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BackgroundPrevious studies have shown that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) lower colorectal cancer (CRC) risk. However, the lowest effective NSAID dose, treatment duration, and effects on survival are not defined. In a large population-based case–control study, we have explored the relationship between NSAID dose and duration, CRC risk and overall CRC-specific survival.MethodsThe relationship between NSAID use and CRC risk was examined in 2279 cases and 2907 controls. Subjects completed food-frequency and lifestyle questionnaires. NSAID categories were low-dose aspirin (75 mg), non-aspirin NSAIDs (NA-NSAIDs) and any NSAID. Users were defined as taking >4 tablets/week for >1 month. ORs were calculated by logistic regression models and adjusted for potential confounding factors. Effect of NSAID use on all-cause and CRC-specific mortality was estimated using Logrank tests and Cox's hazard models.ResultsIn all, 354 cases (15.5%) were taking low-dose aspirin compared to 526 controls (18.1%). Low-dose aspirin use was associated with decreased CRC risk (OR 0.78 95% CI 0.65 to 0.92, p=0.004), evident after 1 year and increasing with duration of use (ptrend=0.004). NA-NSAID and any NSAID use were also inversely associated with CRC. There was no demonstrable effect of NSAIDS on all-cause (HR 1.11, p=0.22, 0.94–1.33) or CRC-specific survival (HR 1.01, p=0.93, 0.83–1.23).ConclusionThis is the first study to demonstrate a protective effect against CRC associated with the lowest dose of aspirin (75 mg per day) after only 5 years use in the general population. NSAID use prior to CRC diagnosis does not influence survival from the disease.

A group of 870 consecutive patients with colorectal cancer were tested for germ-line mutations in DNA repair genes. A two-stage model was devised to predict the presence of mutations in DNA repair genes. A combination of clinical measures and immunohistochemical staining of the tumor for DNA repair proteins gave a positive predictive value of 80 percent and a sensitivity of 62 percent for mutation carriers. A combination of clinical measures and immunohistochemical staining of the tumor for DNA repair proteins gave a positive predictive value of 80 percent and a sensitivity of 62 percent for mutation carriers. Genes responsible for several autosomal dominant and recessive colorectal-cancer–susceptibility syndromes have been mapped and causative mutations characterized. 1 , 2 Most autosomal dominant syndromes are defined empirically on the basis of family history and clinical and pathological criteria, such as the criteria for hereditary nonpolyposis colorectal cancer (also called the Lynch syndrome). 3 , 4 In clinical practice, however, the use of these approaches creates a bias against low-penetrance alleles, small families, nonpaternity or adoption, and newly arisen mutations. The Lynch syndrome is caused by inactivating mutations of DNA mismatch-repair genes (mostly MSH2, MLH1, and MSH6 ), 5 but many patients with colorectal cancer who . . .

Background In Scotland colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer death. Epidemiological studies have reported conflicting associations between statins and CRC risk and there is one published report of the association between statins and CRC survival. Methods Analysis was carried out on 309 cases and 294 controls from the Scottish Study of Colorectal Cancer (SOCCS). Cox’s hazard and logistic regression models were applied to investigate the association between statin use and CRC risk and survival. Results In an adjusted logistic regression model, statins were found to show a statistically significant association for three of the four statin variables and were found to not show a statistically significant association with either all-cause or CRC-specific mortality (OR 0.49; 95%CI 0.49-1.36; p-value = 0.17 and OR 0.33; 95%CI 0.08-1.35; P-value = 0.12, respectively). Conclusion We did find a statistically significant association between statin intake and CRC risk but not statin intake and CRC-specific mortality. However, the study was insufficiently powered and larger scale studies may be advisable.

Richard Houlston and colleagues identify four new susceptibility loci for colorectal cancer through a meta-analysis of genome-wide association data, followed by replication testing in a large collection of independent samples. The study brings to ten the number of confirmed loci harboring low-penetrance risk alleles for this common malignancy. Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly influence the risk of developing colorectal cancer (CRC). To enhance power to identify additional loci with similar effect sizes, we conducted a meta-analysis of two GWA studies, comprising 13,315 individuals genotyped for 38,710 common tagging SNPs. We undertook replication testing in up to eight independent case-control series comprising 27,418 subjects. We identified four previously unreported CRC risk loci at 14q22.2 (rs4444235, BMP4 ; P = 8.1 × 10 −10 ), 16q22.1 (rs9929218, CDH1 ; P = 1.2 × 10 −8 ), 19q13.1 (rs10411210, RHPN2 ; P = 4.6 × 10 −9 ) and 20p12.3 (rs961253; P = 2.0 × 10 −10 ). These findings underscore the value of large sample series for discovery and follow-up of genetic variants contributing to the etiology of CRC.

In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 × 10 −10 ), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 × 10 −26 ) and 18q21 (rs4939827; OR = 1.2; P = 7.8 × 10 −28 ). Risk was greater for rectal than for colon cancer for rs3802842 ( P < 0.008) and rs4939827 ( P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75–3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology.

Colorectal cancer (CRC) accounts for 9.7% of all cancer cases and for 8 % of all cancer-related deaths. Established risk factors include personal or family history of CRC as well as lifestyle and dietary factors. We investigated the relationship between CRC and demographic, lifestyle, food and nutrient risk factors through a case–control study that included 2062 patients and 2776 controls from Scotland. Forward and backward stepwise regression was applied and the stability of the models was assessed in 1000 bootstrap samples. The variables that were automatically selected to be included by the forward or backward stepwise regression and whose selection was verified by bootstrap sampling in the current study were family history, dietary energy, ‘high-energy snack foods’, eggs, juice, sugar-sweetened beverages and white fish (associated with an increased CRC risk) and NSAIDs, coffee and magnesium (associated with a decreased CRC risk). Application of forward and backward stepwise regression in this CRC study identified some already established as well as some novel potential risk factors. Bootstrap findings suggest that examination of the stability of regression models by bootstrap sampling is useful in the interpretation of study findings. ‘High-energy snack foods’ and high-energy drinks (including sugar-sweetened beverages and fruit juices) as risk factors for CRC have not been reported previously and merit further investigation as such snacks and beverages are important contributors in European and North American diets.

A prospective study of 1540 colorectal cancer cases aged 16-79, diagnosed in Scotland between 3rd January 2002 and 31st December 2003, was conducted. The main aims are: report the number and proportion of cases that perceive they have a family history risk of colorectal cancer; compare waiting time with symptoms and behaviour after development of symptoms, between cases that perceive a family history risk and do not perceive a family history risk; report the number and proportion of cases in this cohort with a family history of colorectal cancer that meet Scottish clinical criteria for high or moderate family history risk. A secondary aim is: describe the average delay time in symptom presentation and the factors contributing to delay in presentation of lower gastrointestinal symptoms among cases with colorectal cancer and in particular assess the importance of deprivation and comorbidity. Results: The distribution of sex and age at diagnosis were similar to other published population-based colorectal cancer studies. Of the 1540 cases, 222 (14.9%) cases perceived they had a family history of colorectal cancer. 280 (18.2%) cases out of 1540 were at a high or moderate family history risk according to Scottish Executive Guidelines. Of these 280 cases, 133 (47.5%) perceived they had a family history of colorectal cancer. Of these 133 cases, only 51 (18.2%) discussed this concern with their GP and, only 12 (4.3%) were referred to cancer genetic services. Cases that perceived a family history risk of colorectal cancer were more likely to state they have knowledge of colorectal cancer symptoms and more likely to think that the lower gastrointestinal symptoms they develop are symptoms of colorectal cancer. However, this knowledge does not prompt them to visit the GP with less delay after symptoms onset than those cases with no perception of a family history risk of colorectal cancer. There was no association found between deprivation, comorbidity and timing of presentation following development of symptoms. The more deprived group of patients were significantly more likely to report no knowledge of colorectal cancer symptoms. They were also less likely not to inspect the toilet or the toilet paper before flushing. Implications for Health service: Providing all health professionals with the knowledge and skills to take a family history and to follow published guidelines when assessing family history risk would share the responsibility for identification of individuals with a high or moderate family, improve the appropriateness of referrals and reduce the inequality in access to cancer genetic services. The most deprived group of patients have the least knowledge of colorectal cancer symptoms and the design of educational material should acknowledge this fact and ensure that it is appropriate for this audience.

Some studies have found a deficiency of male, younger and more socially deprived individuals amongst referrals to and/or attendees at cancer genetics clinics. We investigated this inequality of use of genetics services from data on 4,178 Scottish patients with a family history of breast and/or ovarian cancer (BOC) or colorectal cancer (CRC) referred from 2000–2006. Some 98% BOC and 60% CRC referrals were female. Median age of female referrals was greater in the CRC than the BOC group (45.3 vs. 38.7 years, P  < 0.001). Both groups of referrals were less socially deprived than the general population ( P  < 0.001) and the CRC less deprived than the BOC group ( P  < 0.001). Some 88% patients attended the first appointment offered. Attendance was greater in the CRC group ( P  < 0.001) and in older patients ( P  < 0.001) and in the BOC group was highly significantly lower in more socially deprived patients ( P  < 0.001). Male relatives may feel counselling is less relevant and relatives of both sexes may delay counselling until approaching the age of onset of cancer in a relative. We suggest that medical professionals and the general public may have more knowledge about the genetics of BOC than of CRC. Thus relatives in CRC families seeking counselling are likely to be those with access to more information. The lower attendance amongst more deprived relatives in BOC families may result from poor understanding of the reason for referral. These findings confirm the need to provide male, younger and more socially deprived relatives with more helpful information on cancer genetics.

The discovery that genetic factors are involved in the aetiology of colorectal cancer, has prompted many relatives of affected individuals to seek genetic counselling and screening. This paper describes the demand for genetic services by families with colorectal cancer in south-east Scotland, their expectations and views of the service offered. The annual referral rate over the 21-month study period, for patients with a family history of colorectal cancer, was 0.11 per 1000 patients on general practitioner lists. This is one third of the rate for patients with a family history of breast cancer and in comparison with the breast cancer group, relatives of colorectal cancer patients were significantly older and less socially deprived. Approximately one third were referred via a hospital specialist unit. One hundred patients were included in the study. Mean (+/- standard deviation) age was 43 (+/- 10.7 years), 75 were female and 31 were self referrals. Before the consultation, almost half the patients had an inflated perception of their risk and there was little change at follow-up. There was an improvement in objective understanding after counselling which was sustained up to 6 months but only two thirds remembered their objective risk accurately. Most patients were satisfied with the consultation. Our findings suggest the need to educate individuals, in particular men, younger people and the more socially deprived, about the relevance of a family history of colorectal cancer and to facilitate patients' comprehension of their risk status.