Valentina Rosato

Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial.

The efficacy and cost-effectiveness of low-dose spiral computed tomography (LDCT) screening in heavy smokers is currently under evaluation worldwide. Our screening program started with a pilot study on 1035 volunteers in Milan in 2000 and was followed up in 2005 by a randomized trial comparing annual or biennial LDCT with observation, named Multicentric Italian Lung Detection. This included 4099 participants, 1723 randomized to the control group, 1186 to biennial LDCT screening, and 1190 to annual LDCT screening. Follow-up was stopped in November 2011, with 9901 person-years for the pilot study and 17 621 person-years for Multicentric Italian Lung Detection. Forty-nine lung cancers were detected by LDCT (20 in biennial and 29 in the annual arm), of which 17 were identified at baseline examination; 63% were of stage I and 84% were surgically resectable. Stage distribution and resection rates were similar in the two LDCT arms. The cumulative 5-year lung cancer incidence rate was 311/100 000 in the control group, 457 in the biennial, and 620 in the annual LDCT group (P=0.036); lung cancer mortality rates were 109, 109, and 216/100 000 (P=0.21), and total mortality rates were 310, 363, and 558/100 000, respectively (P=0.13). Total mortality in the pilot study was similar to that observed in the annual LDCT arm at 5 years. There was no evidence of a protective effect of annual or biennial LDCT screening. Furthermore, a meta-analysis of the four published randomized trials showed similar overall mortality in the LDCT arms compared with the control arm.

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.

Recent trends in colorectal cancer mortality in Europe.

Colorectal cancer mortality has been declining over the last two decades in Europe, particularly in women, the trends being, however, different across countries and age groups. We updated to 2007 colorectal cancer mortality trends in Europe using data from the World Health Organization (WHO). Rates were analyzed for the overall population and separately in young, middle‐age and elderly populations. In the European Union (EU), between 1997 and 2007 mortality from colorectal cancer declined by around 2% per year, from 19.7 to 17.4/100,000 men (world standardized rates) and from 12.5 to 10.5/100,000 women. Persisting favorable trends were observed in countries of western and northern Europe, while there were more recent declines in several countries of eastern Europe, including the Czech Republic, Hungary and Slovakia particularly in women (but not Romania and the Russian Federation). In 2007, a substantial excess in colorectal cancer mortality was still observed in Slovakia, Hungary, Croatia, the Czech Republic and Slovenia in men (rates over 25/100,000), and in Hungary, Norway, Denmark and Slovakia in women (rates over 14/100,000). Colorectal mortality trends were more favorable in the young (30–49 years) from most European countries, with a decline of ∼2% per year since the early 1990s in both men and women from the EU. The recent decreases in colorectal mortality rates in several European countries are likely due to improvements in (early) diagnosis and treatment, with a consequent higher survival from the disease. Interventions to further reduce colorectal cancer burden are, however, still warranted, particularly in eastern European countries.

Cancer Risk for Patients Using Thiazolidinediones for Type 2 Diabetes: A Meta-Analysis

OBJECTIVE To clarify and quantify the effect of thiazolidinediones (TZDs; e.g., pioglitazone, rosiglitazone) on the risk of bladder cancer, other selected cancers, and overall cancer in patients with type 2 diabetes, we performed a systematic review and meta-analysis of observational studies. METHODS A PubMed/MEDLINE search was conducted for studies published in English up to June 30, 2012. Random-effect models were fitted to estimate summary relative risks (RR). RESULTS Seventeen studies satisfying inclusion criteria (3 case-control studies and 14 cohort studies) were considered. Use of TZDs was not associated to the risk of cancer overall (summary RR: 0.96; 95% confidence interval [CI]: 0.91-1.01). A modest excess risk of bladder cancer was reported in pioglitazone (RR: 1.20; 95% CI: 1.07-1.34 from six studies) but not in rosiglitazone (RR: 1.08; 95% CI: 0.95-1.23 from three studies) users. The RRs of bladder cancer were higher for longer duration (RR: 1.42 for >2 years) and higher cumulative dose of pioglitazone (RR: 1.64 for >28,000 mg). Inverse relations were observed with colorectal cancer (RR: 0.93; 95% CI: 0.90-0.97 from six cohort studies) and liver cancer (RR: 0.65; 95% CI: 0.48-0.89 from four studies), whereas there was no association with pancreatic, lung, breast, and prostate cancers. CONCLUSIONS Adequate evidence excludes an overall excess cancer risk in TZD users within a few years after starting treatment. However, there is a modest excess risk of bladder cancer, particularly with reference to pioglitazone. Assuming that this association is real, the potential implications on the risk-benefit analysis of TZD use should be evaluated.

Metabolic syndrome and the risk of breast cancer in postmenopausal women

BACKGROUND Only a few small studies investigated the association between postmenopausal breast cancer and metabolic syndrome (MetS) as a single entity. MATERIALS AND METHODS We analyzed the data of two Italian and Swiss case-control studies conducted between 1983 and 2007, including 3869 postmenopausal women with incident breast cancer and 4082 postmenopausal controls admitted to the same hospitals as cases for acute conditions. MetS was defined as the presence of at least three components among diabetes, drug-treated hypertension, drug-treated hyperlipidemia, and obesity. RESULTS The odds ratios (ORs) of postmenopausal breast cancer were 1.33 [95% confidence interval (CI) 1.09-1.62] for diabetes, 1.19 (95% CI 1.07-1.33) for hypertension, 1.08 (95% CI 0.95-1.22) for hyperlipidemia, 1.26 (95% CI 1.11-1.44) for body mass index ≥30 kg/m(2), and 1.22 (95% CI 1.09-1.36) for waist circumference ≥88 cm. The risk of postmenopausal breast cancer was significantly increased for women with MetS (OR = 1.75, 95% CI 1.37-2.22, for three or more MetS components, P for trend for increasing number of components < 0.0001) and the risk was higher at older age (OR = 3.04, 95% CI 1.75-5.29, at age ≥70 years for three or more MetS components). CONCLUSIONS This study supports a direct association between MetS and postmenopausal breast cancer risk.

Metabolic syndrome and endometrial cancer risk

BACKGROUND Various studies reported direct associations between endometrial cancer risk and individual components of the metabolic syndrome (MetS), i.e. obesity, diabetes, hypertension, and dyslipidemia, but only a few epidemiological studies considered the association with MetS overall. METHODS We analyzed data from a case-control study including 454 women with incident endometrial cancer and 798 controls admitted to the same hospitals as cases for acute conditions. Different definitions of MetS were considered, including a combination of self-reported history of diabetes, drug-treated hypertension, drug-treated hyperlipidemia, and various measures of (central) obesity. Odds ratios (ORs) were computed from unconditional logistic regression models, adjusted for major confounding factors. RESULTS The multivariate ORs of endometrial cancer were 2.18 for type 2 diabetes, 1.77 for hypertension, 1.20 for hyperlipidemia, between 1.62 and 2.23 for various definitions of central obesity, and 3.83 for women with a body mass index (BMI) >30 kg/m(2). The risk of endometrial cancer was significantly increased for subjects with MetS, the ORs ranging between 1.67 and 2.77 when waist circumference was included in MetS definition, and 8.40 when BMI was considered instead. CONCLUSIONS This study indicates a direct association between various MetS components, besides overweight, with the risk of endometrial cancer.

Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium

BACKGROUND Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). CONCLUSION This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.

Diabetes Mellitus and Cancer Risk in a Network of Case-Control Studies

Diabetes has been associated to the risk of a few cancer sites, though quantification of this association in various populations remains open to discussion. We analyzed the relation between diabetes and the risk of various cancers in an integrated series of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1,468 oral and pharyngeal, 505 esophageal, 230 gastric, 2,390 colorectal, 185 liver, 326 pancreatic, 852 laryngeal, 3,034 breast, 607 endometrial, 1,031 ovarian, 1,294 prostate, and 767 renal cell cancer cases and 12,060 hospital controls. The multivariate odds ratios (OR) for subjects with diabetes as compared to those without—adjusted for major identified confounding factors for the cancers considered through logistic regression models—were significantly elevated for cancers of the oral cavity/pharynx (OR = 1.58), esophagus (OR = 2.52), colorectum (OR = 1.23), liver (OR = 3.52), pancreas (OR = 3.32), postmenopausal breast (OR = 1.76), and endometrium (OR = 1.70). For cancers of the oral cavity, esophagus, colorectum, liver, and postmenopausal breast, the excess risk persisted over 10 yr since diagnosis of diabetes. Our data confirm and further quantify the association of diabetes with colorectal, liver, pancreatic, postmenopausal breast, and endometrial cancer and suggest forthe first time that diabetes may also increase the risk of oral/pharyngeal and esophageal cancer. TABLE 1 Number of cases of selected cancer sites and controls and corresponding median age in Italy and Switzerland, 1991–2009 Cases Median Controls Median Cancer site (References) (men/women) age (yr) (men/women) age (yr) Oral cavity and pharynx (10,11) 1190/278 58 2553/1208 58 Esophagus (12,13) 438/67 60 919/340 60 Gastric (14) 143/87 63 286/261 63 Colorectum (15,16) 1401/989 62 2586/2357 58 Liver (17) 149/36 66 278/126 65 Pancreas (18) 174/152 63 348/304 63 Larynx (19) 770/82 62 1564/406 61 Breast (20,21) –/3034 55 –/3392 56 Endometrium (22) –/607 62 –/1366 61 Ovary (23) –/1031 56 –/2411 57 Prostate (24) 1294/– 66 1451/– 63 Renal cell cancer (25) 494/273 62 988/546 62 TABLE 2 Distribution of cases of selected cancer sites and corresponding controls, and odds ratios (OR) and 95% confidence intervals (CI) according to history of diabetes in Italy and Switzerland, 1991–2009 History of diabetes No Yes Cancer site Cases (%) Controls (%) Cases (%) Controls (%) ORa (95% CI) ORb (95% CI) Oral cavity and pharynx 1370 (93.3) 3580 (95.2) 98 (6.7) 181 (4.8) 1.34 (0.98–1.85) 1.58 (1.15–2.18) Esophagus 455 (90.1) 1197 (95.1) 50 (9.9) 62 (4.9) 2.22 (1.36–3.63) 2.52 (1.54–4.13) Gastric 213 (92.6) 504 (92.1) 17 (7.4) 43 (7.9) 0.94 (0.51–1.73) 0.98 (0.53–1.81) Colorectum 2229 (93.3) 4722 (95.5) 161 (6.7) 221 (4.5) 1.23 (0.99–1.53) 1.23 (0.98–1.53) Colon 1371 (93.7) 4722 (95.5) 92 (6.3) 221 (4.5) 1.17 (0.90–1.52) 1.16 (0.89–1.50) Rectum 858 (92.6) 4722 (95.5) 69 (7.4) 221 (4.5) 1.36 (1.02–1.83) 1.38 (1.03–1.86) Liver 145 (78.4) 377 (93.3) 40 (21.6) 27 (6.7) 3.42 (1.89–6.18) 3.52 (1.94–6.39) Pancreas 269 (82.5) 615 (94.3) 57 (17.5) 37 (5.7) 3.18 (1.95–5.20) 3.32 (2.02–5.44) Larynx 782 (91.8) 1836 (93.2) 70 (8.2) 134 (6.8) 1.23 (0.86–1.74) 1.30 (0.91–1.85) Breast/pre–perimenopausec 1134 (98.6) 1165 (98.7) 16 (1.4) 15 (1.3) 1.35 (0.64–2.86) 1.50 (0.70–3.21) Breast/postmenopausec 1750 (92.9) 2103 (95.1) 134 (7.1) 109 (4.9) 1.83 (1.39–2.40) 1.76 (1.34–2.32) Endometriumd 545 (89.8) 1300 (95.2) 62 (10.2) 66 (4.8) 2.08 (1.41–3.06) 1.70 (1.14–2.53) Ovaryd 986 (95.6) 2324 (96.4) 45 (4.4) 87 (3.6) 1.24 (0.82–1.86) 1.21 (0.80–1.82) Prostate 1205 (93.1) 1352 (93.2) 89 (6.9) 99 (6.8) 0.91 (0.66–1.26) 0.92 (0.66–1.27) Renal cell 697 (90.9) 1423 (92.8) 70 (9.1) 111 (7.2) 1.30 (0.94–1.80) 1.26 (0.91–1.75) aEstimates from logistic regression model adjusted for sex (when appropriate), age, study center, year of interview, education, alcohol drinking, and tobacco smoking. Reference category: no history of diabetes. bFurther adjusted for body mass index. cFurther adjusted for age at first birth, parity, age at menopause (when appropriate), oral contraceptives use, and hormone replacement therapy use. dFurther adjusted for parity, menopausal status, age at menopause, oral contraceptives use, and hormone replacement therapy use.

Metabolic syndrome and pancreatic cancer risk: a case-control study in Italy and meta-analysis.

We assessed the relation between metabolic syndrome (MetS), its components, and pancreatic cancer risk in an Italian case-control study and performed a meta-analysis of epidemiological studies published up to February 2011. The case-control study included 326 patients with incident pancreatic cancer and 652 controls admitted to the same hospitals for acute, non-neoplastic conditions. MetS was defined as having at least 3 conditions among diabetes, drug-treated hypertension, hyperlipidemia, and body mass index at least 25 kg/m(2) at age 30 years. We computed multivariate odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) from logistic regression models adjusted for tobacco smoking, education, and other sociodemographic variables. For the meta-analysis, we calculated summary relative risks (RRs) using random-effects models. The OR of pancreatic cancer in the case-control study was 2.36 (95% CI, 1.43-3.90) for diabetes, 0.77 (95% CI, 0.55-1.08) for hypertension, 1.38 (95% CI, 0.94-2.01) for hypercholesterolemia, and 1.27 (95% CI, 0.91-1.78) for being overweight at age 30 years. The risk was significantly increased for subjects with 3 or more MetS components (OR = 2.13, 95% CI 1.01-4.49) compared with subjects with no component, the estimates being consistent among strata of sex, age, and alcohol consumption. The meta-analysis included 3 cohort studies and our case-control study, and found a summary RR of 1.55 (95% CI, 1.19-2.01) for subjects with MetS. Metabolic syndrome is related to pancreatic cancer risk. Diabetes is the key component related to risk.

Flavonoids, proanthocyanidins, and the risk of stomach cancer

Flavonoids have been suggested to be responsible for the potential beneficial properties of fruit and vegetables on stomach cancer risk. To provide further information on flavonoids, proanthocyanidins, and gastric cancer risk, we analyzed data from a case–control study conducted in Italy. Subjects were 230 cases with incident, histologically confirmed gastric cancer and 547 frequency-matched controls, admitted to the same hospitals of cases for acute, non-neoplastic conditions. Subjects were interviewed using a reproducible and valid food frequency questionnaire. We estimated the odds ratios (ORs) of gastric cancer and their corresponding 95% confidence intervals (CIs) using unconditional logistic regression models including terms for major recognized gastric cancer risk factors. The ORs of the highest quintile of intake compared to the lowest were below unity for all classes of flavonoids, in the absence, however, of significant associations. Strong inverse relations were found for proanthocyanidins. The OR was 0.44 (95% CI, 0.25–0.76) for monomers and dimers combined and 0.36 (95% CI, 0.21–0.63) for polymers with three or more mers. Further adjustment for fruit and vegetables, or vitamin C, did not materially change these associations. This is the first epidemiological study to suggest that dietary proanthocyanidins have a favorable role on gastric cancer risk.