Relative Risk Of Colorectal Cancer Research Articles

Postmenopausal hormone use and risk for colorectal cancer and adenoma.

Accumulating evidence suggests that postmenopausal hormone use may decrease the risk for colorectal cancer. To examine the relation of postmenopausal hormone therapy to colorectal adenoma and cancer. Prospective cohort and nested case-control studies. Nurses' Health Study, a study of registered nurses recruited from 11 U.S. states. 59 002 postmenopausal participants in the Nurses' Health Study. Self-reported data on hormone use and cases of distal colorectal adenoma and colorectal cancer obtained from biennial questionnaires completed from 1980 to 1994. Cases of colorectal adenoma and cancer were confirmed by medical record review. 470 women developed colorectal cancer, and 838 developed distal colorectal adenomas. Current use of postmenopausal hormones was associated with a decreased risk for colorectal cancer (relative risk [RR], 0.65 [95% CI, 0.50 to 0.83]). This association was attenuated in past users (RR, 0.84 [CI, 0.67 to 1.05]) and disappeared 5 years after hormone use was discontinued (RR, 0.92 [CI, 0.70 to 1.21]). Longer duration of current use did not afford greater protection (RR with > or =5 years of use, 0.72 [CI, 0.53 to 0.96]). Even after exclusion of women who reported having screening sigmoidoscopy, the relative risk for colorectal cancer seen with current hormone use was 0.64 (CI, 0.49 to 0.82). This suggests that the apparent protection is unlikely to be due to more intensive screening among hormone users. Current users also had a lower risk for large (> or =1 cm) adenomas than did women who had never used hormones (RR, 0.74 [CI, 0.55 to 0.99]), although no overall material association was seen between colorectal adenoma and current hormone use (RR, 0.91 [CI,0.77 to 1.08]). The risk for colorectal cancer was decreased among women currently receiving postmenopausal hormone therapy, but the apparent reduction substantially diminished upon cessation of therapy. Hormone use was inversely associated with large colorectal adenomas but not small ones.

The nuclear eicosanoid receptor, PPARgamma, is aberrantly expressed in colonic cancers.

Continuous use of nonsteroidal anti-inflammatory drugs (NSAIDs) lowers the relative risk of colorectal cancer in humans and decreases tumor yield in rodents treated with carcinogens. One well documented target for NSAIDs is prostaglandin endoperoxide synthase (cyclooxygenase) and two isoforms of this enzyme have been identified, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX enzymes produce eicosanoid products, some of which have recently been shown to activate transcription mediated by the nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPARgamma), whose expression is largely restricted to adipose tissue. The present study was undertaken to determine if PPARgamma was expressed in colonic tumors. PPARgamma messenger RNA (mRNA) and protein levels were assayed in colonic tumors and normal adjacent mucosa, as well as in a variety of human colon cancer cell lines. There was a marked increase in PPARgamma RNA levels in four out of four of the colonic tumors compared to paired normal mucosa, where little expression of PPARgamma was detected. Western blotting analysis showed that PPARgamma protein was expressed in four out of five colonic tumor samples. PPARgamma was also expressed in a subset of polyps, and in certain human colon cancer cell lines as well. Additionally, we were able to demonstrate that an eicosanoid, 15 deoxy-delta12,14 PGJ2, transactivated transcription of a PPRE-driven promoter in CaCo-2 cells. Thus, we have shown that PPARgamma gene and protein expression is elevated in rodent colon tumors, in selected human colon cancer cell lines and that the PPARgamma receptor is functional in CaCo-2 cells. Since PPARgamma is a ligand-modulated transcription factor, it may provide a novel target for chemopreventive strategies for colorectal cancer.

Cyclooxygenase, NSAIDs, and colorectal cancer.

Prevention of human diseases has become a major focus of biomedical investigators around the world. Our current screening and treatment regimens for colorectal cancer are not effective, as indicated by the fact that this disease is the second leading cause of death from cancer in the United States. Recently published reports indicate that continuous use of aspirin reduces the relative risk of colorectal cancer by about 50%. Other work demonstrates that NSAIDs cause regression of adenomas in patients with familial adenomatous polyposis and prevent the development of colon tumors in carcinogen-treated animals. This review is a summary of the literature and includes an analysis of recent reports indicating the potential molecular basis for the chemoprotective effects of NSAIDs.

Hereditary susceptibility to colorectal cancer

Close relatives of patients with colorectal cancer are at an increased risk of developing a colorectal malignancy themselves. PURPOSE. A study was conducted to compare risks in relatives of patients diagnosed at different ages. METHODS. Family histories were taken from two cohorts of patients with colorectal cancer: Group A, a population group of 65 patients diagnosed at or under 45 (median, 42) years; Group B, 212 patients of all ages (median, 68 years) treated in a single surgeon's practice. RESULTS. Overall relative risk of colorectal cancer in first-degree relatives was 5.2 in Group A and 2.3 in Group B. There was familial clustering of colorectal cancers suggestive of hereditary nonpolyposis colorectal cancer in 13 (20 percent) families in Group A but in only 3 (1.5 percent) families in the second group. Cumulative incidence of colorectal cancer for relatives of the young cohort rose steeply from 40 years, reaching 5 percent at age 50 years and 10 percent at age 70 years. This contrasts with risk for relatives of older patients, in whom the shape of the curve resembles that of the overall population risk, reaching 5 percent at age 70 years and 10 percent at age 80 years. CONCLUSIONS. There appears to be a quantitative and qualitative increase in risk to relatives of patients diagnosed at a young age compared with those diagnosed later in life, at least part of which is likely to be the result of a hereditary susceptibility. Close relatives of early onset cases warrant more intensive endoscopic screening and at an earlier age than relatives of patients diagnosed at older ages.

Risk of colorectal neoplasia in patients with primary sclerosing cholangitis

BACKGROUND & AIMS: Studies implicating primary sclerosing cholangitis as a risk factor for colorectal neoplasia in patients with ulcerative colitis have been limited by small sample size and referral bias. The aim of this study was to determine the relative risk and cumulative incidence of colorectal neoplasia in a large sample of patients with sclerosing cholangitis. METHODS: A sample of patients with primary sclerosing cholangitis (n = 178), stratified by geographic area of residence, was identified and followed up to determine survival and development of colorectal neoplasia. The relative risk of colorectal cancer was determined using age- and sex-specific incidence rates of colorectal cancer in the U.S. general population as well as rates in patients with ulcerative colitis from central Sweden. RESULTS: The relative risk of colorectal cancer was elevated 10-fold (standardized morbidity ratio, 10.3; 95% confidence interval, 2.1-30) compared with the general population for exposure to both sclerosing cholangitis and colitis but not cholangitis alone (standardized morbidity ratio, 4.9; 95% confidence interval, 0.1-27). The observed number of cancers was similar to that expected on the basis of rates in Swedish patients with ulcerative colitis. CONCLUSIONS: If primary sclerosing cholangitis is an additional risk factor for neoplasia in ulcerative colitis, the clinical significance of the risk seems to be low. (Gastroenterology 1996 Feb;110(2):432-40)

Risk of Colorectal Cancer in the Families of Patients with Adenomatous Polyps

The adenoma-adenocarcinoma sequence in colorectal cancer suggests an increased risk of colorectal cancer in the families of patients with adenomatous polyps. A random sample of participants in the National Polyp Study who had newly diagnosed adenomatous polyps were interviewed for information on the history of colorectal cancer in their parents and siblings. The risk of colorectal cancer in family members was analyzed according to the characteristics of the patients with adenomas and in comparison with a sample of patients' spouses, who served as controls. Among the patients with adenomas, 1199 provided information on whether they had a family history of colorectal cancer. After the exclusion of families for which information was incomplete and of 48 patients who had been referred for colonoscopy solely because they had a family history of colorectal cancer, there were 1031 patients with adenomas, 1865 parents, 2381 siblings, and 1411 spouse controls. The relative risk of colorectal cancer, adjusted for the year of birth and sex, was 1.78 for the parents and siblings of the patients with adenomas as compared with the spouse controls (95 percent confidence interval, 1.18 to 2.67). The relative risk for siblings of patients in whom adenomas were diagnosed before 60 years of age was 2.59 (95 percent confidence interval, 1.46 to 4.58) as compared with the siblings of patients who were 60 or older at the time of diagnosis and after adjustment for the sibling's year of birth and sex and a parental history of colorectal cancer. The risk increased with decreasing age at the time of the diagnosis of adenoma (P for trend < 0.001). The relative risk for the siblings of patients who had a parent with colorectal cancer, as compared with those who had no parent with cancer, was 3.25 (95 percent confidence interval, 1.92 to 5.52), after adjustment for the sibling's year of birth and sex and the patient's age at diagnosis. Siblings and parents of patients with adenomatous polyps are at increased risk for colorectal cancer, particularly when the adenoma is diagnosed before the age of 60 or--in the case of siblings--when a parent has had colorectal cancer.

Association of rectal prolapse with colorectal cancer

Although screening for colorectal cancer facilitates earlier detection and improves survival, cost-effective screening requires identification of patients at high risk for colorectal cancer. Rectal prolapse has not been clearly linked to colorectal carcinoma. Whether patients with rectal prolapse should be screened for colorectal cancer is therefore unclear. We retrospectively identified 70 consecutive patients treated for rectal prolapse at a community hospital during a period of 16 years and monitored for an average of 4.4 +/- 2.7 years and 350 patients of similar age treated for chronic unrelated conditions in the same institution during a similar period. We determined their incidence of colorectal cancer and sought demographic correlates. The prevalence of rectosigmoid carcinoma among patients with prolapse was 5.7% during the study. Only 1.4% of the comparative group had colorectal cancer. Thus patients with rectal prolapse exhibited a 4.2-fold (95% confidence interval, 1.1 to 16.0) relative risk for colorectal cancer over the comparative group (p < 0.02). To the extent to which these patients represent the population of patients with rectal prolapse, routine initial screening of patients with symptomatic rectal prolapse by use of flexible sigmoidoscopy may be appropriate.

A Prospective Study of Family History and the Risk of Colorectal Cancer

A family history of colorectal cancer is recognized as a risk factor for the disease. However, as a result of the retrospective design of prior studies, the strength of this association is uncertain, particularly as it is influenced by characteristics of the person at risk and the affected family members. We conducted a prospective study of 32,085 men and 87,031 women who had not previously been examined by colonoscopy or sigmoidoscopy and who provided data on first-degree relatives with colorectal cancer, diet, and other risk factors for the disease. During the follow-up period, colorectal cancer was diagnosed in 148 men and 315 women. The age-adjusted relative risk of colorectal cancer for men and women with affected first-degree relatives, as compared with those without a family history of the disease, was 1.72 (95 percent confidence interval, 1.34 to 2.19). The relative risk among study participants with two or more affected first-degree relatives was 2.75 (95 percent confidence interval, 1.34 to 5.63). For participants under the age of 45 years who had one or more affected first-degree relatives, the relative risk was 5.37 (95 percent confidence interval, 1.98 to 14.6), and the risk decreased with increasing age (P for trend, < 0.001). A family history of colorectal cancer is associated with an increased risk of the disease, especially among younger people.

Clinicopathological significance of the gene expression of matrix metalloproteinase-7, insulin-like growth factor-1, insulin-like growth factor-2 and insulin-like growth factor-1 receptor in patients with colorectal cancer: Insulin-like growth factor-1 receptor gene expression is a useful predictor of liver metastasis from colorectal cancer

Matrix metalloproteinase-7 (MMP-7), secreted by cancer cells, has been implicated classically in the basement membrane destruction associated with tumor cell invasion and metastasis. Epidemiological studies have established a correlation between high levels of circulating insulin-like growth factor-1 (IGF-1) and the relative risk of colorectal cancer, which is known to produce MMP-7. We examined the clinicopathological significance of the relative expression of MMP-7, IGF-1, IGF-2 and IGF-1 receptor genes in patients with colorectal cancer, especially with regard to metastasis. We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 205 patients with untreated colorectal carcinoma. MMP-7, IGF-1, IGF-2, IGF-1R and beta-actin mRNA in cancer tissue and adjacent normal mucosa were measured by quantitative real-time reverse-transcriptase polymerase chain reaction. MMP-7 and IGF-1R gene expression levels were higher in cancer tissue than in adjacent normal mucosa. In contrast, IGF-1 gene expression was lower in cancer tissue than in adjacent normal mucosa. As for the relationship of gene expression to clinicopathological factors, IGF-1R expression correlated with venous invasion and liver metastasis. IGF-1R gene expression is thus considered a useful predictor of liver metastasis from colorectal cancer.

Ulcerative Colitis and Colorectal Cancer

The risk of colorectal cancer is increased among patients with ulcerative colitis. The magnitude of this increase in risk and the effects of the length of follow-up, the extent of disease at diagnosis, and age at diagnosis vary substantially in different studies. To provide accurate estimates of the risk of colorectal cancer among patients with ulcerative colitis, we studied a population-based cohort of 3117 patients given a diagnosis of ulcerative colitis from 1922 through 1983 who were followed up through 1984. Ninety-two cases of colorectal cancer occurred in 91 patients. As compared with the expected incidence, the incidence of colorectal cancer in the cohort was increased (standardized incidence ratio [ratio of observed to expected cases] = 5.7; 95 percent confidence interval, 4.6 to 7.0). Less extensive disease at diagnosis was associated with a lower risk; for patients with ulcerative proctitis, the standardized incidence ratio was 1.7 (95 percent confidence interval, 0.8 to 3.2); for those with left-sided colitis, 2.8 (95 percent confidence interval, 1.6 to 4.4); and for those with pancolitis (extensive colitis, or inflammation of the entire colon), 14.8 (95 percent confidence interval, 11.4 to 18.9). Age at diagnosis and the extent of disease at diagnosis were strong and independent risk factors for colorectal cancer. For each increase in age group at diagnosis (less than 15 years, 15 to 29 years, 30 to 39 years, 40 to 49 years, 50 to 59 years, and greater than or equal to 60 years), the relative risk of colorectal cancer, adjusted for the extent of disease at diagnosis, decreased by about half (adjusted standardized incidence ratio = 0.51; 95 percent confidence interval, 0.46 to 0.56). The absolute risk of colorectal cancer 35 years after diagnosis was 30 percent for patients with pancolitis at diagnosis and 40 percent for those given this diagnosis at less than 15 years of age. Close surveillance and perhaps even prophylactic proctocolectomy should be recommended for patients given a diagnosis of pancolitis, especially those who are less than 15 years of age at diagnosis.

A meta-analysis of alcoholic beverage consumption in relation to risk of colorectal cancer

Quantitative methods were used to review epidemiologic data relating consumption of alcoholic beverages to risk of colorectal cancer. The data (27 studies) supported the presence of a weak association. For consumption of two alcoholic beverages daily, on average the relative risk of colorectal cancer was 1.10 (95% confidence interval 1.05-1.14). Other findings were: (1) the association did not vary according to gender or site within the large bowel; (2) results from follow-up studies (relative risk 1.32, 95% confidence interval 1.16-1.51) suggested a stronger relationship than those from case-control studies (relative risk 1.07, 95% confidence interval 1.02-1.12); and (3) the evidence supporting beverage specificity was not conclusive, although the results were consistent with a stronger association with consumption of beer (relative risk 1.26, 95% confidence interval 1.13-1.41) than with consumption of wine (relative risk 1.11, 95% confidence interval 0.91-1.36) or liquor (relative risk 1.13, 95% confidence interval 0.99-1.29). Because the magnitude of the association between alcohol consumption and risk of colorectal cancer was small, the findings regarding a causal role of alcohol were inconclusive.

Familial colorectal cancer and the screening of family members

A case-control study was undertaken of the family histories of colorectal cancer in 128 patients with colorectal cancers and those of 61 patients with colorectal adenomas and matched surgical control patients who were attending a regional surgical service in Western Australia. One family with multiple polyposis of the colon was excluded from the study. A history of colorectal cancer in one or more first-degree relatives was associated with a relative risk of colorectal cancer of 2.5 (95% confidence interval, 0.8 to 8.0), of adenoma of 2.0 (95% confidence interval, 0.5 to 8.0) and of any colorectal neoplasm of 2.3 (95% confidence interval, 0.9 to 5.6). Four patients with colorectal cancer and one patient with colorectal adenoma had more than one first-degree relative with colorectal cancer, whereas no control subject gave this history. The five families that were represented by these cases each showed some other features of non-polyposis familial colorectal cancer. It was estimated that familial factors could explain 60% of colorectal cancer in persons with a family history of the disease in a first-degree relative and 5% of colorectal cancer in the population as a whole. Haemoccult II tests were posted to 629 living first-degree relatives of the patients with colorectal cancers and adenomas; 44% of these relatives returned the completed tests. Four relatives with positive results of tests both before and after dietary restriction were investigated; all four subjects had colorectal adenomas. In addition, one subject had a short segment of ulcerative colitis. A further mailing of Haemoccult II tests one year later gave a 39% response rate; no further cases of colorectal neoplasia were found. One relative developed carcinoma of the caecum 10 months after a negative result in the first round of Haemoccult screening. Persons with two or more first-degree relatives with colorectal cancer, with or without other features of non-polyposis familial colorectal cancer, are at a high risk of the development of colorectal cancer. The comparatively-poor response to an offer of Haemoccult II testing and its known insensitivity and lack of specificity suggest that it is not a satisfactory method of screening these high-risk subjects.

Relative risk of colorectal cancer after cholecystectomy

The relative risk of developing colorectal cancer after cholecystectomy was assessed retrospectively in 493 patients with colorectal cancer (239 women, 254 men). The results were compared with a control group of patients matched for sex and age. The overall relative risk was 0.7 (90% confidence interval, 0.7-0.8). However, when the data were analysed for site significant differences were seen. In the caecum and ascending colon the relative risk of developing colorectal cancer after cholecystectomy was 2.8 (90% confidence interval, 1.0-9.4). In the rectum the relative risk was only 0.3 (90% confidence interval, 0.2-0.6) in both sexes. The results suggest a relative increased risk of developing right-sided colon cancer after cholecystectomy in women. However, they only partially support the hypothesis that prior cholecystectomy increases the relative risk of developing colorectal cancer in view of the data relating to the rectum.

Cigarette smoking and the risk of colorectal cancer in women.

Colorectal cancer incidence rates for smokers, nonsmokers living with smokers (i.e., passive smokers), and nonsmokers in smoke-free households were compared in a 12-year prospective study of 25,369 women who participated in a private census conducted in Washington County, MD, in 1963. Women who smoked had a decreased relative risk of colorectal cancer compared with the risk for nonsmokers (age-adjusted relative risk, 0.76; 95% confidence interval, 0.52-1.10). The risk for passive smokers was similar to that for smokers. The relative risks were significantly reduced for older women; relative risks were 0.42 for smokers and 0.66 for passive smokers over age 65. The data suggest that older women who smoke have a lower risk of colorectal cancer than nonsmokers. The effect may be mediated by an antiestrogenic effect of smoking.

Family history of colorectal cancer as a risk factor for benign and malignant tumours of the large bowel. A case-control study.

The relationship between first degree family history of colorectal cancer and the risk of benign or malignant tumours of the large bowel was investigated in a case-control study. Two groups of cases (283 patients with adenomatous polyps and 414 patients with adenocarcinoma of the large bowel) and 2 groups of controls (399 polyp-free subjects and 456 hospitalized patients) were interviewed. Since no difference in the frequency of family history between the 2 control groups was detected, these were lumped together. A 3-fold increase in risk of adenomatous polyps in relatives of patients with colon cancer was observed (OR = 3.18, 95% CI 2.06-4.89). The relative risk of colorectal cancer among relatives of patients with adenocarcinoma was 2.36 (95% CI 1.54-3.60). No significant difference in the frequency of first degree relatives with a history of cancer of the large bowel was detected between patients with colorectal cancer and those with adenomatous polyps. When only history of colorectal cancer among parents was considered, the results closely paralleled those of the previous analysis.

Cancers of the large bowel.Associated disorders in individuals

The individual medical histories in the files of the Oxford Record Linkage Study for the years 1963 to 1967 were analyzed to ascertain any previously unsuspected associations between cancers of the large bowel and other diseases in individuals, and to quantify the relative risks of disorders already known to be associated. In males significant associations were shown between cancers of the large bowel and cancer of the prostate. In females, cancer of the colon was associated with breast cancer, and cancer of the rectum with a mixed group of genital cancers. The relative risk of colorectal cancer associated with previous benign neoplasms of the large bowel was 20, and with ulcerative colitis, 25. There was no significant association with appendicitis or long-standing diverticular disease.