Vascular endothelial growth factor -634G/C and vascular endothelial growth factor -2578C/A polymorphisms and lung cancer risk: a case–control study and meta-analysis

Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis in the process of tumor growth and metastasis. In present study, we conducted a case–control study and meta-analysis to evaluate the genetic effects of VEGF -634G/C and VEGF -2578C/A polymorphisms and risk of lung cancer. A total of 175 subjects were recruited for case–control study and seven studies were included in the meta-analysis. Our case–control study showed that VEGF -634G/C polymorphism had no association with lung cancer risk (CC vs. GG: OR?=?0.88, 95 % CI?=?0.37–2.11), whereas there was an association between VEGF -2578CC genotype and decrease in lung cancer risk (CC vs. CA/AA: OR?=?0.52, 95 % CI?=?0.28–0.96). A meta-analysis was further performed and statistically similar results were obtained (CC vs. GG: OR?=?0.91, 95 % CI?=?0.60–1.39 for VEGF ?634; CC vs. AA: OR?=?0.53, 95 % CI?=?0.32–0.89 for VEGF ?2578). Our study showed that the variant genotypes of the VEGF -2578C/A polymorphism, but not the VEGF -634G/C polymorphism, was associated with lung cancer risk. More studies are needed to detect VEGF -634G/C and VEGF ?2578 polymorphisms and their association with lung cancer in different ethnic populations incorporated with environmental exposures.     

GH1 T1663A polymorphism and cancer risk: a meta-analysis of case–control studies

Many studies have demonstrated that the most common polymorphism (T1663A, rs2665802) in the promoter region of growth hormone 1 (GH1) gene might play an important role in cancer development and progression. This meta-analysis aims to investigate a more precise estimation of the relationship between GH1 T1663A polymorphism and cancer risk. We searched CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, and CBM databases from inception through October 1st, 2013. Meta-analysis was performed using the STATA 12.0 software. Seven studies were included with a total of 4,018 cancer patients and 5,308 healthy controls. Our meta-analysis results revealed that GH1 T1663A polymorphism was associated with increased cancer risks. Subgroup analysis by cancer type showed significant associations between GH1 T1663A polymorphism and increased colorectal cancer risk, but there was no evidence of any association with breast cancer. Further subgroup analysis based on ethnicity indicated that GH1 T1663A polymorphism might increase cancer risks among Asian populations. However, no statistically significant association was found among Caucasian populations. Meta-regression analyses also suggested that cancer type and ethnicity may be the main sources of heterogeneity. No publication bias was detected in this meta-analysis. The present meta-analysis indicates that GH1 T1663A polymorphism may contribute to the risk of colorectal cancer, especially among Asian populations.     

Vascular endothelial growth factor (VEGF) −2578C/A and −460C/T gene polymorphisms and lung cancer risk: a meta-analysis involving 11 case–control studies

The aim of this meta-analysis is to generate large-scale evidence on whether common vascular endothelial growth factor (VEGF) gene polymorphisms (–2578C/A [dbSNP: rs699947] and ?460C/T [dbSNP: rs833061]) are associated with lung cancer. A literature search of PubMed, Embase, Web of Science, Cochrane Library, and CBM databases was conducted to identify all eligible studies published before May 3, 2013. Crude odds ratios (ORs) with their corresponding confidence intervals (95 % CIs) were used to evaluate the strength of the association. Eleven case–control studies were included with a total of 3,861 lung cancer cases and 3,676 controls in this meta-analysis. For the VEGF ?2578C/A polymorphism, the combined results showed that there exist highly significant risk factors for individuals carrying the A allele resulting in lung cancer, and the magnitude of this effect was similar in smoker patients and squamous cell carcinoma (SCC) patients. Unlike the situation with the ?2578C/A polymorphism, the VEGF ?460C/T polymorphism is not associated with the risk of lung cancer in neither Asians nor Caucasians. However, when stratified according to smoking status and histological types of lung cancer, we found that the T allele (?460C/T) was associated with decreased lung cancer risk among nonsmoker patients and SCC patients. Our findings showed that the ?2578C/A polymorphism may increase lung cancer risk, especially in smoker patients and SCC patients, whereas the ?460C/T polymorphism may decrease lung cancer risk, especially in nonsmoker patients and SCC patients.     

Coffee consumption and risk of colorectal cancer: a meta-analysis of case–control studies

A meta-analysis of case–control studies on coffee consumption and colorectal cancer risk was conducted. Twenty-four eligible studies published before May 2010 were identified, including a total of 14,846 cases of colorectal, colon or rectal cancer. Compared to non/occasional drinkers, the odds ratios (OR) for drinkers were 0.83 (95% CI 0.73–0.95) for colorectal, 0.93 (95% CI 0.81–1.07) for colon and 0.98 (95% CI 0.85–1.13) for rectal cancer, with significant heterogeneity among studies; the corresponding ORs for the increment of 1 cup/day were 0.94 (95% CI 0.91–0.98), 0.95 (95% CI 0.92–0.98), and 0.97 (95% CI 0.95–0.99). For the highest coffee drinkers, the ORs were 0.70 (95% CI 0.60–0.81) for colorectal cancer, 0.75 (95% CI 0.64–0.88) for colon cancer and 0.87 (95% CI 0.75–1.00) for rectal cancer, when compared to non/low drinkers. The results of this meta-analysis of case–control studies suggest a moderate favorable effect of coffee consumption on colorectal cancer risk. The reduced risk was consistent across study design (hospital vs. population based), geographic area, and various confounding factors considered. It may reflect a real protection but also partly or largely be due to reverse causation, i.e. decreased coffee consumption among cases following the onset of bowel symptoms.     

Transforming growth factor-β1 polymorphisms and breast cancer risk: a meta-analysis based on 27 case–control studies

The association between transforming growth factor-β1 (TGF-β1) gene polymorphisms and breast cancer risk has been widely reported, but results were somewhat controversial and underpowered. To derive a more precise estimation of the relationship between TGF-β1 polymorphisms and breast cancer risk, we conducted a meta-analysis of all available case–control studies relating the T869C and/or C-509T polymorphisms of the TGF-β1 gene to the risk of developing breast cancer. Eligible articles were identified by search of databases including MEDLINE, PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature database (CBM) for the period up to March 2010. Finally, a total of 17 articles involving 27 case–control studies were identified, 25 with 20,022 cases and 24,423 controls for T869C polymorphism and eight with 10,633 cases and 13,648 controls for C-509T polymorphism. The pooled ORs were performed for the allele contrasts, additive genetic model, dominant genetic model and recessive genetic model, respectively. Subgroup analysis was also performed by ethnicity for T869C polymorphism. With respect to T869C polymorphism, no association was found in overall analysis (C vs. T: OR = 1.033, 95% CI = 0.996–1.072). In the subgroup analysis by ethnicity, significantly increased risk was found in Caucasian population (C vs. T: OR = 1.051, 95% CI = 1.018–1.085; CC vs. TT + TC: OR = 1.083, 95% CI = 1.019–1.151), but not in Asian population (C vs. T: OR = 1.054, 95% CI = 0.983–1.130). With respect to C-509T polymorphism, no significant association with breast cancer risk was demonstrated in overall analysis (T vs. C: OR = 0.986, 95% CI = 0.936–1.039). It can be concluded that potentially functional TGF-Β1 T869C polymorphism may play a low penetrance role in breast cancer susceptibility in an ethnicity-specific manner.     

Methylenetetrahydrofolate reductase polymorphisms and breast cancer risk in Chinese population: a meta-analysis of 22 case–control studies

The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk in the Chinese population has been widely reported, but results were inconsistent. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Eligible articles were identified through search of databases including Medline, PubMed, Web of Science, Embase, Chinese Biomedical Literature Database (CBM, Chinese), China National Knowledge Infrastructure (CNKI, Chinese), and Wangfang Database (Chinese). The association between the MTHFR polymorphism and breast cancer risk was conducted using odds ratios (ORs) and 95 % confidence intervals (95 % CIs). Finally, a total of 22 studies with 6,103 cases and 7,913 controls were included in our meta-analysis: 13 studies with 3,273 cases and 4,419 controls for C677T polymorphism and 9 studies with 2,830 cases and 3,494 controls for A1298C polymorphism. With regard to C677T polymorphism, significant association was found with breast cancer risk under three models (T vs. C: OR?=?1.12, 95 % CI?=?1.02–1.23, P?=?0.015; TT vs. CC: OR?=?1.35, 95 % CI?=?1.10–1.67, P?=?0.005; TT vs. CC/CT: OR?=?1.37, 95 % CI?=?1.11–1.70, P?=?0.004). There was no significant association found between A1298C polymorphism and breast cancer risk under all genetic models (C vs. A: OR?=?0.96, 95 % CI?=?0.89–1.03, P?=?0.268; CC vs. AA: OR?=?0.98, 95 % CI?=?0.77–1.26, P?=?0.899; AC vs. AA: OR?=?0.95, 95 % CI?=?0.88–1.02, P?=?0.174; CC vs. AC/AA: OR?=?1.00, 95 % CI?=?0.78–1.28, P?=?0.996, CC/AC vs. AA: OR?=?0.96, 95 % CI?=?0.89–1.02, P?=?0.196). In summary, during this meta-analysis, we found that MTHFR C677T polymorphism was significantly associated with breast cancer risk in the Chinese population. Meanwhile, MTHFR A1298C polymorphism was not associated with breast cancer risk in the Chinese population.     

P53 codon 72 polymorphism contributes to breast cancer risk: a meta-analysis based on 39 case–control studies

P53 is a tumor suppressor gene and plays important roles in the etiology of breast cancer. Studies revealing conflicting results on the role of p53 codon 72 polymorphism (G>C) on breast cancer risk led us to perform a meta-analysis to investigate this relationship. Thirty-nine published studies, including 26,041 breast cancer cases and 29,679 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. The overall results suggested that the variant genotypes were associated with a significantly reduced breast cancer risk (GC vs. GG: OR = 0.91, 95% CI: 0.83–1.00; CC/GC vs. GG: OR = 0.90, 95% CI: 0.82–0.99). In the stratified analyses, significantly decreased risks were also found among European populations (GC vs. GG: OR = 0.89, 95% CI: 0.80–0.99; CC/GC vs. GG: OR = 0.88, 95% CI: 0.80–0.98) and studies with population-based controls (GC vs. GG: OR = 0.88, 95% CI: 0.78–0.98; CC/GC vs. GG: OR = 0.87, 95% CI: 0.78–0.97). The results suggested that p53 codon 72 polymorphism may contribute to susceptibility to breast cancer, especially in Europeans. Additional well-designed large studies were required to validate this association in different populations.     

Alcohol and endometrial cancer risk: a case–control study and a meta-analysis

To evaluate the association between alcohol consumption and endometrial cancer risk, we analyzed data from a hospital-based case–control study, conducted in Italy between 1992 and 2006, on 454 endometrial cancer cases and 908 controls, and performed a meta-analysis updated to October 2009. Compared to never alcohol drinkers, the odds ratio was 1.03 (95% confidence interval, CI, 0.76–1.41) for ≤7, 1.27 (95% CI 0.86–1.87) for 8–14, and 1.19 (95% CI 0.80–1.77) for ≥15 drinks/week, with no trend in risk. No association emerged for wine, beer, and spirit consumption analyzed separately. The meta-analysis included 20 case–control and seven cohort studies, for a total of 13,120 cases. Compared to non/low drinkers, the pooled relative risks for drinkers were 0.90 (95% CI 0.80–1.01) for case–control studies, 1.01 (95% CI 0.90–1.14) for cohort studies, and 0.95 (95% CI 0.88–1.03) overall, with no heterogeneity between study design (p = 0.156). The overall estimate for heavy versus non/low drinkers was 1.12 (95% CI 0.87–1.45). The results were consistent according to selected study characteristics, including geographic area, definition of alcohol drinkers, and type of controls in case–control studies. Our findings provide evidence that alcohol drinking is not associated with endometrial cancer risk, although a weak positive association for very high drinkers cannot be excluded.     

Family history of cancer and the risk of cancer: a network of case–control studies

BackgroundThe risk of many cancers is higher in subjects with a family history (FH) of cancer at a concordant site. However, few studies investigated FH of cancer at discordant sites.Patients and methodsThis study is based on a network of Italian and Swiss case–control studies on 13 cancer sites conducted between 1991 and 2009, and including more than 12 000 cases and 11 000 controls. We collected information on history of any cancer in first degree relatives, and age at diagnosis. Odds ratios (ORs) for FH were calculated by multiple logistic regression models, adjusted for major confounding factors.ResultsAll sites showed an excess risk in relation to FH of cancer at the same site. Increased risks were also found for oral and pharyngeal cancer and FH of laryngeal cancer (OR = 3.3), esophageal cancer and FH of oral and pharyngeal cancer (OR = 4.1), breast cancer and FH of colorectal cancer (OR = 1.5) and of hemolymphopoietic cancers (OR = 1.7), ovarian cancer and FH of breast cancer (OR = 2.3), and prostate cancer and FH of bladder cancer (OR = 3.4). For most cancer sites, the association with FH was stronger when the proband was affected at age <60 years.ConclusionsOur results point to several potential cancer syndromes that appear among close relatives and may indicate the presence of genetic factors influencing multiple cancer sites.     

Levels of insulin-like growth factor during pregnancy and maternal cancer risk: a nested case–control study

Previous studies have suggested that pregnancy measures of insulin-like growth factors (IGFs) may be related to breast cancer risk in mothers. IGFs may also be important in cervical cancer etiology. We conducted a nested case–control study (69 breast cancer cases, 151 cervical cancer cases, 443 controls) among mothers of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Over 70% of blood samples was taken prior to 15 weeks’ gestation; the remainder before 30 weeks. Logistic regression, controlling for maternal age, gestational age, and sample type (plasma/serum) was used to model the association between IGFs and maternal cancer risk. Neither IGF-I nor IGF-II were associated with breast or cervical cancer. IGF-binding protein (BP)-3 was not related to breast cancer, but there was a suggestion that women in the highest compared to lowest quartile of IGFBP-3 had reduced risk of cervical cancer, OR 0.43 (95% CI 0.21–0.86). In conclusion, the importance of IGFs measured in pregnancy and later breast and cervical cancer remains unclear, though IGFBP-3 may be a marker of lowered risk.     

Citrus fruit and cancer risk in a network of case–control studies

Background

Citrus fruit has shown a favorable effect against various cancers. To better understand their role in cancer risk, we analyzed data from a series of case–control studies conducted in Italy and Switzerland.

Patients and methods

The studies included 955 patients with oral and pharyngeal cancer, 395 with esophageal, 999 with stomach, 3,634 with large bowel, 527 with laryngeal, 2,900 with breast, 454 with endometrial, 1,031 with ovarian, 1,294 with prostate, and 767 with renal cell cancer. All cancers were incident and histologically confirmed. Controls were admitted to the same network of hospitals for acute, nonneoplastic conditions. Odds ratios (OR) were estimated by multiple logistic regression models, including terms for major identified confounding factors for each cancer site, and energy intake.

Results

The ORs for the highest versus lowest category of citrus fruit consumption were 0.47 (95% confidence interval, CI, 0.36–0.61) for oral and pharyngeal, 0.42 (95% CI, 0.25–0.70) for esophageal, 0.69 (95% CI, 0.52–0.92) for stomach, 0.82 (95% CI, 0.72–0.93) for colorectal, and 0.55 (95% CI, 0.37–0.83) for laryngeal cancer. No consistent association was found with breast, endometrial, ovarian, prostate, and renal cell cancer.

Conclusions

Our findings indicate that citrus fruit has a protective role against cancers of the digestive and upper respiratory tract.     

Dietary folates and cancer risk in a network of case–control studies

BackgroundFolate deficiency leads to DNA damage and inadequate repair, caused by a decreased synthesis of thymidylate and purines. We analyzed the relationship between dietary folate intake and the risk of several cancers.Patients and methodsThe study is based on a network of case–control studies conducted in Italy and Switzerland in 1991–2009. The odds ratios (ORs) for dietary folate intake were estimated by multiple logistic regression models, adjusted for major identified confounding factors.ResultsFor a few cancer sites, we found a significant inverse relation, with ORs for an increment of 100 μg/day of dietary folate of 0.65 for oropharyngeal (1467 cases), 0.58 for esophageal (505 cases), 0.83 for colorectal (2390 cases), 0.72 for pancreatic (326 cases), 0.67 for laryngeal (851 cases) and 0.87 for breast (3034 cases) cancers. The risk estimates were below unity, although not significantly, for cancers of the endometrium (OR = 0.87, 454 cases), ovary (OR = 0.86, 1031 cases), prostate (OR = 0.91, 1468 cases) and kidney (OR = 0.88, 767 cases), and was 1.00 for stomach cancer (230 cases). No material heterogeneity was found in strata of sex, age, smoking and alcohol drinking.ConclusionsOur data support a real inverse association of dietary folate intake with the risk of several common cancers.     

Lack of significant association between TGF-β1 -590C/T polymorphism and breast cancer risk: a meta-analysis

Transforming growth factor β1 (TGF-β1) is a cytokine that plays an important role in the control of cell proliferation and differentiation in breast cancer. The -509C/T polymorphism in the TGF-β1 gene has been implicated in breast cancer risk. However, studies on the association between this polymorphism and breast cancer risk have produced conflicting results. To derive a more precise estimation of the relationship, a meta-analysis of the -509C/T polymorphism (5,825 cases and 7,953 controls) from seven published case–control studies was performed. Our analysis suggests that -509C/T has no association with breast cancer risk when using either dominant [odds ratio (OR) = 1.01, 95% confidence intervals (CI): 0.82–1.24], or recessive models (OR = 0.91, 95% CI: 0.66–1.27), or other genetic models to analyze the data. In ethnic subgroups analysis, -509C/T also did not appear to be a risk factor for breast cancer. However, larger scale primary studies are still required to further evaluate the interaction of TGF-β1 -509C/T polymorphism and breast cancer risk in specific populations.     

Consumption of different types of meat and the risk of renal cancer: meta-analysis of case–control studies

Background Kidney cancers account for almost 2% of all cancers worldwide, with 150,000 new cases and 78,000 deaths from the disease occurring annually. An increase in the incidence of kidney neoplasm in western countries was noticed in the past few years. Between 1988 and 1992, the incidence of renal cancer per 100,000 person-year among males in USA, Norway, and France was 34.1, 9.00, and 16.10, respectively. Among females in the same countries, it was 5.70, 5.00, and 7.30, respectively. Although several individual case–control studies examined the association of meat intake and renal cancer risk, the results were inconsistent because of the insufficient statistical power of the individual studies. Therefore, the following meta-analysis was designed to help in clarifying the association. Methods Electronic search of MEDLINE, OVID, and PUBMED databases which have articles published between (1966 and 2006) was conducted to select studies for this meta-analysis. Statistical analysis Fixed and random-effects meta-analytical techniques were used to estimate the overall association between meat consumption and kidney cancer. Results Thirteen case–control studies were found. This meta-analysis supported a positive relationship between meat consumption and risk of renal cancer. Summary results indicated that there was from 20% to 22% higher risk of renal cancer among those in the highest relative to the lowest category of poultry and processed meat consumption. Consumption of all meat and red meat was associated with 27% and 30% higher risk, respectively. The increased risks were statistically significant. Conclusions Increased consumption of all meat, red meat, poultry, and processed meat is associated with an increase risk of kidney cancer. Reduction of meat consumption is an important approach to decreasing the incidence of kidney cancer in the general population. An erratum to this article is available at .     

Obesity and risk of malignant melanoma: A meta-analysis of cohort and case–control studies

Although obesity is an established risk factor for several cancer types, its possible role in the aetiology of malignant melanoma remains unclear. This meta-analysis aims to examine the association between obesity and melanoma risk, exploring any tentative gender-specific associations. After the identification of eligible studies, we estimated pooled effect estimates (odds ratios and relative risks), undertook a meta-regression analysis and analysed separately risk of malignant melanoma among males and females in relation to body mass index (BMI) and body surface area (BSA). Out of the 21 eligible articles, 11 used a case–control design encompassing 4460 cases/6342 controls; 10 used a cohort design whose total size comprised 7895 incident cases/6,368,671 subjects. Among males, the pooled effect estimate was 1.31 (95% confidence interval (CI): 1.18–1.45) for overweight and 1.31 (95% CI: 1.19–1.44) for obese. Meta-regression revealed no significant slope, most probably due to the underlying plateau in effect estimates. Among females, no significant association was documented; the pooled effect estimate for overweight and obese subjects was 0.98 (95% CI: 0.92–1.05) and 0.99 (95% CI: 0.83–1.18), respectively. Noticeably, there was evidence for confounding between sunlight exposure and obesity in females. All results were reproducible upon analyses on BSA. In conclusion, overweight and obesity are associated with increased risk of malignant melanoma among males. Meticulous assessment of sunlight exposure is needed especially in women, since self limited public sun exposure may be prevalent among overweight or obese females. Higher-order associations between BMI and melanoma risk should be addressed and examined by the future studies.     

The association between the APE1 Asp148Glu polymorphism and breast cancer susceptibility: a meta-analysis based on case–control studies

Published data regarding the association between the APE1 Asp148Glu polymorphism and breast cancer susceptibility showed inconclusive results. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. We systematically searched PubMed, Embase, Elsevier, and Springer for relevant articles published before December 10. 2013. The strength of association between APE1 Asp148Glu polymorphism and breast cancer susceptibility was assessed by odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) using the software Stata (version 10.0). A total of 7 case–control studies including 3,460 cases and 3,909 controls were included for analysis. Overall, no significant associations were found between the APE1 Asp148Glu polymorphism and breast cancer susceptibility for GG vs TT (OR?=?1.00, 95 % CI?=?0.87–1.14); TG vs TT (OR?=?1.06, 95 % CI?=?0.95–1.18); the dominant model GG?+?TG vs TT (OR?=?1.04, 95 % CI?=?0.94–1.16) and the recessive model GG vs TG?+?TT (OR?=?0.99, 95 % CI?=?0.88–1.11). In subgroup analysis, a significant association was found for TG vs TT in Asian subgroup (OR?=?1.17, 95 % CI?=?1.00?~?1.36) and in population-based subgroup (OR?=?1.18, 95 % CI?=?1.00?~?1.38). This meta-analysis suggested that the APE1 Asp148Glu polymorphism was a risk factor for breast cancer susceptibility among Asian population.     

Circulating leptin levels and risk of colorectal cancer and adenoma: a case–control study and meta-analysis

Purpose

Equivocal results regarding the role of leptin in colorectal cancer (CRC) and adenoma (CRA) have been reported. A case–control study investigating the association of leptin with CRC risk and clinicopathological characteristics along with meta-analysis of published data on both CRC and CRA were conducted.

Methods

Pubmed and Embase were searched for the meta-analysis, comprising 28 case–control studies amounting 3,614 CRC and 1,215 CRA cases, along with 5,220 controls. Meticulous contact with the authors of individual studies was undertaken for the provision of additional data. Pooling of standardized mean differences (SMD), relative risks (RR) and 95 % CI (random effects models), subgroup, sensitivity, and meta-regression analyses were conducted.

Results

The meta-analysis suggested positive association of serum leptin with CRA (RR, 95 % CI 1.35, 1.03 to +1.76), but not CRC either at the pooled analysis on SMDs or RRs (SMD, 95 % CI 0.18, ?0.04 to +0.40; RR, 95 % CI 1.04, 0.65 to +1.65). Significant heterogeneity between studies on CRC as well as between studies on CRA providing SMD was noted. Subgroup, meta-regression and sensitivity analyses highlighted potential methodology-, design-, size- and quality-related effect modifiers.

Conclusions

Meta-analysis of current evidence suggests positive association of serum leptin with CRA but not with CRC risk. Given the case–control nature of available studies, the limited number of studies on serum leptin and CRA, and the heterogeneity of CRC studies, carefully designed, prospective studies preferably reporting RRs adjusted for a variety of confounders may be warranted.     

Diabetes and risk of pancreatic cancer: a pooled analysis of three large case–control studies

Racial differences in diabetes-associated pancreatic cancer (PC) and the interaction of diabetes with other risk factors are not well established. We determined the association between diabetes and risk of PC in 2,192 cases and 5,113 controls in three large case–control studies conducted at the National Cancer Institute, the University of California San Francisco, and the M.D. Anderson Cancer Center. In multivariable analyses, diabetes was associated with a 1.8-fold risk of PC [95% confidence interval (CI) = 1.5–2.1]. Risk estimates decreased with increasing years with diabetes (≤2 years OR = 2.9, 95% CI = 2.1–3.9; 3–5 years OR = 1.9, 95% CI = 1.3–2.6; 6–10 years OR = 1.6, 95% CI = 1.2–2.3; 11–15 years OR = 1.3, 95% CI = 0.9–2.0; > 15 years OR = 1.4, 95% CI = 1.0–2.0 (p for trend < 0.0001). Among diabetics, risk was higher in insulin ever users compared with nonusers (OR = 2.2, 95% CI = 1.6–3.7) and was restricted to insulin use of ≤3 years (OR = 2.4). Insulin use of >10 years was associated with a reduced risk of pancreatic cancer (OR = 0.5, 95% CI = 0.3–0.9; p for trend < 0.0001). Hispanic men and Asians had a higher risk of diabetes-associated PC than did whites and blacks, but the differences were not statistically significant. No significant interaction between diabetes and cigarette smoking, alcohol consumption and body mass index was observed. Although reverse causation may explain the association between diabetes diagnosed in close temporal proximity to PC, our results show that long-term diabetes, even though risk diminishes over time, remains a risk factor for PC independent of obesity and smoking.     

Occupational exposure to pesticides and risk of hematopoietic cancers: meta-analysis of case–control studies

Objective In this study we conducted a meta-analysis of 13 case–control studies that examined the occurrence of hematopoietic cancers in pesticide related occupations in order to undertake a qualitative and quantitative evaluation of a possible relationship. Methods Pubmed databases were searched for case–control studies published between 1990 and 2005 investigating the relation between hematopoietic cancers and occupational exposure to pesticides. Fixed and random effect meta-analysis models were used depending on the presence of heterogeneity between studies. Results The overall meta-odds ratio obtained after pooling 44 ORs from 13 studies was 1.3 (95% CI: 1.3–1.5). We realized stratified analysis on three different types of hematopoietic cancers (non-Hodgkin lymphoma (NHL), leukemia and multiple myeloma). A significant increased risk of NHL was found (OR = 1.35; 95% CI = 1.2–1.5). Moreover, increased risks of Leukemia (OR = 1.35; 95% CI = 0.9–2) and multiple myeloma (OR = 1.16; 95% CI = 0.99–1.36) were also detected but these results were not statistically significant. Significant heterogeneity existed among the different studies and a publication bias was detected. Therefore, a meta-regression was carried out. Our results showed that a long period of exposure (more than 10 years) provided an increase in the risk of all hematopoietic cancers and for NHL by fractions of 2.18 (95% CI = 1.43–3.35) and 1.65 (95% CI = 1.08–2.51), respectively. Conclusions: The overall meta-odds ratio suggests that there is a significantly positive association between occupational exposure to pesticides and all hematopoietic cancers as well as NHL. A major limitation of our meta-analysis is the lack of sufficient data about exposure information and other risk factors for hematopoietic cancer (genetic predisposition, ethnic origin, immunodepression…). In addition, data concerning specific subtypes of hematopoietic cancers are often confusing. Thus, future epidemiological studies should undertake a major effort to assess the identity and the level of pesticides exposure and should control for the most likely potential confounders.