Colorectal Cancer In Females Research Articles

SMAD7 gene polymorphisms and their influence on patients with colorectal cancer

ABSTRACT Colorectal cancer (CRC) is a prevalent malignant tumor, and its pathogenesis is still not fully understood. Studies have shown that SMAD7 gene polymorphisms can affect CRC susceptibility, but the results have been inconsistent and require additional confirmation. Our study aimed to evaluate the effect of SMAD7 variants on the risk of CRC in the Chinese Han population. A total of five single nucleotide polymorphisms (SNPs) in SMAD7 were genotyped among 696 CRC patients and 696 healthy participants using the MassARRAY iPLEX platform. SNPs were evaluated for their associations with CRC using logistic regression analysis under multiple genetic models. The false-positive report probability (FPRP) analysis was used to validate the positive findings. Our study indicated that rs11874392 showed an increased association with CRC risk (odds ratio, 1.31; 95% confidence interval, 1.04–1.67; p = 0.024). Stratified analysis showed that rs11874392 might increase the risk of CRC in females (OR = 1.70, p = 0.028), individuals with smoking (OR = 1.87, p = 0.026), and drinking (OR = 1.38, p = 0.027). The rs11874392 was found to be related to an elevated risk of rectal cancer (OR = 1.73, p = 0.003), but not with colon cancer. FPRP analysis demonstrated that all of these associations were statistically significant (FPRP <0.2). Additionally, rs11874392 was the strongest predictive model for CRC. This study provides evidence that the SMAD7 rs11874392 is related to an increased susceptibility to CRC.

The Risk of Colorectal Polyps after Weight Loss Therapy Versus Obesity: A Propensity-Matched Nationwide Cohort Study.

A fundamental understanding of the impact of bariatric surgery (BRS) on mechanisms of colorectal carcinogenesis is limited. For instance, studies report a reduced risk of colorectal cancer in females but not in males after BRS. We examined whether this sex-specific difference existed at the earlier polyp development stage. This retrospective cohort study included 281,417 adults from the 2012-2020 MarketScan database. We compared polyps rates on colonoscopy in four groups: post- vs. pre-BRS (treatment) to post- vs. pre-severe obesity (SO) diagnosis (control). We focused our main analysis on a propensity-matched sample that yielded a balanced distribution of covariates in our four groups (n = 9680 adults, 21.9% males). We also adjusted for important covariates. Metabolic syndrome parameters improved after bariatric surgery and worsened after severe obesity diagnosis (p < 0.05). The rate of polyps was 46.7% at a median of 0.5 years pre-BRS and 47.9% at a median of 0.6 years pre-SO diagnosis. The polyps rate was 45.4% at a median (range) of 3.2 (1.0-8.5) years post-BRS. Conversely, 53.8% of adults had polyps at 3.0 (1.0-8.6) years post-SO. There was no change in the risk of colorectal polyps in males or females post- vs. pre-BRS. However, the risk of polyps was higher in males (OR = 1.32, 95% CI: 1.02-1.70) and females (OR = 1.29, 95% CI: 1.13-1.47) post- vs. pre-SO. When compared to the control group (SO), the odds ratios for colorectal polyps were lower for males and females after bariatric surgery (OR = 0.63, 95% CI: 0.44-0.90, and OR = 0.79, 95% CI: 0.66-0.96, respectively). Obesity is associated with an increased risk of colorectal polyps, an effect that is ameliorated after bariatric surgery. These data are relevant for studies investigating colorectal carcinogenesis mechanisms.

Colorectal cancer in patients of advanced age is associated with increased incidence of BRAF p.V600E mutation and mismatch repair deficiency.

The highest incidence of colorectal cancer (CRC) is in patients diagnosed at 80 years or older highlighting a need for understanding the clinical and molecular features of these tumors. Methods. In this retrospective cohort study, 544 CRCs underwent next generation sequencing and mismatch repair (MMR) evaluation. Molecular and clinical features were compared between 251 patients with traditional-onset CRC (50-69 years at diagnosis) and 60 with late-onset CRC (>80 years at diagnosis). Late-onset CRC showed a significantly higher rate of right-sided tumors (82% vs 35%), MMR deficiency (35% vs. 8%) and BRAF p.V600E mutations (35% vs. 8%) and a significantly lower rate of stage IV disease (15% vs 28%) and APC mutations (52% vs. 78%). Association of these features with advanced age was supported by stratifying patients into 6 age groups (<40, 40-49, 50-59, 60-69, 70-79 and >80 years). However, the age-related rise in MMR deficient (dMMR) CRC was only seen in the female patients with an incidence of 48% (vs. 10% in the male patient) in the >80y group. In addition, BRAF p.V600E was significantly enriched in MMR deficient CRC of advanced age (67% in late-onset CRC). Categorizing CRC by mutational profiling, late-onset CRC revealed a significantly higher rate of dMMR/BRAF + APC - (18% vs. 2.0%), dMMR/BRAF - APC - (8.3% vs. 1.2%) and MMR proficient (pMMR)/BRAF + APC - (12% vs. 4.0%) as compared to traditional-onset CRC. In summary, there was a higher rate of dMMR and BRAF p.V600E in late-onset CRC, independently or in combination. The higher incidence of dMMR in late-onset CRC in females is most likely predominantly driven by BRAF p.V600E induced hypermethylation. Prospective studies with treatment plans designed specifically for these older patients are warranted to improve their outcomes.

Evaluation of Birth by Cesarean Delivery and Development of Early-Onset Colorectal Cancer

The incidence of early-onset colorectal cancer (CRC), diagnosed younger than 50 years of age, has increased worldwide. Gut dysbiosis throughout the life course is hypothesized as a leading mechanism, yet epidemiologic data are limited. To prospectively examine the association between birth by cesarean delivery and early-onset CRC among offspring. In this population-based, nationwide case-control study in Sweden, adults diagnosed with CRC between 18 and 49 years of age from 1991 to 2017 were identified through the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. Up to 5 general population control individuals without CRC were matched with each case on age, sex, calendar year, and county of residence. Pathology-confirmed end points were linked with the Swedish Medical Birth Register and other national registers. Analyses were conducted from March 2022 through March 2023. Birth by cesarean delivery. The primary outcome was development of early-onset CRC in the overall population and by sex. We identified 564 case patients with incident early-onset CRC (mean [SD] age, 32.9 [6.2] years; 284 [50.4%] male) and 2180 matched controls (mean [SD] age, 32.7 [6.3] years; 1104 [50.6%] male). Compared with vaginal delivery, birth by cesarean delivery was not associated with early-onset CRC in the overall population (adjusted odds ratio [aOR], 1.28; 95% CI, 0.91-1.79) after multivariable adjustment for matching and maternal and pregnancy-related factors. A positive association was found for females (aOR, 1.62; 95% CI, 1.01-2.60), but there was no association for males (aOR, 1.05; 95% CI, 0.64-1.72). In this nationwide, population-based case-control study, birth by cesarean delivery was not associated with early-onset CRC compared with birth by vaginal delivery in the overall population in Sweden. However, females born by cesarean delivery had greater odds of early-onset CRC compared with individuals born through vaginal delivery. This finding suggests that early-life gut dysbiosis may contribute to early-onset CRC in females.

High serum uric acid may associate with the increased risk of colorectal cancer in females: A prospective cohort study.

Elevated serum uric acid (SUA) levels have been previously reported to play a role in multiple types of cancers. However, epidemiological studies evaluating SUA levels and colorectal cancer risk remain sparse. This cohort study included 444 462 participants between the ages of 40 and 69 years from the UK Biobank, followed up from 2006 to 2010. Multivariable adjusted Cox regression models were used to estimate hazard ratios (HRs). During a mean follow-up of 6.6 years, 2033 and 855 cases of colon and rectal cancers, respectively, were diagnosed. The multivariable-adjusted HRs for risks of colon cancer in the lowest uric acid categories (≤3.5mg/dL) compared with the reference groups were 1.31 (95% confidence interval [CI]=0.75-2.29) in males and 1.26 (95%CI=1.03-1.55) in females. The HRs in the highest uric acid groups (>8.4mg/dL) were 1.16 (95%CI=0.83-1.63) in males and 2.00 (95%CI=1.02-3.92) in females. The corresponding HRs of rectal cancer in the lowest uric acid groups compared with the reference group were 2.21 (95%CI=1.15-4.23) in males and 0.98 (95%CI=0.66-1.45) in females. The HRs in the highest uric acid groups were 1.35 (95%CI=0.82-2.23) in males and 3.81 (95%CI=1.38-10.56) in females. In conclusion, SUA showed a U-shaped association with colon cancer risk in both male and female populations. The same pattern was observed in male patients with rectal cancer. However, SUA levels were positively associated with occurrence of rectal cancer in female subjects.

High-fat diet-fed ovariectomized mice are susceptible to accelerated subcutaneous tumor growth potentially through adipose tissue inflammation, local insulin-like growth factor release, and tumor associated macrophages.

Background: The association between obesity and colorectal cancer (CRC) risk has been well established. This relationship appears to be more significant in men than in women, which may be attributable to sex hormones. However, controlled animal studies to substantiate these claims and the mechanisms involved are lacking.Materials and Methods: MC38 murine colon adenocarcinoma cells were injected subcutaneously into high-fat diet (HFD) fed male, female and ovariectomized (OVX) female C57BL/6 mice.Results: HFD increased tumor growth (main effect) that was consistent with metabolic perturbations (P < 0.01). HFD OVX mice exhibited the most significant tumor growth compared to HFD male and female mice (p < 0.05) and this was associated with increased subcutaneous adipose tissue (p < 0.05). Further, the subcutaneous adipose tissue depots within HFD OVX mice exhibited more severe macrophage associated inflammation compared to female (P < 0.01), but not male mice. Conditioned media from subcutaneous adipose tissue of HFD OVX contained higher IGF-1 levels compared to male (P < 0.01), but not female mice. Finally, HFD OVX mice had increased M2-like gene expression in their tumor-associated macrophages (TAMs) compared to female mice (P < 0.01).Conclusions: This work provides evidences suggesting adiposity, adipose specific IGF-1, macrophage associated adipose inflammation, and TAMs as potential mechanisms driving obesity-enhanced CRC in females lacking ovarian hormones.

Gut microbiome is more stable in males than in females during the development of colorectal cancer.

Gut microbial alterations have great potential to predict the development of colorectal cancer (CRC); however, how gut microbes respond to the development of CRC in males and females at the community level is unknown. We aim to investigate the differences of gut microbiota between the male and female. We reanalysed the dataset in a published project from a sex perspective at the community level by characterizing the gut microbiome in patients (including males and females) from three clinical groups representative of the stages of CRC development: healthy, adenoma, and carcinoma. The results indicated that the microbial α-diversity showed no significant difference in the male gut but had decreased significantly in the female gut with the development of CRC. In males, a significant difference in the microbial β-diversity was only observed between the healthy and carcinoma subgroups. However, significant community deviations were detected with the development of CRC in females. The microbial community assembly processes changed from deterministic to stochastic in males, whereas they became increasingly deterministic in females with the development of CRC. Moreover microbial co-occurrence associations tended to be more complicated in males; rare species were enriched in the co-occurrence network of the male gut, whereas key species loss was observed in the co-occurrence network of the female gut. The microbial communities in the male gut were more stable than those in the female gut, and microbial community assembly in the gut was sex dependent with the development of CRC. Our study suggests that sexual dimorphism needs to be considered to better predict the risk of CRC based on microbial shifts. To the best of our knowledge, this is the first report showing how gut microbes respond to the development of CRC in males and females at the community scale.

Association of MDM4 Gene rs4245739 Polymorphism with the Risk and Clinical Characteristics of Colorectal Cancer in a Chinese Han Population.

BackgroundStudies show that MDM4 may play a pivotal role in colorectal cancer (CRC). Recently, a host of studies suggest that MDM4 gene rs4245739 polymorphism may modify the risk of different cancers.MethodsIn this study, we were interested whether MDM4 gene rs4245739 polymorphism correlated with the risk and clinical characteristics of CRC. Logistic regression was adopted to estimate the association of rs4245739 polymorphism and CRC risk.ResultsWe enrolled 444 CRC patients and 530 controls and found MDM4 gene rs4245739 polymorphism may decrease the risk of CRC. Stratified analyses uncovered that this variant was connected to a less risk of CRC in females, non-drinkers, non-smokers, and people under 60 years old. Additionally, rs4245739 polymorphism was related to TNM staging, pathological type, tumor size, and location of CRC. Furthermore, this polymorphism was significantly linked with the survival of CRC.ConclusionTotally, this study suggests that MDM4 rs4245739 polymorphism is linked with the risk and clinical characteristics of CRC.

The association between hypertension and colorectal cancer: a meta-analysis of observational studies.

The relationship between hypertension and risk of colorectal cancer (CRC) is unclear. This meta-analysis aims to explore the association between them. Six databases were searched for studies published before August 2019. The pooled relative risk (RR) and 95% confidence intervals (CIs) were calculated to estimate the association between the hypertension and CRC risk. A total of 2841 potentially relevant articles were obtained, and 25 studies with a pooled 1.95 million participants were finally included in the meta-analysis. These results suggested a positive association between hypertension and risk of CRC with a pooled RR of 1.15 (95% CI: 1.08, 1.23). Male patients with hypertension had a 13% (95% CI: 1.06, 1.20) increased risk of CRC. The risk of colon cancer and rectal cancer in male patients was 1.17 (95% CI: 1.01, 1.36) and 1.35 (95% CI: 1.04, 1.74), respectively, while no association between hypertension and the risk of CRC in females was elucidated. This meta-analysis demonstrated that a positive association between hypertension and CRC exists, with male patients having a higher risk of developing CRC than female patients.

Prevalence and Risk Factors of Gastric and Colorectal Cancer after Cholecystectomy.

BackgroundPrevious studies on the relationship between gastrointestinal (GI) cancer and cholecystectomy remain inconclusive. We aimed to evaluate this relationship, albeit particularly between cholecystectomy and gastric cancer or colorectal cancer (CRC), and the risk factors of cancer among individuals who have undergone cholecystectomy in Korea.MethodsIn total, 4,222 patients who underwent laparoscopic or open cholecystectomy at our institution between January 2006 and December 2013 were included. Patients who underwent cholecystectomy for gallbladder cancer or were undergoing surgery for GI, hepatic, or pancreatobiliary cancers were excluded, as were those who developed stomach cancer or CRC within a year of their cholecystectomy. The included patients were followed until July 20, 2020. The standardized incidence ratio (SIR) was used to calculate the relative risk of GI cancer in cholecystectomy patients.ResultsThe median patient age (n = 3,588) at the time of cholecystectomy was 54.0 (range, 19–95) years, and the male-to-female ratio was 1:1.04. The median follow-up period after cholecystectomy was 15.0 (range, 0–146) months. We found a 108% greater risk of CRC (SIR, 2.08; 95% confidence interval [CI], 1.28–3.17) and 154% increased risk of CRC in females (SIR, 2.54; 95% CI, 1.16–4.84). Based on multivariate analysis, an age of > 60 years was a significant risk factor for GI cancer in cholecystectomy patients.ConclusionCholecystectomy may increase risk of CRC, especially in females. Age was considered a risk factor of GI cancers in patients with history of cholecystectomy.

Sex-dependent regulation of estrogen receptor beta in human colorectal cancer tissue and its relationship with clock genes and VEGF-A expression.

The incidence of colorectal cancer (CRC) shows a sex-dependent difference in humans. The aim of this study was to analyze estrogen receptor beta mRNA (ERbeta) expression in patients with CRC with respect to their gender and clinicopathological features. Since cancer progression is accompanied by tumor vascularization, VEGF-A (vascular endothelial growth factor A) transcription was analyzed along with ERbeta mRNA. ERbeta mRNA was also correlated with the expression of clock genes, which are known to influence the cell cycle. ERbeta mRNA expression in females with CRC showed an inverse association with increasing tumor staging that was not observed in males. Lower levels of ERbeta mRNA were observed in females with a higher clinical stage compared with those with earlier-stage tumors. ERbeta mRNA expression showed a significant positive correlation with mRNA of clock genes period 2 and cryptochrome 2 in healthy but not in cancerous tissue in males. Expression of VEGF-A mRNA showed a negative correlation with ERbeta mRNA after splitting of the cohort according to gender and nodus involvement. We propose that gender differences in ERbeta mRNA expression in tumors during the early stages of CRC can partially explain the lower occurrence of CRC in females compared with males.

Association of CD44 gene rs187115 polymorphism with colorectal cancer risk and prognosis in Chinese Han population: a case-control study.

The cell surface adhesion receptor CD44 reportedly affects the development and progression of cancers. Moreover, CD44 gene rs187115 polymorphism appears to be genetic determinant of cancer susceptibility. We investigated whether CD44 rs187115 polymorphism is associated with colorectal cancer (CRC) risk and prognosis. We enrolled 669 CRC cases and 826 controls in this three-center case-control study in a Chinese Han population. All individuals were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Cross-over analysis, multivariate logistic regression, Kaplan-Meier method, and Cox regression analysis were used for analysis. In this study, CD44 rs187115 polymorphism was associated with increased risk for CRC. Stratified analyses revealed that CD44 rs187115 polymorphism was correlated with increased risk for CRC in females, drinkers, smokers, and those aged ≥ 60 years. In addition, rs187115 polymorphism was significantly associated with TNM III+IV stage, lymph node metastasis and tumor size in CRC patients. Combined effects of CD44 rs187115 polymorphism (GG/AG vs. AA) and environmental factors (smoking and drinking) further increased the risk of CRC. GG genotype carriers showed poorer overall survival than AA genotype carriers. Cox regression analysis showed that drinking, CD44 rs187115 polymorphism, and TNM stage were independent prognostic factors affecting CRC. These findings show that CD44 rs187115 polymorphism may be a potential biomarker predictive of CRC susceptibility and prognosis.

Mo1617 - Epidemiology of Colorectal Cancer in Females with Breast Cancer in the United States Between 2012 and 2017: A Population Based National Study

Mo1617 - Epidemiology of Colorectal Cancer in Females with Breast Cancer in the United States Between 2012 and 2017: A Population Based National Study

Association between shiftwork and the risk of colorectal cancer in females: a population-based case–control study

ObjectiveResearch indicates that shiftwork may be associated with increased risks of adverse health outcomes, including some cancers. However, the evidence of an association between shiftwork and colorectal cancer risk is...

Gender-associated genomic differences in colorectal cancer: clinical insight from feminization of male cancer cells.

Gender-related differences in colorectal cancer (CRC) are not fully understood. Recent studies have shown that CRC arising in females are significantly associated with CpG island methylator phenotype (CIMP-high). Using array comparative genomic hybridization, we analyzed a cohort of 116 CRCs (57 males, 59 females) for chromosomal copy number aberrations (CNA) and found that CRC in females had significantly higher numbers of gains involving chromosome arms 1q21.2–q21.3, 4q13.2, 6p21.1 and 16p11.2 and copy number losses of chromosome arm 11q25 compared to males. Interestingly, a subset of male CRCs (46%) exhibited a “feminization” phenomenon in the form of gains of X chromosomes (or an arm of X) and/or losses of the Y chromosome. Feminization of cancer cells was significantly associated with microsatellite-stable CRCs (p-value 0.003) and wild-type BRAF gene status (p-value 0.009). No significant association with other clinicopathological parameters was identified including disease-free survival. In summary, our data show that some CNAs in CRC may be gender specific and that male cancers characterized by feminization may constitute a specific subset of CRCs that warrants further investigation.

Cancer incidence in California farm workers, 1988-2010.

Farmers and farm workers have previously been found to experience decreased risk of some causes of death but elevated risks of certain types of cancer. A previous report on cancer incidence in a farm worker labor union between 1987 and 1997 found increased leukemia, brain, stomach, and uterine cervix cancer rates in this working population. A roster of farm workers was created and electronically linked to the database of the California Cancer Registry. Proportionate cancer incidence (PCIR), stage, and age at diagnosis and histological subtypes of cancer were compared between the United Farm Workers (UFW) members and the Hispanic population of California as well as to the non-Hispanic whites (NHW). In this population of 139,000 farm workers in California, more than 3,600 cancer diagnoses were recorded between 1988 and 2010. Proportionately more cancer was noted in the UFW than among California NHW for kidney and renal pelvis cancer (PCIR = 1.60), liver (PCIR = 4.24), prostate (PCIR = 1.13), and uterine cervix cancer (PCIR = 2.08). Proportionately less breast (PCIR = 0.85), lung (PCIR = 0.75), skin melanoma (PCIR = 0.18), and urinary bladder cancer (PCIR = 0.59) was found. Stage at diagnosis was more advanced in the farm workers for several cancer sites, although, not for colorectal cancer. These farm workers experience proportionally more prostate, kidney and renal pelvis, brain, liver, stomach, cervix and leukemia and less breast, melanoma, and colorectal cancer than reference populations. For many sites, cancer is not diagnosed as early in the farm workers as in the comparison groups, except for colorectal cancer in females and melanoma in males.

Association of polymorphisms in microRNA-binding sites and colorectal cancer in an Iranian population

MicroRNAs (miRNAs) are agents of post-transcriptional gene expression, and they can affect many functions of an individual cell or tissue from extracellular matrix production to inflammatory processes and tumor development. We aimed to determine the possible role of miRNA-binding site polymorphisms located in five cancer-related genes: IL-16, CDKN2A (p16), RAF1, PTGER4, and ITGB4 in colorectal cancer (CRC) risk modification in an Iranian population. This study was performed on 643 individuals (249 CRC cases and 394 healthy controls). We selected five cancer-related genes (IL-16, CDKN2A (p16), RAF1, PTGER4, and ITGB4) and investigated the genotypes of the 3' untranslated region miRNA-binding site polymorphisms in these genes in our study population. The restriction fragment length polymorphism results were confirmed by a direct sequencing method. We found a statistically significant difference between the rs1131445 polymorphism of the IL-16 gene and CRC. The frequencies of the genotypes TT, CT, and CC in controls were 51%, 40.4%, and 8.6%, respectively, and in cases were 41.4%, 44.1%, and 14.5%, respectively, which shows a significant association between the CC genotype of the rs1131445 polymorphism and CRC (P = 0.004). The frequency of the C allele in the CRC group was higher than in the controls, and the C allele of the rs1131445 polymorphism was found to be in association with CRC (P = 0.009). These associations remained significant after Bonferroni's correction for multiple testing. We found that the AA genotype of the rs743554 polymorphism in the ITGB4 gene and the T allele of the rs1051208 polymorphism of the RAF1 gene were associated with the risk of CRC in females; however, after Bonferroni's correction we found that they were non-significant. Finally, we can conclude that a significant relationship exists between the miRNA-binding site polymorphism of the IL-16 gene and CRC risk in the Iranian population.

NAT2 fast acetylator genotype and MGMT promoter methylation may contribute to gender difference in K‐RAS mutation occurrence in Taiwanese colorectal cancer

A recent study conducted by our group showed that the NAT2 fast acetylator genotype is associated with an increasing risk for the development of colorectal cancer (CRC), especially for females. We therefore examined whether a higher risk of CRC in females with the NAT2 fast acetylator genotype was associated with the occurrence of K-RAS mutation, and to further verify whether MGMT promoter methylation was linked to the occurrence of K-RAS mutation in patients with the NAT2 fast acetylator genotype. Herein, 151 CRC cases were examined for NAT2 genetic polymorphisms and MGMT promoter methylation by PCR-RFLP and methylation-specific PCR (MSP). The results of this study show that the NAT2 fast acetylator genotype is associated with the occurrence of K-RAS mutation in female cases (OR = 4.820, 95% CI = 1.113-20.873), but not associated with MGMT promoter methylation. Surprisingly, MGMT promoter methylation significantly deepens the impact of NAT2 fast acetylation on K-RAS mutation in the female cases (OR = 5.129, 95% CI = 1.092-24.105). In conclusion, Taiwanese women with the NAT2 fast acetylator genotype may exhibit a higher risk of CRC with increased occurrence of K-RAS mutation. Detection of NAT2 genotypes and MGMT promoter methylation may be useful in the risk assessment for CRC in Taiwanese women.

Metabolic syndrome and cancer risk

Objective The purpose of this population-based study is to explore for the first time the link between metabolic syndrome and cancer risk using information from the health information system of the Cancer Registry. Methods Referring to all pharmaceutical prescriptions between 1 January 1999 and 31 December 2005, coded with the Anatomical Therapeutic Chemical classification, all subjects aged 40 and over resident in Milan, which were simultaneously prescribed with antihypertensive, hypolypemic and hypoglycaemic drugs, were considered affected by metabolic syndrome. New cancer cases among cohort subjects were identified trough the local Cancer Registry and standardised incidence ratios (and corresponding 95% exact confidence intervals) were computed. Results Overall 16,677 subjects were identified corresponding to 45,828 person-years; among them 823 incidents cancers occurred. Significantly increased risks for pancreatic cancer in males - SIR 178 (114–266) - and colorectal cancer in females - SIR 133 (101–170) - were observed. Non-significantly increased risks were also observed in women for liver, gallbladder and biliary tract, breast and endometrial cancers. Conclusions Our study suggests that the risk for several cancers increases in subjects affected by metabolic syndrome. The pharmacological control of the syndrome seems to be inadequate for reducing cancer risk, even though both a high competitive mortality effect and short duration of follow up have to be considered.

Chemoprevention for colon cancer: New opportunities, fact or fiction?

Colorectal cancer (CRC) is still a disease with a high incidence and mortality. Prevention of (pre-) cancerous lesions of CRC by endoscopic screening is promising, but costs are high and identification of high-risk populations is difficult. Since screening both average-risk and high-risk populations for CRC has its logistic and financial limitations, new primary prevention strategies are sought. Substantial evidence has shown that non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors can reduce the incidence and mortality of CRC. However, long-term use of NSAIDs is associated with substantial gastrointestinal toxicity and may cause an exacerbation in IBD patients. Selective COX-2 inhibitors, with a better toxicity profile and no flare-up in IBD disease activity, are therefore attractive candidates for prevention. Chemoprevention with low-dose aspirin can be considered for individuals carrying a high risk for CRC. Folate supplementation is beneficial to the folate-depleted patients, since significant risk reductions for CRC are reported. Moreover, it might be applicable to the general population because it is safe, inexpensive and protects against vascular diseases. In line with drugs beneficial for multiple disease entities, statins have recently been proposed to reduce CRC risk. Ursodeoxycholic acid has been shown to decrease the incidence of colonic dysplasia in patients with ulcerative colitis and PSC and possibly reduces recurrence rates of polyps in general. Unfortunately, prospective randomized trials, in both high-risk and general population, are not available and the evidence is still controversial. Furthermore, cumulative epidemiological and observational data suggest the potential role of hormones as a chemoprotective agent. An increase in CRC in females with an early menopause, as well as a decrease of CRC in women with hormone replacement therapy justify further research into this issue. In IBD patients, both the severity and duration of the inflammation are the most evident risk factors for the development of dysplasia and subsequently cancer. Remission of inflammation, clinically, endoscopically and histologically, in IBD is the major goal. Long-term use of 5-aminosalicylates (5-ASA) has been shown to decrease the incidence of CRC and may hold the best promise as a chemoprotective agent in IBD. In parallel with primary prevention strategies in vascular medicine, the aim might be to postpone adenoma formation, for instance for 10 years, thereby achieving a significant risk reduction for CRC. In current practice, folate supplementation along with low-dose aspirin use in high-risk patients may be most attractive candidates, while future studies will have to clarify the role of these and other chemoprotective agents.