitivity, specificity, positive and negative predictive values for VIA were 76.8% (95% CI: 74.2-79.4%), 85.5% (95% CI: 85.2-85.8%), 9.4% (95% CI:8.8-10.8%) and 99.5% (95% CI:99.4-99.6%), respectively. The values were 91.7% (95% CI: 89.7-93.4%), 85.4% (95% CI: 85.1-85.7%), 10.9% (95% CI: 10.2-11.6%) and 99.8% (95% CI:99.7-99.9%), respectively for VILI. The range of sensitivity and specificity for VIA was 56.1-93.9% and 74.2-93.8%, respectively, between studies and were 76.0-97.0 % and 73.0-91.3% for VILI. VILI had a significantly higher sensitivity than VIA in detecting HSIL, but specificity was similar. VILI appears to be a more accurate visual test for use in screening and treatment programs in low-resource settings.

Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women.

Abstract: OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IG ...

Chlamydia trachomatis and invasive cervical cancer: a pooled analysis of the IARC multicentric case-control study

Abstract: To determine whether Chlamydia trachomatis infection is consistently associated with an increased risk of invasive cervical carcinoma (ICC) after accounting for the strong effect of human papillomavirus (HPV) infection, a case-control study of 1,238 cases of ICC and 1,100 control women from 7 countries was carried out (hospital-based studies in Thailand, the Philippines, Morocco, Peru, Brazil and population-based studies in Colombia and Spain, all coordinated by the International Agency for Research on Cancer, Lyon, France). C. trachomatis serum antibody detection was made by means of a microfluorescence assay. Among HPV DNA-positive cases and controls, the risk of squamous cell ICC was elevated in C. trachomatis seropositive women (OR = 1.8; 95% CI = 1.2-2.7) after adjustment for age, center, oral contraceptive use, history of Pap smears, number of full-term pregnancies and herpes simplex virus 2 seropositivity. The effect of C. trachomatis seropositivity on squamous cell ICC risk increased with increasing C. trachomatis antibody titers and was higher in women under 55 years of age. C. trachomatis antibodies were not associated with adeno- or adenosquamous cell carcinoma (OR = 1.0; 95% CI = 0.53-1.9) in HPV DNA-positive women. An association of C. trachomatis with squamous cell ICC was found among all cases and control women with or without adjustment for HPV.

The role of type of tobacco and type of alcoholic beverage in oral carcinogenesis.

Abstract: Incidence rates of oral and oropharyngeal cancers (oral cancer) in Spain are among the highest in Europe. Spain has a population heavily exposed to various types of tobacco and alcoholic beverages but the role and impact of tobacco type and beverage type in oral carcinogenesis remain controversial. To estimate the independent and joint effects of tobacco smoking and alcohol drinking habits on the risk of developing oral cancer, we carried out a multicenter, hospital-based, case-control study in Spain. Data from 375 patients newly diagnosed with cancer of the oral cavity or oropharynx and 375 matched control subjects were analyzed using multivariate logistic regression procedures. All exposure characteristics of amount, duration and cessation of both tobacco smoking and alcohol drinking were strongly associated with cancer risk following a dose-dependent relationship. At equal intake or duration levels, black-tobacco smoking and drinking of spirits were both associated with a 2- to 4-fold increase in cancer risk compared to blond tobacco smoking or drinking of wine or beer, respectively. While ever exposure to smoking only or drinking only was associated with a moderate and nonsignificant increase in cancer risk, a history of simultaneous exposure to both habits was associated with a 13-fold increase that was compatible with a synergistic effect model (p-value for interaction: 0.008). Exposure to black tobacco smoking and/or drinking of spirits may account for up to 77% of oral cancer occurrence in Spain. Both black tobacco smoking and drinking of spirits place individuals at a very high risk of developing oral cancer. Simultaneous exposure to tobacco and alcohol consumption increases oral cancer risk in a synergistic fashion, even when consumption levels are moderate. These results underline the importance of type of tobacco and alcohol concentration in oral carcinogenesis.

Circulating adiponectin and endometrial cancer risk.

Abstract: Circulating levels of adiponectin, a hormone with insulin-sensitizing properties, are decreased in conditions related to obesity and hyperinsulinemia, which are recognized risk factors for endometrial cancer. Eighty-seven cases with incident, histologically confirmed endometrial cancer and 132 controls admitted for acute, nonneoplastic diseases were interviewed in northeastern Italy between 1999 and 2002, and blood samples were collected. Levels of adiponectin were evaluated in samples by means of a RIA. An inverse association with endometrial cancer risk emerged for plasma adiponectin levels [odds ratio (OR), 0.42; 95% confidence interval, 0.19-0.94] when comparing the highest vs. the lowest tertiles. Similar results emerged for serum adiponectin (OR, 0.30; 95% confidence interval, 0.14-0.68). The association was stronger in pre- than in postmenopausal women, but no significant heterogeneity was observed across strata of body mass index (BMI) or parity. BMI and adiponectin showed independent effects on the risk of endometrial cancer according to a multiplicative model (OR, 6.45 in the highest level of BMI and in the lowest one of adiponectin).

Testicular cancer incidence in eight northern European countries: secular and recent trends.

Abstract: Objective: Striking geographic variation and marked increasing secular trends characterize the incidence of testicular cancer. However, it is not known whether these patterns have attenuated in recent years and whether they are similar for seminomas and nonseminomas, the two main histologic groups of testicular cancer. Method: Cancer registry data, including 27,030 testicular cancer cases, were obtained from Denmark, Estonia, Finland, Latvia, Lithuania, Norway, Poland, and Sweden. Between 57 (Denmark) and 9 (Poland) years of registration were covered. Country-specific temporal trends were estimated, with focus on the last decade and seminomas and nonseminomas. Data from the Nordic countries were further analyzed using an age-period-cohort approach. Results: Age-standardized incidence rates increased annually by 2.6% to 4.9% during the study period, with marginal differences between seminomas and nonseminomas. In the last decade, the increasing trend attenuated only in Denmark (annual change, −0.3%; 95% confidence interval, −1.5 to 0.9). In 1995, the highest and the lowest age-standardized incidence rates (per 105) were 15.2 in Denmark and 2.1 in Lithuania. Incidence rates (i.e., for all cancers and for seminomas and nonseminomas, separately) depended chiefly on birth cohort rather than on calendar period of diagnosis (although both birth cohort and period determined the Danish incidence rates). Conclusions: Testicular cancer incidence is still increasing, with the exception of Denmark, and a large geographic difference exists. The increasing trend is mainly a birth cohort phenomenon also in recent cohorts. Temporal trends for seminomas and nonseminomas are similar, which suggests that they share important causal factors.

Ablation of PARP-1 does not interfere with the repair of DNA double-strand breaks, but compromises the reactivation of stalled replication forks

Abstract: Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant DNA end-sensing and binding molecule. Inactivation of PARP-1 by chemicals and genetic mutations slows cell proliferation, increases sister chromatid exchange (SCE), micronuclei formation and chromosome instability, and shortens telomeres. Given its affinity to DNA breaks and temporal occupation on DNA strand break sites, PARP-1 is proposed to prevent inappropriate DNA recombination. We investigated the potential role of PARP-1 in repair of DNA double-strand breaks (DSBs) and stalled replication forks. PARP-1-/- embryonic stem cells and embryonic fibroblast cells exhibited normal repair of DNA DSBs by either homologous recombination (HR) or nonhomologous end-joining (NHEJ) pathways. Inactivation of PARP-1 did not interfere with gene-targeting efficiency in ES cells. However, PARP-1-/- cells were hypersensitive to the replication damage agent hydroxyurea (HU)-induced cell death and exhibited enhanced SCE formation. Ablation of PARP-1 delayed reactivation of stalled replication forks imposed by HU and re-entry into the G2-M phase after HU release. These data indicate that PARP-1 is dispensable in HR induced by DSBs, but is involved in the repair and reactivation of stalled replication forks.

Cervical cancer screening programmes and policies in 18 European countries

Abstract: A questionnaire survey was conducted by the Epidemiology Working Group of the European Cervical Cancer Screening Network, and the International Agency for Research on Cancer, IARC, between August and December 2003 in 35 centres in 20 European countries with reliable cervical cancer incidence and/or mortality data in databanks held at IARC and WHO. The questionnaire was completed by 28 centres from 20 countries. The final tables included information on 25 centres from 18 countries. Six countries had started screening in the 1960s, whereas 10 countries or regions had started at least a pilot programme by 2003. There were six invitational and nine partially invitational programmes, the rest employing opportunistic screening only. Recommended lifetime number of smears varied from seven to more than 50. Coverage of smear test within the recommended screening interval (usually 3 or 5 years) was above 80% in three countries. Screening registration took place in 13 programmes. Eight programmes reported the rates of screen-detected cervical cancers and precursor lesions. There was wide variation in the CIN3 detection rates. International guidelines and quality assurance protocols are useful for monitoring and evaluating screening programmes systematically. Our survey indicated that the recommendations as currently given are met in only few European countries. Health authorities need to consider stronger measures and incentives than those laid out in the current set of recommendations.

Prevalence of Opisthorchis viverrini infection and incidence of cholangiocarcinoma in Khon Kaen, Northeast Thailand

Abstract: Liver cancer is the most common cancer in Khon Kaen, Northeast Thailand, because of the high incidence of cholangiocarcinoma (CHCA). Opisthorchis viverrini (OV), a liver fluke, is endemic in the area, and has been evaluated as a cause of CHCA by International Agency for Research on Cancer. Residents of 20 districts in the province were invited to attend a mobile screening programme between 1990 and 2001. Of 24 723 participants, 18 393 aged 35-69 years were tested for OV infection, by examining stools for the presence of eggs. Prevalence of infection in each district was estimated from the sample of the population who had been tested. The incidence of liver cancer in 1990-2001 was obtained for each district from the cancer registry. The average crude prevalence of OV infection in the sample subjects was 24.5%, ranging from 2.1% to 70.8% in different districts. Truncated age-standardized incidence of CHCA at ages >35 years varied threefold between districts, from 93.8 to 317.6 per 100,000 person-years. After adjustment for age group, sex and period of sampling, there was a positive association between prevalence of OV infection and incidence of CHCA at the population level. Associations between CHCA and active OV infection in individuals have become hard to demonstrate, because of effective anti-OV treatment. The relationship may, however, be clear in comparisons between populations, which, for infectious diseases, take into account the contextual effects of group exposure in determining individual outcome. The cancer registry is an appropriate tool for disease monitoring in small areas.

Estimation and projection of the national profile of cancer mortality in China: 1991-2005.

Abstract: There are no national-level data on cancer mortality in China since two surveys in 1973-1975 and 1990-1992 (a 10% sample), but ongoing surveillance systems, based on nonrandom selected populations, give an indication as to the trends for major cancers. Based on a log-linear regression model with Poisson errors, the annual rates of change for 10 cancers and all other cancers combined, by age, sex and urban/rural residence were estimated from the data of the surveillance system of the Center for Health Information and Statistics, covering about 10% of the national population. These rates of change were applied to the survey data of 1990-1992 to estimate national mortality in the year 2000, and to make projections for 2005. Mortality rates for all cancers combined, adjusted for age, are predicted to change little between 1991 and 2005 (-0.8% in men and +2.5% in women), but population growth and ageing will result in an increasing number of deaths, from 1.2 to 1.8 million. The largest predicted increases are for the numbers of female breast (+155.4%) and lung cancers (+112.1% in men, +153.5% in women). For these two sites, mortality rates will almost double. Cancer will make an increasing contribution to the burden of diseases in China in the 21st century. The marked increases in risk of cancers of the lung, female breast and large bowel indicate priorities for prevention and control. The increasing trends in young age groups for cancers of the cervix, lung and female breast suggest that their predicted increases may be underestimated, and that more attention should be paid to strategies for their prevention and control.

Pooled analysis of alcohol dehydrogenase genotypes and head and neck cancer: A HuGE review

Abstract: Possession of the fast metabolizing alleles for alcohol dehydrogenase (ADH), ADH1B*2 and ADH1C*1, and the null allele for aldehyde dehydrogenase (ALDH), ALDH2*2, results in increased acetylaldehyde levels and is hypothesized to increase the risk of head and neck cancer. To examine this association, the authors undertook a Human Genome Epidemiology review on these three genes and a pooled analysis of published studies on ADH1C. The majority of Asians had the fast ADH1B*2 and ADH1C*1 alleles, while the majority of Caucasians had the slow ADH1B*1/1 and ADH1C*1/2 genotypes. The ALDH2*2 null allele was frequently observed among Asians, though it was rarely observed in other populations. In a pooled analysis of data from seven case-control studies with a total of 1,325 cases and 1,760 controls, an increased risk of head and neck cancer was not observed for the ADH1C*1/2 genotype (odds ratio = 1.00, 95% confidence interval: 0.81, 1.23) or the ADH1C*1/1 genotype (odds ratio = 1.14, 95% confidence interval: 0.92, 1.41). Increased relative risks of head and neck cancer were reported for the ADH1B*1/1 and ALDH2*1/2 genotypes in several studies. Recommendations for future studies include larger sample sizes and incorporation of relevant ADH and ALDH genes simultaneously, as well as other genes. These considerations suggest the potential for the organization of a consortium of investigators conducting studies in this field.

Improved estimates of floating absolute risk

Abstract: Floating absolute risks are an alternative way of presenting relative risk estimates for polychotomous risk factors. Instead of choosing one level of the risk factor as a reference category, each level is assigned a 'floated' variance which describes the uncertainty in risk without reference to another level. In this paper, a method for estimating the floated variances is presented that improves on the previously proposed 'heuristic' method. The estimates may be calculated iteratively with a simple algorithm. A benchmark for validating the floated variance estimates is also proposed and an interpretation of floating confidence intervals is given.

Cervical cancer as a priority for prevention in different world regions: an evaluation using years of life lost.

Abstract: The relative importance of cancer of the cervix among several important causes of mortality (from cancer and other diseases) has been evaluated by estimating the years of life lost (YLL) by young and middle-aged women (25-64 years old) in different regions of the world. The life years were weighted to reflect their importance to the individual and to society. On a global basis, cancer of the cervix is responsible for about 2% of the total (weighted) YLL, fewer than for other causes of mortality in this age group. However, it is the most important cause of YLL in Latin America and the Caribbean. It also makes the largest contribution to YLL from cancer in the populous regions of SubSaharan Africa and South-Central Asia where the actual risk of loss of life from this cause is higher, although overshadowed by noncancer deaths (from AIDS, TB and maternal conditions). The overall picture is not very sensitive to the age weighting function used. The fact that most of the loss of life is preventable, and that simple technologies have been developed that make this practicable, means that cervical cancer has an even higher profile from the perspective of resource allocation in low income settings.

Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women.

Abstract: Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre-diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case-control study was nested within 3 cohorts in New York (USA), Umea (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76-9.72), p(trend) = 0.0008 for estradiol, 3.67 (1.71-7.88), p(trend) = 0.0007 for estrone, 2.15 (1.05-4.40), p(trend) = 0.04 for androstenedione, 1.74 (0.88-3.46), p(trend) = 0.06 for testosterone, 2.90 (1.42-5.90), p(trend) = 0.002 for DHEAS and 0.46 (0.20-1.05), p(trend) = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis.

A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA.

Abstract: We undertook a case–control study to examine the possible associations of the TP53 variants Arg>Pro at codon 72 and p53PIN3, a 16 bp insertion/duplication in intron 3, with the risk of colorectal cancer (CRC). The p53PIN3 A2 allele (16 bp duplication) was associated with an increased risk (OR 1.55, 95% CI 1.10−2.18, P=0.012), of the same order of magnitude as that observed in previous studies for other types of cancer. The Pro72 allele was weakly associated with CRC (OR=1.34, 95% CI 0.98−1.84, P=0.066). The possible functional role of p53PIN3 was investigated by examining the TP53 mRNA transcripts in 15 lymphoblastoid cell lines with different genotypes. The possibility that the insertion/deletion could lead to alternatively spliced mRNAs was excluded. However, we found reduced levels of TP53 mRNA associated with the A2 allele. In conclusion, the epidemiological study suggests a role for p53PIN3 in tumorigenesis, supported by the in vitro characterization of this variant.

Prevalence of papillomavirus infection in women in Ibadan, Nigeria: a population-based study.

Abstract: Prevalence of papillomavirus infection in women in Ibadan, Nigeria: a population-based study

Prevalence and determinants of genital infection with Papillomavirus, in female and male university students in Busan. South Korea

Abstract: Background. Little is known about the prevalence of human papillomavirus (HPV) infection in young adults in Asia. Methods. We invited female and male students in Busan, South Korea, to participate in a survey that included, for females, self-collection of vaginal cells and, for males, physician-performed collection of exfoliated genital cells. The prevalences of 25 HPV types were evaluated, by a polymerase chain reaction-based assay, in 672 female students (median age, 19 years) and in 381 male students (median age, 22 years). Results. HPV DNA was detected more frequently in female students (15.2%) than in male students (8.7%); in both sexes, high-risk HPV types were predominant. Among sexually active students, HPV prevalence was 38.8% in females and 10.6% in males. In female students, currently smoking cigarettes and having multiple lifetime sex partners were the strongest risk factors for HPV infection; in male students, associations between HPV prevalence and sexual habits were similar to those in female students but never attained statistical significance. Conclusions. Young women in South Korea start having penetrative sexual intercourse relatively late (median age, 18 years), but, once they begin, HPV prevalence quickly rises to levels comparable with those found in university students in the United States and in northern Europe. The high rate of participation in our study suggests that trials of new vaccines against HPV may be feasible among university students in South Korea.