Cristina Bosetti

Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study.

BACKGROUND High parity has long been suspected of being associated with an increased risk of cervical cancer, but previous analyses of this association have not taken the strong effect of human papillomavirus (HPV) into account. To assess the role of reproductive factors in the progression from HPV infection to cancer, we did a pooled analysis including only HPV-positive women. METHODS We pooled data from eight case-control studies on invasive cervical carcinoma (ICC) and two on in-situ carcinoma (ISC) from four continents. 1465 patients with squamous-cell ICCs, 211 with ISCs, 124 with adenocarcinomas or adenosquamous ICCs, and 255 control women, all positive for HPV DNA by PCR-based assays, were analysed. We calculated pooled odds ratios by means of unconditional multiple logistic regression models, and adjusted them for sexual and non-sexual confounding factors. The 95% CI were estimated by treating the odds ratio as floating absolute risk. FINDINGS We found a direct association between the number of full-term pregnancies and squamous-cell cancer risk: the odds ratio for seven full-term pregnancies or more was 3.8 (95% CI 2.7-5.5) compared with nulliparous women, and 2.3 (1.6-3.2) compared with women who had one or two full-term pregnancies. There was no significant association between risk of adenocarcinoma or adenosquamous carcinoma and number of full-term pregnancies. INTERPRETATION High parity increases the risk of squamous-cell carcinoma of the cervix among HPV-positive women. A general decline in parity might therefore partly explain the reduction in cervical cancer recently seen in most countries.

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

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.

Worldwide trends in gastric cancer mortality (1980-2011), with predictions to 2015, and incidence by subtype.

Gastric cancer incidence and mortality decreased substantially over the last decades in most countries worldwide, with differences in the trends and distribution of the main topographies across regions. To monitor recent mortality trends (1980-2011) and to compute short-term predictions (2015) of gastric cancer mortality in selected countries worldwide, we analysed mortality data provided by the World Health Organization. We also analysed incidence of cardia and non-cardia cancers using data from Cancer Incidence in Five Continents (2003-2007). The joinpoint regression over the most recent calendar periods gave estimated annual percent changes (EAPC) around -3% for the European Union (EU) and major European countries, as well as in Japan and Korea, and around -2% in North America and major Latin American countries. In the United States of America (USA), EU and other major countries worldwide, the EAPC, however, were lower than in previous years. The predictions for 2015 show that a levelling off of rates is expected in the USA and a few other countries. The relative contribution of cardia and non-cardia gastric cancers to the overall number of cases varies widely, with a generally higher proportion of cardia cancers in countries with lower gastric cancer incidence and mortality rates (e.g. the USA, Canada and Denmark). Despite the favourable mortality trends worldwide, in some countries the declines are becoming less marked. There still is the need to control Helicobacter pylori infection and other risk factors, as well as to improve diagnosis and management, to further reduce the burden of gastric cancer.

Aspirin and cancer risk: a quantitative review to 2011

BACKGROUND Aspirin has been associated to a reduced risk of colorectal and possibly of a few other common cancers. METHODS To provide an up-to-date quantification of this association, we conducted a meta-analysis of all observational studies on aspirin and 12 selected cancer sites published up to September 2011. RESULTS Regular aspirin is associated with a statistically significant reduced risk of colorectal cancer [summary relative risk (RR) from random effects models = 0.73, 95% confidence interval (CI) 0.67-0.79], and of other digestive tract cancers (RR = 0.61, 95% CI = 0.50-0.76, for squamous cell esophageal cancer; RR = 0.64, 95% CI = 0.52-0.78, for esophageal and gastric cardia adenocarcinoma; and RR = 0.67, 95% CI = 0.54-0.83, for gastric cancer), with somewhat stronger reductions in risk in case-control than in cohort studies. Modest inverse associations were also observed for breast (RR = 0.90, 95% CI = 0.85-0.95) and prostate cancer (RR = 0.90, 95% CI = 0.85-0.96), while lung cancer was significantly reduced in case-control studies (0.73, 95% CI = 0.55-0.98) but not in cohort ones (RR = 0.98, 95% CI = 0.92-1.05). No meaningful overall associations were observed for cancers of the pancreas, endometrium, ovary, bladder, and kidney. CONCLUSIONS Observational studies indicate a beneficial role of aspirin on colorectal and other digestive tract cancers; modest risk reductions were also observed for breast and prostate cancer. Results are, however, heterogeneous across studies and dose-risk and duration-risk relationships are still unclear.

Mechanisms of Disease: the epidemiology of bladder cancer

Mortality from bladder cancer has shown downward trends over the last 2 decades in several western European countries (albeit 10–15 years later than similar trends in the US), but is still increasing in some eastern European countries. Tobacco smoking and occupational exposure to aromatic amines are the two major established environmental risk factors for bladder cancer. Controlling exposure to these factors has been an important contributor to the reduction in bladder cancer mortality, particularly among men. Diet could influence bladder carcinogenesis, as many compounds contained in foods—and their metabolites—are excreted through the urinary tract. Fruit and vegetable consumption was inversely related with bladder cancer in many studies, but no consistent association has emerged between intake of related micronutrients and reduced risk of bladder cancer. Other widely investigated lifestyle habits are probably not associated with risk of developing bladder cancer (e.g. coffee consumption, artificial sweetener use, hair dyes) or are difficult to assess (e.g. fluid intake). Infections and stones in the urinary tract might cause chronic irritation of the bladder epithelium, and thus increase bladder cancer risk. First-degree relatives of bladder cancer patients have a 50–100% increased relative risk of developing the disease, a risk that could be even higher when the proband is diagnosed at an early age.

Trends in mortality from hepatocellular carcinoma in Europe, 1980‐2004

Upward trends in mortality from hepatocellular carcinoma (HCC) were recently reported in the United States and Japan. Comprehensive analyses of most recent data for European countries are not available. Age‐standardized (world standard) HCC rates per 100,000 (at all ages, at age 20‐44, and age 45‐59 years) were computed for 23 European countries over the period 1980‐2004 using data from the World Health Organization. Joinpoint regression analysis was used to identify significant changes in trends, and annual percent change were computed. Male overall mortality from HCC increased in Austria, Germany, Switzerland, and other western countries, while it significantly decreased over recent years in countries such as France and Italy, which had large upward trends until the mid‐1990s. In the early 2000s, among countries allowing distinction between HCC and other liver cancers, the highest HCC rates in men were in France (6.8/100,000), Italy (6.7), and Switzerland (5.9), whereas the lowest ones were in Norway (1.0), Ireland (0.8), and Sweden (0.7). In women, a slight increase in overall HCC mortality was observed in Spain and Switzerland, while mortality decreased in several other European countries, particularly since the mid‐1990s. In the early 2000s, female HCC mortality rates were highest in Italy (1.9/100,000), Switzerland (1.8), and Spain (1.5) and lowest in Greece, Ireland, and Sweden (0.3). In most countries, trends at age 45‐59 years were consistent with overall ones, whereas they were more favorable at age 20‐44 years in both sexes. Conclusion: HCC mortality remains largely variable across Europe. Favorable trends were observed in several European countries mainly over the last decade, particularly in women and in young adults. (HEPATOLOGY 2008.)

Hepatocellular carcinoma epidemiology

Primary liver cancer (namely hepatocellular carcinoma, HCC) is worldwide the fifth most common cancer in men and the seventh one in women, and it represents the third most frequent cause of cancer death. HCC rates are particularly high in eastern/south-eastern Asia and in Africa, intermediate in Southern Europe, and low in most high-income countries. Persistent infections by HBV or HCV are the main recognized risk factors for HCC. Aflatoxin exposure is also an important risk factor for HCC development in Africa and eastern Asia. In high-income countries heavy alcohol drinking, tobacco smoking, overweight, diabetes, familial/genetic factors, and selected dietary aspects, have a relevant role. Updated geographic patterns and time trends in mortality from HCC in Europe, USA, Japan, and Australia are provided in the present review, together with an overview of relevant etiologic factors for HCC and main measures for the prevention of this neoplasm.

Coffee drinking and hepatocellular carcinoma risk: A meta‐analysis

Several studies suggest an inverse relation between coffee drinking and risk of hepatocellular carcinoma (HCC). We conducted a meta‐analysis of published studies on HCC that included quantitative information on coffee consumption. Ten studies were retrieved (2,260 HCC cases), including 6 case–control studies from southern Europe and Japan (1551 cases) and 4 cohort studies from Japan (709 cases). The summary relative risk (RR) for coffee drinkers versus non‐drinkers was 0.54 (95% confidence interval [CI] 0.38‐0.76) for case–control studies and 0.64 (95% CI 0.56‐0.74) for cohort studies. The overall RR was 0.59 (95% CI 0.49‐0.72), with significant heterogeneity between studies. The overall summary RR for low or moderate coffee drinkers was 0.70 (95% CI 0.57‐0.85), and that for high drinkers was 0.45 (95% CI 0.38‐0.53). The summary RR for an increase of 1 cup of coffee per day was 0.77 (95% CI 0.72‐0.83) from case–control studies, 0.75 (95% CI 0.65‐0.85) from cohort studies, and 0.77 (95% CI 0.72‐0.82) overall. The consistency of an inverse relation between coffee drinking and HCC across study design and geographic areas weighs against a major role of bias or confounding. Coffee drinking has also been related to reduced risk of other liver diseases, thus suggesting a continuum of the favorable effect of coffee on liver function. However, subjects with liver conditions may selectively reduce their coffee consumption. Conclusion: The present analysis provides evidence that the inverse relation between coffee and HCC is real, though inference on causality remains open to discussion. (HEPATOLOGY 2007.)

Combined effect of tobacco and alcohol on laryngeal cancer risk: a case-control study

Objective: To provide information on the effects of alcohol and tobacco on laryngeal cancer and its subsites. Methods: This was a case–control study conducted between 1992 and 2000 in northern Italy and Switzerland. A total of 527 cases of incident squamous-cell carcinoma of the larynx and 1297 hospital controls frequency-matched with cases on age, sex, and area of residence were included. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression. Results: In comparison with never smokers, ORs were 19.8 for current smokers and 7.0 for ex-smokers. The risk increased in relation to the number of cigarettes (OR = 42.9 for ≥25 cigarettes/day) and for duration of smoking (OR = 37.2 for ≥40 years). For alcohol, the risk increased in relation to number of drinks (OR = 5.9 for ≥56 drinks per week). Combined alcohol and tobacco consumption showed a multiplicative (OR = 177) rather than an additive risk. For current smokers and current drinkers the risk was higher for supraglottis (ORs 54.9 and 2.6, respectively) than for glottis (ORs 7.4 and 1.8) and others subsites (ORs 10.9 and 1.9). Conclusions: Our study shows that both cigarette smoking and alcohol drinking are independent risk factors for laryngeal cancer. Heavy consumption of alcohol and cigarettes determined a multiplicative risk increase, possibly suggesting biological synergy.

Cancer Risk Associated with Use of Metformin and Sulfonylurea in Type 2 Diabetes: A Meta-Analysis

OBJECTIVE Oral antidiabetic drugs (including metformin and sulfonylurea) may play a role in the relationship between type 2 diabetes and cancer. To quantify the association between metformin and sulfonylurea and the risk of cancer, we performed a meta-analysis of available studies on the issue. MATERIALS AND METHODS We performed a MEDLINE search for observational studies that investigated the risk of all cancers and specific cancer sites in relation to use of metformin and/or sulfonylurea among patients with type 2 diabetes mellitus. Fixed- and random-effect models were fitted to estimate the summary relative risk (RR). Between-study heterogeneity was tested using χ(2) statistics and measured with the I(2) statistic. Publication bias was evaluated using funnel plot and Eggers regression asymmetry test. RESULTS Seventeen studies satisfying inclusion criteria and including 37,632 cancers were evaluated after reviewing 401 citations. Use of metformin was associated with significantly decreased RR of all cancers (summary RR 0.61, 95% confidence interval [CI] 0.54-0.70), colorectal cancer (0.64, 95% CI 0.54-0.76), and pancreatic cancer (0.38, 95% CI 0.14-0.91). With the exception of colorectal cancer, significant between-study heterogeneity was observed. Evidence of publication bias for metformin-cancer association was also observed. There was no evidence that metformin affects the risk of breast and prostate cancers, nor that sulfonylurea affects the risk of cancer at any site. CONCLUSIONS Metformin, but not sulfonylurea, appears to reduce subsequent cancer risk. This has relevant implications in light of the exploding global epidemic of diabetes.