Increasing evidence from animal and in vitro studies indicates that n-3 fatty acids, especially the long-chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, present in fatty fish and fish oils inhibit carcinogenesis. The epidemiologic data on the association between fish consumption, as a surrogate marker for n-3 fatty acid intake, and cancer risk are, however, somewhat less consistent. This review highlights current knowledge of the potential mechanisms of the anticarcinogenic actions of n-3 fatty acids. Moreover, a possible explanation of why some epidemiologic studies failed to find an association between n-3 fatty acid intake and cancer risk is provided. Several molecular mechanisms whereby n-3 fatty acids may modify the carcinogenic process have been proposed. These include suppression of arachidonic acid-derived eicosanoid biosynthesis; influences on transcription factor activity, gene expression, and signal transduction pathways; alteration of estrogen metabolism; increased or decreased production of free radicals and reactive oxygen species; and mechanisms involving insulin sensitivity and membrane fluidity. Further studies are needed to evaluate and verify these mechanisms in humans to gain more understanding of the effects of n-3 fatty acid intake on cancer risk.

Our findings strongly support a relationship between diabetes and increased risk of colon and rectal cancer in both women and men.

Diabetes mellitus has been associated with an increased risk of several types of cancers, but its relationship with breast cancer remains unclear. We conducted a meta-analysis of case-control and cohort studies to assess the evidence regarding the association between diabetes and risk of breast cancer. Studies were identified by searching MEDLINE (1966( -February 2007 and the references of retrieved articles. We identified 20 studies (5 case-control and 15 cohort studies) that reported relative risk (RR) estimates (odds ratio, rate ratio/hazard ratio, or standardized incidence ratio) with 95% confidence intervals (CIs) for the relation between diabetes (largely Type II diabetes) and breast cancer incidence. Summary RRs were calculated using a random-effects model. Analysis of all 20 studies showed that women with (versus without) diabetes had a statistically significant 20% increased risk of breast cancer (RR, 1.20; 95% CI, 1.12-1.28). The summary estimates were similar for case-control studies (RR, 1.18; 95% CI, 1.05-1.32) and cohort studies (RR, 1.20; 95% CI, 1.11-1.30). Meta-analysis of 5 cohort studies on diabetes and mortality from breast cancer yielded a summary RR of 1.24 (95% CI, 0.95-1.62) for women with (versus without) diabetes. Findings from this meta-analysis indicate that diabetes is associated with an increased risk of breast cancer. ' 2007 Wiley-Liss, Inc.Key words: breast cancer; epidemiology; diabetes; meta-analysis; systematic review Diabetes mellitus is a serious and growing health problem worldwide.1 Type 2 diabetes accounts for 90-95% of all diagnosed cases of diabetes 2 and is characterized by insulin resistance and hyperinsulinemia in the early phases of the disease.3 It has been hypothesized that hyperinsulinemia may increase the risk of breast cancer through direct effects on breast tissue or indirectly by increasing circulating concentrations of estrogens, testosterone and insulin-like growth factors.4,5 Thus, Type 2 diabetes may confer an excess risk of breast cancer. Diabetes has been related to an elevated risk of several cancers. Meta-analyses have indicated that diabetes is associated with a 1.2-fold increased risk of bladder cancer, 6 1.3-fold increased risk of colorectal cancer, 7 1.7-fold increased risk of pancreatic cancer 8 and 2.5-fold increased risk of hepatocellular carcinoma.9 Wolf et al. combined the results of 4 case-control and 6 cohort studies and found that diabetes was associated with a 13 and 25% increased risk of breast cancer in case-control and cohort studies, respectively. 10The purpose of the present study was to summarize all available evidence from case-control and cohort studies on the relationship between diabetes and breast cancer incidence and mortality following the meta-analysis of observational studies in epidemiology (MOOSE) guidelines for meta-analyses of observational studies. 11This meta-analysis includes a total of 23 studies, thus providing more precise risk estimates than the previous analysis by Wolf et al. 10 that was based on only 10 studie...

The association between obesity and colon and rectal cancer risk varies by sex and cancer site.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1 . In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P <5×10 −8 , bringing the number of known independent signals for CRC to approximately 100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs, somatic drivers, and support a role of immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of underlying biology, and impact personalized screening strategies and drug development.

Accumulating epidemiologic evidence indicates that high consumption of red meat and of processed meat may increase the risk of colorectal cancer. We quantitatively assessed the association between red meat and processed meat consumption and the risk of colorectal cancer in a meta-analysis of prospective studies published through March 2006. Random-effects models were used to pool study results and to assess dose-response relationships. We identified 15 prospective studies on red meat (involving 7,367 cases) and 14 prospective studies on processed meat consumption (7,903 cases). The summary relative risks (RRs) of colorectal cancer for the highest vs. the lowest intake categories were 1.28 (95% confidence interval (CI) 5 1.15-1.42) for red meat and 1.20 (95% CI 5 1.11-1.31) for processed meat. The estimated summary RRs were 1.28 (95% CI 5 1.18-1.39) for an increase of 120 g/day of red meat and 1.09 (95% CI 5 1.05-1.13) for an increase of 30 g/day of processed meat. Consumption of red meat and processed meat was positively associated with risk of both colon and rectal cancer, although the association with red meat appeared to be stronger for rectal cancer. In 3 studies that reported results for subsites in the colon, high consumption of processed meat was associated with an increased risk of distal colon cancer but not of proximal colon cancer. The results of this meta-analysis of prospective studies support the hypothesis that high consumption of red meat and of processed meat is associated with an increased risk of colorectal cancer. ' 2006 Wiley-Liss, Inc.Key words: cohort studies; meat; meta-analysis; prospective studies; systematic review High consumption of red meat and processed meat has been associated with increased risk of colorectal cancer in many epidemiologic studies, although the associations were usually not statistically significant. A meta-analysis of prospective studies published through June 1999 reported that a daily increase of 100 g of red meat or 25 g of processed meat was associated with a 17% and 49%, respectively, increased risk of colorectal cancer.1 Similar associations between red meat and processed meat consumption with colorectal cancer risk were found in another meta-analysis, 2 which included both case-control and prospective studies published through 1999. These 2 meta-analyses did not report prospective results for colon and rectal cancer separately, and there is evidence that colon and rectal cancers as well as those in the proximal and distal colon may have distinct etiologies. [3][4][5] Ten prospective studies 4-13 have since 1999 been published on red meat and/or processed meat consumption in relation to risk of colorectal cancer. The current meta-analysis updates and expands the previous meta-analyses 1,2 to include all prospective studies on this issue published through March 2006. This meta-analysis includes up to 6 times as many cases of colorectal cancer as the 2 earlier meta-analyses, thus providing more precise risk estimates. Herein, we also report summary results fo...

IMPORTANCE Covert vascular brain injury (VBI) is highly prevalent in community-dwelling older persons, but its clinical and therapeutic implications are debated. OBJECTIVE To better understand the clinical significance of VBI to optimize prevention strategies for the most common age-related neurological diseases, stroke and dementia. DATA SOURCE We searched for articles in PubMed between 1966 and December 22, 2017, studying the association of 4 magnetic resonance imaging (MRI) markers of covert VBI (white matter hyperintensities [WMHs] of presumed vascular origin, MRI-defined covert brain infarcts [BIs], cerebral microbleeds [CMBs], and perivascular spaces [PVSs]) with incident stroke, dementia, or death. STUDY SELECTION Data were taken from prospective, longitudinal cohort studies including 50 or more adults. DATA EXTRACTION AND SYNTHESIS We performed inverse variance-weighted meta-analyses with random effects and z score-based meta-analyses for WMH burden. The significance threshold was P < .003 (17 independent tests). We complied with the Meta-analyses of Observational Studies in Epidemiology guidelines. MAIN OUTCOMES AND MEASURES Stroke (hemorrhagic and ischemic), dementia (all and Alzheimer disease), and death. RESULTS Of 2846 articles identified, 94 studies were eligible, with up to 14 529 participants for WMH, 16 012 participants for BI, 15 693 participants for CMB, and 4587 participants for PVS. Extensive WMH burden was associated with higher risk of incident stroke (hazard ratio [

Cohort studies of excess body weight and risk of liver cancer were identified for a meta-analysis by searching MEDLINE and EMBASE databases from 1966 to June 2007 and the reference lists of retrieved articles. Results from individual studies were combined using a random-effects model. We identified 11 cohort studies, of which seven on overweight (with a total of 5037 cases) and 10 on obesity (with 6042 cases) were suitable for meta-analysis. Compared with persons of normal weight, the summary relative risks of liver cancer were 1.17 (95% confidence interval (CI): 1.02 -1.34) for those who were overweight and 1.89 (95% CI: 1.51 -2.36) for those who were obese. This meta-analysis finds that excess body weight is associated with an increased risk of liver cancer. Although relatively rare in the United States and other developed countries, liver cancer is the third most common cause of death from cancer worldwide (Parkin et al, 2005). It is rarely detected early and is often fatal within a few months of diagnosis. The 5-year survival rate is only about 6 -11% (Coleman et al, 2003;Ries et al, 2006). The age-adjusted incidence and mortality rates of liver cancer have been increasing rapidly in the United States since the mid-1980s (Ries et al, 2006). While approximately half of this increase can be attributable to hepatitis C virus infection, a minimal or no increase has been related to hepatitis B virus and alcoholic liver disease (El-Serag and Mason, 2000;Hassan et al, 2002). Given that about half of the increase in liver cancer incidence is not related to hepatitis, the major risk factor in a significant proportion of the cases has yet to be identified.Coinciding with the rising incidence of liver cancer, the prevalence of obesity has been increasing markedly over the past two decades worldwide (Larsson and Wolk, 2006). Obesity has been recognised as a risk factor for several malignancies, including cancer of the breast (in premenopausal women), endometrium, kidney (renal cell), colon, pancreas, gallbladder, and esophagus (adenocarcinoma) (IARC, 2002;. Accumulating epidemiologic evidence also indicates that excess body weight may be a risk factor for liver cancer, but the evidence has not been quantitatively summarised. We have therefore quantitatively assessed the associations of overweight and obesity with liver cancer risk in a meta-analysis of cohort studies. MATERIALS AND METHODS Study selectionA literature search was conducted in the MEDLINE and EMBASE databases for pertinent studies published in any language from 1966 to June 2007. We used the keywords 'body mass index', 'BMI', or 'obesity' in combination with 'hepatocellular carcinoma', 'liver cancer', or 'liver neoplasm'. Moreover, we manually reviewed the reference lists of retrieved articles to search for more studies.Studies were included in the meta-analysis if they fulfilled the following criteria: (1) cohort study in which liver cancer incidence or mortality was an outcome; (2) the exposure of interest was overweight and/or obesity defined by body ma...