Incidence Of Colorectal Carcinoma Research Articles

Environmental and other risk factors for colorectal carcinogenesis

Diet plays a role in the risk of colon cancer, but exactly how it affects risk is unknown. In western countries diet is low in fibre and high in animal protein, fats and refined carbohydrates such as sugar. Risk seems to be reduced by a diet high in calcium, vitamin D and vegetables such as Brussels sprouts, cabbage and broccoli. Familial polyposis has been studied sufficiently and increases the risk of colon cancer. Moreover, in relatives there is frequently a familial history of an increased incidence of colorectal cancer. There is no conclusive evidence to support any of the hypotheses proposed to explain the role of dietary factors in colorectal carcinogenesis. Prospective trials should generate the information required to develop strategies for diet modification to reduce the incidence of colorectal carcinoma. There is hope that this understanding will lead to a variety of dietary, medical, hormonal and molecular interventions to reduce disease incidence and improve the prognosis of patients with cancers of the colon and rectum.

Postsurgical disparity in survival between African Americans and Caucasians with colonic adenocarcinoma

Colorectal carcinoma (CRC) is the third most common malignancy and the second most common cause of cancer mortality among men and women in the United States. In 2003, there were an estimated 147,500 new cases of CRC and 57,100 deaths due to this malignancy.1 In the United States, there are racial differences in CRC incidence, mortality, and survival. Compared with Caucasians, African Americans have higher incidence and mortality rates and lower survival rates.2 Recent trends indicate that the incidence of CRC among Caucasians has declined slightly and recently stabilized, whereas CRC incidence among African Americans has increased. The racial discrepancy is even more prominent with respect to mortality: Mortality rates have declined steadily for Caucasians, whereas they have increased for African Americans, and particularly African-American men. For each disease stage at diagnosis, 5-year relative survival rates are lower for African Americans with CRC than for Caucasians.2 Several studies of survival differences between African-American and Caucasian patients with CRC have reported poorer prognosis and shorter survival among the former group3–15 (Table 1). These studies analyzed survival and/or mortality among patients with colonic, rectal, or colorectal carcinoma (patients with colonic and rectal tumors were analyzed as a single group). A variety of explanations for the racial disparity in survival have been proposed, including differences in age, advanced disease stage at the time of diagnosis, treatment options, socioeconomic factors, and biologic characteristics (Table 1). TABLE 1 Review of Studies Evaluating Differences in Survival between African Americans and Caucasians with Colorectal Adenocarcinoma We conducted survival analyses to elucidate the differences in survival between African-American patients and Caucasian patients with CRC based on tumor site and tumor stage, because neoplasia of the colon and the rectum should be viewed as distinct disease entities, each with their own prognostic factors. All patients underwent surgery (alone) with curative or palliative intent at the University of Alabama–Birmingham (UAB; Birmingham, AL) or at an affiliated Birmingham Veterans Affairs (VA) hospital. The current clinical cohort of patients may represent the population dynamics of the southeastern United States.

Effect of retinoic acid on cell proliferation kinetics and retinoic acid receptor expression of colorectal mucosa.

To investigate the effect of retinoic acid (RA) on cell proliferation kinetics and retinoic acid receptor (RAR) expression of colorectal mucosa. One hundred sixty healthy male Wistar rats were randomly divided into 4 groups. Rats in groups I and II were subcutaneously injected with dimethylhydrazine (DMH) (20 mg/kg, once a week,) for 7 to 13 weeks, while groups III and IV were injected with normal saline. Rats in groups II and III were also treated with RA (50 mg/kg, every day, orally) from 7th to 15th week, thus group IV was used as a control. The rats were killed in different batches. The expressions of proliferating cell nuclear antigen (PCNA), nucleolar organizer region-associated protein (AgNOR) and RAR were detected. The incidence of colorectal carcinoma was different between groups I (100 %) and II (15 %) (P<0.01). The PCNA indices and mean AgNOR count in group II were significantly lower than those in group I (F=5.418 and 4.243, P<0.01). The PCNA indices and mean AgNOR count in groups I and II were significantly higher than those in the groups III and IV (in which carcinogen was not used) (F=5.927 and 4.348, P<0.01). There was a tendency in group I that the longer the induction with DMH the higher PCNA index and AgNOR count expressed (F=7.634 and 6.826, P<0.05). However, there was no such tendency in groups II, III and IV (F=1.662 and 1.984, P>0.05). The levels of RAR in normal and cancerous tissues in groups treated with RA were significantly higher than those in groups not treated with RA (F=6.343 and 6.024, P<0.05). RA decreases the incidence of colorectal carcinoma induced by DMH. Colorectal cancer tissue is associated with abnormal expression of PCNA, AgNOR and RAR. RA inhibits the expression of PCNA and AgNOR, and increases RAR concentration in colorectal tissues.

Colorectal cancer screening: a challenge for magnetic resonance colonography.

The high incidence of colorectal carcinoma and the fact that colorectal cancer mostly arises from benign adenomas have led to recommendations for screening programs. The introduction of ultrafast three-dimensional datasets acquired by cross-sectional imaging modalities (computed tomography or magnetic resonance imaging) in combination with new postprocessing modes, known as virtual endoscopy, has led to new discussion on the recommendation of screening tests for colorectal cancer. Published results have indicated a high sensitivity for computed tomographic colonography and magnetic resonance-based colonography. Both techniques currently must be combined with colon cleansing. Three-dimensional data acquisition for magnetic resonance-based colonography is less than 1 minute using three-dimensional gradient-echo sequences. The lack of ionizing radiation, the low risk and discomfort to patients, and new techniques of minimized patient preparation make this magnetic resonance technique an attractive diagnostic procedure for colorectal lesions, with many aspects for use as a screening method.

Change in anatomic distribution and incidence of colorectal carcinoma over a period of 15 years: clinical considerations.

Colorectal cancer is the second most common cancer in the Netherlands. Its incidence rates are among the highest in Europe. In the past decades, a right-sided shift of the subsite location of colorectal cancer has been reported. These changes in anatomic distribution might have clinical implications for the use of diagnostic or screening tools for colorectal cancer. This study was designed to investigate the change in incidence and anatomic distribution of colorectal cancer in a population over a period of 15 years. The incidence of colorectal cancer in an eastern part of the Netherlands (700,000 inhabitants) was determined for two years, 1981 and 1996. From the regional laboratory of pathology, data including age, gender, subsite location, and Dukes classification were collected. The subsite location of colorectal cancer was divided into two groups: proximal and distal (the latter being within sigmoidoscopy reach). No differences in age and gender distribution were found. In 1981, the diagnosis of colorectal cancer was made in 232 patients in this region, and in 1996, it was made in 410 patients. The population remained almost stable during this time. Therefore, the incidence rose from 33 to 55 per 100,000 inhabitants from 1981 to 1996, respectively. In 1981, 25 percent of the carcinomas were proximal (to the sigmoid colon); this increased to 37 percent in 1996 ( P< 0.05). The incidence of colorectal cancer has almost doubled from 1981 to 1996 in this Dutch region. The proportion of proximal colorectal cancer has increased from 25 to 37 percent. These findings add to the notion that sigmoidoscopy is not the optimal diagnostic or screening tool for colorectal cancer.

Clinical and screening implications of the I1307K adenomatous polyposis coli gene variant in Israeli Ashkenazi Jews with familial colorectal neoplasia. Evidence for a founder effect.

The authors previously found the I1307K adenomatous polyposis coli (APC) gene variant in 5% of Ashkenazi control participants, in 15.4% of those who had familial colorectal neoplasia, but also in 1.6% of non-Ashkenazi control participants. In this study, they evaluated its use in a screening program for familial colorectal neoplasia and examined for a founder effect. Consecutive Ashkenazim with a personal and/or family history of colorectal neoplasia had the DNA test. Markers flanking the APC gene were examined in Ashkenazi and non-Ashkenazi I1307K carriers and noncarriers. Among 718 persons, I1307K occurred in 6.2% of Ashkenazi participants, in 1.5% of non-Ashkenazi control participants (P = 0.02), and in 10.7% of Ashkenazim with familial neoplasia (relative risk, 1.73 [not significant compared with controls]; 95% confidence interval, 0.7-3.2). Colorectal neoplasia was detected in carriers at a younger age (P < 0.05) without excess risk for multiple colorectal neoplasia or noncolorectal neoplasia. I1307K attributable risk for colorectal neoplasia was 0.5-0.6%. Compared with noncarriers, both Ashkenazi and non-Ashkenazi I1307K carriers had similar flanking polymorphic alleles (P < 0.01). I1307K is a low-penetrance genetic variant that indicates a 1.7 relative risk for neoplasia in carriers who have familial carcinoma, clinically equivalent to obtaining a family history of sporadic colorectal neoplasia and promoting early screening. I1307K is a founder genetic variant in Jews of different ethnic origin, mainly Ashkenazim, but it explains only partially their higher incidence of colorectal carcinoma.

Comparative study for histology, proliferative activity, glycoproteins, and p53 protein between old and recent colorectal adenomas in Japan

The incidence of colorectal carcinoma is increasing in Japan. Malignant transformation in colorectal neoplasia is usually considered to be owing to adenoma-carcinoma sequence. Elucidation of the recent alteration in the biological properties of colorectal adenoma is sure to be useful to understand the recent increase of the colorectal carcinoma in Japan. We compared the histopathological feature, mitotic index, proliferative activity (Ki-67 labeling index), expression of glycoproteins such as MUC2 mucin, sialyl Lewis A (SLe a) and sialyl dimeric Lewis X (SLe x), and p53 protein overexpression, between 108 adenomas in the old period (Group A, from 1969 to 1985) and 140 adenomas in the recent period (Group B, from 1995 to 1998). The histological dysplasia, mitotic index and Ki-67 labeling index of the adenomas were significantly higher in Group B than in Group A. In contrast, the expression of MUC2 mucin, which is considered to be a differentiation factor of intestinal mucosal epthelium, was significantly reduced in Group B than in Group A. The SLe a and SLe x expressions showed no significant difference between them. The p53 expression showed no significant difference between them, except for the moderate dysplasia. These findings indicate that recent colorectal adenomas show more advanced degrees of histological dysplasia, more rapid growth, and reduced differentiation than colorectal adenomas, which developed at earlier times, and may be related with the recent high incidence of colorectal carcinoma in Japan.

Molecular Evidence for Multicentric Development of Thyroid Carcinomas in Patients with Familial Adenomatous Polyposis

Familial adenomatous polyposis is characterized by multiple colorectal adenomas and an increased incidence of colorectal carcinomas. Patients also develop various extracolonic tumors, of which, thyroid carcinoma is common in young females. The occurrence of multiple carcinomas in one thyroid is frequently observed, although some carcinomas are solitary. To clarify whether each carcinoma develops independently or metastatically spreads from the first one formed, we analyzed the adenomatous polyposis coli (APC) gene mutation in each carcinoma. We found that each carcinoma had a different somatic mutation of the APC gene. This is molecular confirmation for the multicentric development of thyroid carcinomas in familial adenomatous polyposis through biallelic inactivation of the APC gene.

Clinical management and genetics of gastrointestinal polyps in children.

Clinical management and genetics of gastrointestinal polyps in children.

Microsatellite instability and K- ras mutations in patients with ulcerative colitis

Patients with inflammatory bowel disease (BD), particularly ulcerative colitis (UC), have an increased incidence of colorectal carcinoma. The underlying mechanism is unknown, but we postulated that microsatellite instability (MSI) might predispose the colonic mucosa of UC patients to mutations, thereby increasing their cancer risk. We also sought to determine the frequency of K- ras mutations, to determine whether MSI predisposed to Kras mutations and to compare the molecular phenotype of biopsy and resection specimens in the same patient. We also sought to determine whether molecular alterations found in biopsy specimens presaged their presence in subsequent resection specimens. Two hundred fifty-eight specimens from 52 patients were examined for K- ras mutations by direct sequencing. Seventy-one of the specimens were neoplastic. MSI was evaluated after polymerase chain reaction (PCR) amplification using primers directed at 8 microsatellite loci. Of the patients, 18.2% had K- ras mutations, and 30.8% had MSI in at least 1 locus. Of K- ras mutations, 81.8% were G to A substitutions involving the second nucleotide of codons 12 or 13. Only 0.7% of the samples showed a high level of MSI. No relationship existed between MSI and K- ras mutations, even in the 2 samples with high-level MSI. The numbers are small, but it appeared that MSI in biopsies failed to predict its presence in resection specimens. In contrast, K- ras mutations present in biopsy specimens tended to predict their presence in resections. K- ras mutations were found predominantly in neoplastic mucosae, whereas MSI was found predominantly in regenerative mucosae. The lack of any relationship between MSI and K- ras mutations suggests that MSI in the UC replicative mucosa does not predispose to colonic neoplasia via a K- ras-mediated pathway. This is probably related to the fact that the MSI is generally low-level MSI.

A study of colo-rectal carcinoma in the Asian and European populations in the city of Leicester from 1981 to 1991

For many years clinical reports have suggested that colo-rectal cancer is uncommon in the Asian population resident in England and a report in 1990 confirmed this in Asians living in Bradford. This study aims to establish the incidence of colo-rectal cancer in the Asian population resident in the city of Leicester during the 11 y period 1 January 1981–31 December 1991. The relative frequency of colo-rectal carcinoma in Asians compared to Europeans over the period studied was 0.16 (Asian/European, 95% confidence interval (CI) 0.04–0.75). This difference was statistically significant and further analysis showed that there was a real trend with an increased relative frequency amongst the younger age groups. Although there was a significantly lower incidence of colo-rectal carcinoma in the Asian population in Leicester city over the period studied it is unknown whether this is due to environmental or genetic factors. During the next decade it is likely to become clearer as to whether this difference will persist or whether there will be an increase in the incidence of colo-rectal carcinoma in Asians in Leicestershire. Public Health (2000) 114, 53–55.

Clinical evidence for the adenoma—carcinoma sequence

A review is given on evidence supporting or rejecting the hypothesis of a colorectal adenoma-carcinoma sequence. The majority of studies discuss adenomas from a clinical point of view, but pathology has also been considered in detail, and molecular biology has been touched on. It is concluded the adenoma stage is, most probably, a phase on the way to carcinoma. But it remains to be shown what effect the removal of adenomas will have in the long run on the incidence of colorectal carcinoma.

Evaluation of a selective screening for colorectal carcinoma

Although the efficacy of mass screening for colorectal carcinoma (CRC) with a fecal occult blood test has been demonstrated in several randomized trials, a mass screening approach used in countries with intermediate or low incidence of CRC might be costly. Screening high risk people may be an alternative approach, to aid in the prevention of death from CRC. However, the efficacy of CRC screening for high risk people in such countries is uncertain. For this study, a multicenter design was devised to identify high risk groups without clinical symptoms related to CRC; these subjects were identified through the study of index cases of CRC in Taiwan. Colonoscopy, in combination with a fecal occult blood test or double-contrast barium enema, was used to screen high risk groups. A total of 8909 subjects were invited to attend screening. Of 8909, 81 with asymptomatic CRC were detected in one-shot screening. Markov models, in conjunction with a simulated approach, were proposed to estimate relevant parameters in relation to disease progression and to assess the effect of the interval between screenings on the efficacy of CRC screening for these high risk groups. The estimated preclinical incidence rate was 0. 00396 (95% confidence interval [CI], 0.002944-0.004985), which was 21 times that reported from a cancer registry in 1994. The simultaneous estimations of mean sojourn time (the average duration between the preclinical screen-detectable phase and the clinical phase) and sensitivity were 2.8 years (95% CI, 2.15-4.30) and 95.0% (95% CI, 24.4-99.9%), respectively. Predictions of mortality reduction for people who received annual, biennial, and triennial screening regimes compared with controls were 26% (95% CI, 0-50%), 23% (95% CI, 0-48%), and 21% (95% CI, 0-47%), respectively. The efficacy of selective colorectal carcinoma screening has been demonstrated in this study. A high preclinical CRC incidence rate also suggests that such a screening strategy might be cost-effective for countries with intermediate or low incidence of CRC. Methods proposed in this study can be used to evaluate the efficacy of CRC screening in similar screening trials.

Primär sklerosierende Cholangitis – Therapieoptionen

The natural course of primary sclerosing cholangitis (PSC) is highly variable. There is no correlation between the PSC activity and the severity of the bowel disease which occurs simultaneously in more than half of the patients. With this variability in the natural history of the disease, the clinician is faced with difficult decisions regarding the timing of medical and interventional therapy as well as of orthotopic liver transplantation. Immunosuppression is unlikely to be effective in patients with advanced liver disease with an irreversible bile duct Ioss. Ursodeoxycholic acid (UDCA) is now commonly prescribed in PSC since the drug is safe in most patients. High-dose UDCA treatment looked promising in a small pilot study. Therefore this approach probably in combination with immunosuppressive treatment should be investigated in prospective long term controlled trials in patients in the prefibrotic stage. Treatment of the PSC symptoms (itching, steatorrhoea, osteoporosis, bacterial cholangitis) is of paramount importance for the quality of life of the patients. Relapsing cholangitis must be treated aggressively with appropriate antibiotics e. g. ciprofloxacine or mezlocillin plus metronidazole. Balloon dilation and short term stenting will help patients with dominant stenoses of the extrahepatic bile ducts. In late-stage PSC liver transplantation is the only therapeutic option. The 5-year survival rate is good (about 80%). Orthotopic liver transplantation should be performed early in the course of the disease when the operative risk is less. At this stage patients are also less likely to have developed hepatobiliary malignancy. The incidence of colorectal carcinoma in PSC patients with ulcerative colitis is high. Therefore, annual surveillance colonoscopy is recommended in this group of patients.

In colorectal carcinoma patients, serum vitamin D levels vary according to stage of the carcinoma.

Epidemiologic studies have demonstrated an inverse correlation between dietary calcium and vitamin D intake and the incidence of colorectal carcinoma. Elevated serum levels of 25-hydroxyvitamin D3 (25-OH-D3) are associated with a major reduction in the incidence of this neoplasm. The reduction in tumor size and number induced by calcium supplements in an experimental carcinogenesis model was neutralized by vitamin D3 deficiency. To the authors' knowledge, vitamin D serum levels have never been determined previously in colorectal carcinoma patients. They compared serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 25-OH-D3, and parathyroid hormone (PTH) levels of colorectal carcinoma patients with those of healthy controls. Serum 1,25(OH)2D3, 25-OH-D3, and PTH levels were determined in 84 colorectal carcinoma patients (10 with Stage I, 29 with Stage II, 25 with Stage III, and 20 with Stage IV) and 30 healthy controls, all of whom were normocalcemic and not taking calcium or vitamin D supplements. 25-OH-D3 serum levels were higher in cancer patients than controls, irrespective of stage. Serum 1,25(OH)2D3 decreased with advancing stage: 73 +/- 18, 48 +/- 16, 39 +/- 12, 34 +/- 13, and 75 +/- 20 pg/mL in Stages I, II, III, IV, and controls, respectively. There was a corresponding increase in serum PTH levels: 58.0 +/- 9.4, 73.7 +/- 14.4, 79.0 +/- 21.3, 100.4 +/- 30.9, and 51.2 +/- 3.9 pg/mL in Stages I, II, III, IV, and controls, respectively. Serum vitamin D metabolite levels did not correlate with gender, age, tumor localization, or histologic grade. An inverse correlation between serum levels of the active metabolite of vitamin D and colorectal carcinoma stage has been demonstrated for the first time, to the authors' knowledge, in colorectal carcinoma patients. Because 1,25(OH)2D3 has been shown to inhibit proliferation of colonic epithelial cells, decreased serum levels may facilitate the growth of colorectal carcinoma and influence its biologic behavior.

Incidence of colorectal carcinoma in the U.S.

Colon carcinoma incidence rates have risen sharply over the second half of this century, particularly among males and blacks. In the late 1970s, incidence rates among whites began to decline for distant disease. Approximately 10 years later regional disease rates began to fall. The decline in incidence rates among whites largely has been attributed to more widespread colorectal carcinoma screening. However, similar trends by stage in blacks have not been observed. The incidence of colorectal carcinoma was evaluated by race, gender, age, and stage of disease for each subsite using data from > 220,000 cases diagnosed between 1975 and 1994 in the U. S. Surveillance, Epidemiology, and End Results program. Recent data have continued to show a decrease in incidence rates of total colorectal carcinoma in whites since the mid-1980s, particularly for the distal colon and rectum. Overall, proximal colon carcinoma rates were higher than distal colon or rectal carcinoma rates throughout the study period. Proximal colon carcinoma rates in blacks were considerably higher than in whites and continued to increase, whereas rates in whites showed signs of declining. The age-specific and stage-specific trends for proximal colon carcinoma in blacks were not consistent with the possibility of earlier disease detection through screening. Etiologic studies are necessary to understand the large increases in the incidence of proximal colon carcinoma among blacks.

Incidence of colorectal carcinoma in the U.S.

BACKGROUND Colon carcinoma incidence rates have risen sharply over the second half of this century, particularly among males and blacks. In the late 1970s, incidence rates among whites began to decline for distant disease. Approximately 10 years later regional disease rates began to fall. The decline in incidence rates among whites largely has been attributed to more widespread colorectal carcinoma screening. However, similar trends by stage in blacks have not been observed. METHODS The incidence of colorectal carcinoma was evaluated by race, gender, age, and stage of disease for each subsite using data from > 220,000 cases diagnosed between 1975 and 1994 in the U. S. Surveillance, Epidemiology, and End Results program. RESULTS Recent data have continued to show a decrease in incidence rates of total colorectal carcinoma in whites since the mid-1980s, particularly for the distal colon and rectum. Overall, proximal colon carcinoma rates were higher than distal colon or rectal carcinoma rates throughout the study period. Proximal colon carcinoma rates in blacks were considerably higher than in whites and continued to increase, whereas rates in whites showed signs of declining. The age-specific and stage-specific trends for proximal colon carcinoma in blacks were not consistent with the possibility of earlier disease detection through screening. CONCLUSIONS Etiologic studies are necessary to understand the large increases in the incidence of proximal colon carcinoma among blacks. Cancer 1999;85:1670–6. © 1999 American Cancer Society.

Expression of cripto and amphiregulin in colon mucosa from high risk colon cancer families.

We assessed the expression of the epidermal growth factor (EGF)-related peptides, cripto-I (CR-I) and amphiregulin (AR), in a small panel of human colon adenomas and carcinomas. CR-I immunoreactivity was found in 17/31 (55%) of colon adenomas, and in 33/39 (84%) colon carcinomas. AR immunostaining was observed in 16/26 adenomas (61%) and in 20/26 carcinomas (77%). CR-I and AR staining were also assessed in 29 specimens from 24 individuals that belong to families with high incidence of colorectal carcinoma, and in 5 non-high risk individuals. Expression of CR-I was detected in 18/29 (62%) of high risk colon mucosa specimens, but only in 1/5 (20%) specimens from non-high risk individuals, while AR staining was found in 20/29 (69%) and in 4/5 (80%) of colon mucosa samples from high and low risk individuals, respectively. A majority (21/29; 72%) of the specimens from the high risk individuals had a high proliferative rate, as measured by Ki-67 staining. A statistically significant correlation was found between high proliferative rate, increased expression of CR-I and reduced expression of AR in the mucosa specimens from high risk individuals, suggesting that these might represent early events in colon tumorigenesis.

Use of Medicare claims data to measure county-level variations in the incidence of colorectal carcinoma.

Population-based cancer registries that can be used to compare cancer incidence and mortality across regions of the U.S. are currently lacking. The authors conducted this study to validate Medicare claims as a measure of county-level colorectal carcinoma incidence among older Americans. Variations found among counties are described in this article. A total of 183,174 hospitalized patients age 65 years in 1991-1993 with newly diagnosed colorectal carcinoma who resided in one of 480 large counties were identified in Medicare files. The county-level truncated age, race, and gender adjusted incidence rates for the population age 65 years, the proportion of patients with a code indicating distant metastases, and the 2-year case-fatality rates were determined. Corresponding rates from the SEER database were compared. The median truncated adjusted 3-year incidence rate was 870 per 100,000 (Quartile 1-Quartile 3, 779-955), with almost twofold differences among counties even after the exclusion of outliers. The median proportion of patients with codes indicating distant metastases was 23.4% (range, 10.2-46.9%; Quartile 1-Quartile 3, 20.8-25.8), and the average 2-year case-fatality rate was 39.2% (range, 26.5-51.4%; Quartile 1-Quartile 3, 37.0-41.6). Medicare files tended to underestimate the truncated incidence rate according to SEER, but among counties the two sets of rates were closely correlated (r = 0.94, P < 0.0001). Medicare files are a potential alternative source of national data for the study of colorectal carcinoma incidence among the elderly at the county level. The data also suggest significant variations among counties in colorectal carcinoma incidence, stage, and mortality that could be used in public health initiatives.

Author reply

Regarding cimetidine, the lack of effect reflected in the 10-year postmarketing survey, other than an excess of colorectal carcinoma in the first year of treatment (which we would attribute to diagnostic difficulty), certainly does not affect our observations. The effect we have described might well be expected to improve the prognoses of patients with established colorectal carcinoma, but this is an entirely different issue from whether cimetidine would affect the incidence of colorectal carcinoma. Similarly, the case-control study cited by Tavani et al. did not describe any effect of cimetidine on the outcome of colon carcinoma. If cimetidine does produce increased tumor-infiltrating lymphocytes in colorectal carcinoma, we believe this would be very likely to improve prognosis, but we cannot see that it would be likely to affect the incidence of this disease. What is really needed is a study of a large number of patients with colorectal carcinoma who did receive cimetidine and a large number who did not. The case-control study simply does not address this issue. David L. Morris*, Warwick J. Adams