Colorectal Cancer In Subjects Research Articles

Colorectal cancer occurs earlier in those exposed to tobacco smoke: implications for screening

Colorectal cancer (CRC) is the third most common cancer in the USA. While various lifestyle factors have been shown to alter the risk for colorectal cancer, recommendations for the early detection of CRC are based only on age and family history. This case-only study examined the age at diagnosis of colorectal cancer in subjects exposed to tobacco smoke. Subjects included all patients who attended RPCI between 1957 and 1997, diagnosed with colorectal cancer, and completed an epidemiologic questionnaire. Adjusted linear regression models were calculated for the various smoking exposures. Of the 3,540 cases of colorectal cancer, current smokers demonstrated the youngest age of CRC onset (never: 64.2 vs. current: 57.4, P < 0.001) compared to never smokers, followed by recent former smokers. Among never smokers, individuals with past second-hand smoke exposure were diagnosed at a significantly younger age compared to the unexposed. This study found that individuals with heavy, long-term tobacco smoke exposure were significantly younger at the time of CRC diagnosis compared to lifelong never smokers. The implication of this finding is that screening for colorectal cancer, which is recommended to begin at age 50 years for persons at average risk should be initiated 5-10 years earlier for persons with a significant lifetime history of exposure to tobacco smoke.

Colorectal Cancer and the Methylenetetrahydrofolate Reductase 677C → T and Methionine Synthase 2756A → G Polymorphisms: A Study of 2,168 Case-Control Pairs from the JANUS Cohort

Abstract Polymorphisms in genes involved in the metabolism of folate and methyl groups have been implicated with risk of colorectal cancer. We evaluated the relation between the polymorphisms 677C → T of the methylenetetrahydrofolate reductase (MTHFR) and 2756A → G of the methionine synthase (MTR) genes and risk of colorectal cancer. From the Norwegian JANUS cohort of 309,000 subjects, 2,179 cases were identified and a similar number of controls were selected. The controls were matched for age, gender, time, and place of serum donation. Genotypes were obtained from 2,168 case-control pairs by real-time PCR of serum samples. Risk of colorectal cancer was estimated with conditional and unconditional logistic regression. Median age at diagnosis was 60 years and mean follow-up 13 years. The odds ratio for MTHFR TT versus CC was 0.73 [95% confidence interval (95% CI), 0.58-0.92] and for MTR GG versus AA was 0.65 (95% CI, 0.47-0.90). No interaction between the polymorphisms was found. Relative risk estimates were similar for men and women, and for young and old age at diagnosis. For the MTR GG genotype, risk reduction was observed at the two most distal sites (sigmoideum and rectum) only (P = 0.003). The folate marker, serum total homocysteine (tHcy), was measured in 1,837 subjects. Odds ratio for the upper versus the lower tertile of tHcy was 1.32 (95% CI, 1.04-1.68). No significant effect modification by tHcy levels was detected for either polymorphism. In summary, we found significantly reduced risk of colorectal cancer in subjects with the MTHFR 677 TT and MTR 2756 GG genotypes. No interaction between the polymorphisms, or of either polymorphism with tHcy, was detected.

GSTM1 Polymorphism Does Not Affect Hereditary Nonpolyposis Colorectal Cancer Age of Onset

<i>GSTM1</i> Polymorphism Does Not Affect Hereditary Nonpolyposis Colorectal Cancer Age of Onset

Recurrence and malignancy rates in a benign colorectal neoplasm patient cohort: results of a 5-year analysis in a managed care environment

OBJECTIVE: To estimate the apparent recurrence rates of benign neoplasms and the development of malignant colorectal neoplasms over a 5-yr period in a high risk managed care population. METHODS: Using the CPT and ICD-9 CM codes, a cohort of subjects with benign neoplasms were identified with a colonoscopy in 1992 from a longitudinal claims database (MarketScan). Three groups of subjects (benign neoplasms with polypectomy, benign neoplasms without polypectomy, and no neoplasms) were evaluated. Five-year recurrence rates of benign or new malignant colorectal neoplasms were determined for the baseline benign neoplasms with polypectomy and no neoplasm groups. For the benign neoplasm without polypectomy, only rates for malignancy were evaluated. RESULTS: Of 16,293 subjects at baseline, 39.50% were diagnosed with benign and 5.50% with malignant neoplasms. The 5-yr cumulative incidence of benign neoplasms in subjects without an index neoplasm (n = 8,967) was 7.92% compared to the recurrence of 40.93% in subjects with a benign neoplasm and polypectomy (n = 4,046) at baseline ( p < 0.001). The 5-yr cumulative incidence rates of malignant colorectal neoplasms in the no neoplasm (n = 8,967) and benign neoplasm groups (n = 6,438) were 1.81% and 2.55%, respectively ( p < 0.005). A lower 5-yr malignancy rate was observed in benign neoplasm group with polypectomy (2.17%) compared to the benign neoplasm group without polypectomy (3.18%) ( p < 0.05). CONCLUSION: The high recurrence rate of benign colorectal neoplasms and a higher incidence of colorectal cancer in subjects at high risk (history of benign colorectal neoplasm) highlight a healthcare opportunity for surveillance and/or interventions to reduce the morbidity associated with colorectal neoplasms.

Recurrence and malignancy rates in a benign colorectal neoplasm patient cohort: results of a 5-year analysis in a managed care environment.

To estimate the apparent recurrence rates of benign neoplasms and the development of malignant colorectal neoplasms over a 5-yr period in a high risk managed care population. Using the CPT and ICD-9 CM codes, a cohort of subjects with benign neoplasms were identified with a colonoscopy in 1992 from a longitudinal claims database (MarketScan). Three groups of subjects (benign neoplasms with polypectomy, benign neoplasms without polypectomy, and no neoplasms) were evaluated. Five-year recurrence rates of benign or new malignant colorectal neoplasms were determined for the baseline benign neoplasms with polypectomy and no neoplasm groups. For the benign neoplasm without polypectomy, only rates for malignancy were evaluated. Of 16,293 subjects at baseline, 39.50% were diagnosed with benign and 5.50% with malignant neoplasms. The 5-yr cumulative incidence of benign neoplasms in subjects without an index neoplasm (n = 8,967) was 7.92% compared to the recurrence of 40.93% in subjects with a benign neoplasm and polypectomy (n = 4,046) at baseline (p < 0.001). The 5-yr cumulative incidence rates of malignant colorectal neoplasms in the no neoplasm (n = 8,967) and benign neoplasm groups (n = 6,438) were 1.81% and 2.55%, respectively (p < 0.005). A lower 5-yr malignancy rate was observed in benign neoplasm group with polypectomy (2.17%) compared to the benign neoplasm group without polypectomy (3.18%) (p < 0.05). The high recurrence rate of benign colorectal neoplasms and a higher incidence of colorectal cancer in subjects at high risk (history of benign colorectal neoplasm) highlight a healthcare opportunity for surveillance and/or interventions to reduce the morbidity associated with colorectal neoplasms.

Risk factors for colorectal cancer in subjects with family history of the disease.

The relationship between lifestyle factors, past medical conditions, daily meal frequency, diet and the risk of 'familial' colorectal cancer has been analysed using data from a case-control study conducted in northern Italy. A total of 1584 colorectal cancer patients and 2879 control subjects were admitted to a network of hospitals in the Greater Milan area and the Pordenone province. The subjects included for analysis were the 112 cases and the 108 control subjects who reported a family history of colorectal cancer in first-degree relatives. Colorectal cancer cases and control subjects with family history were similarly distributed according to sex, age, marital status, years of schooling and social class. Familial colorectal cancer was associated with meal frequency, medical history of diabetes (relative risk, RR = 4.6) and cholelithiasis (RR = 5.2). Significant positive trends of increasing risk with more frequent consumption were observed for pasta (RR = 2.5, for the highest vs the lowest intake tertile), pastries (RR = 2.4), red meat (RR = 2.9), canned meat (RR = 1.9), cheese (RR = 3.5) and butter (RR = 1.9). Significant inverse associations and trends in risk were observed for consumption of poultry (RR = 0.4), tomatoes (RR = 0.2), peppers (RR = 0.3) and lettuce (RR = 0.3). Significant inverse trends in risk with increasing consumption for beta-carotene and ascorbic acid were observed (RR = 0.5 and 0.4 respectively, highest vs lowest intake tertile). These results suggest that risk factors for subjects with a family history of colorectal cancer in first-degree relatives are not appreciably different from recognized risk factors of the disease in the general population.

Suggested screening guidelines for familial colorectal cancer.

Guidelines for screening for colorectal cancer in subjects with a positive family history of the disease, without the use of DNA based screening, are outlined. These suggestions are derived from (a) the experience of screening 644 subjects at an estimated lifetime risk of dying from colorectal cancer of 10% or more, in the St Mark's Family Cancer Clinic, over six years, and (b) a review of published studies, particularly incorporating the experience of the International Collaboration Group on Hereditary Non-polyposis Colorectal Cancer (HNPCC). Selection of subjects for surveillance depends upon the empirical evaluation of their risk of colorectal cancer, based upon family history details, with the exclusion of a diagnosis of familial adenomatous polyposis in the family. When DNA predictive tests for genes predisposing to HNPCC are available, surveillance can be directed at subjects with a germline mutation known to confer an increased genetic risk of colorectal cancer and discontinued in those at lower (or average) risk. In many subjects, however, DNA testing may still not be possible because of the failure to identify a predisposing mutation in an affected subject in their family. Any surveillance protocol can only be evaluated by long term follow up of those subjects in multiple centres.

Incidence of colorectal cancer following adenomatous polyps of the large intestine.

An association between adenomatous polyps of the large bowel and colorectal cancer has been reported, in the absence, however, of population-based estimates of risk. Subjects with histologically confirmed first diagnosis of large-bowel polyps notified to the population-based Cancer Registry of the Swiss Canton of Vaud (about 600,000 inhabitants) during the calendar period 1979-1990 were actively followed up to the end of 1990 for the subsequent occurrence of malignant neoplasms. Among 2,496 individuals with intestinal polyps, followed for a total of 10,310 person-years at risk (6,201 among males and 4,109 among females), 150 malignant neoplasms were registered versus 152 expected. Thus, the standardized incidence ratio (SIR) for all cancers combined was 0.99. A significant excess was observed for colorectal cancer, with 35 cases observed (19 males, 16 females) versus 17.0 expected (SIR = 2.1; 95% CI: 1.5-3.0). There was also an excess, although not significant, for small-bowel cancer (2 cases observed vs. 0.4 expected; SIR = 5.4). In none of the other cancer sites was SIR significantly or appreciably elevated: in subjects with colorectal polyps the SIR was 1.6 for stomach, 1.0 for lung, 0.9 for breast and 1.2 for prostate. The SIR of colorectal cancer was 3.1 in the first year since polyp registration, and declined thereafter to 1.8, in the absence, however, of any further trend with time since diagnosis. The cumulative risk of colorectal cancer in subjects with colorectal polyps was 2% at 5 years and 3% at 10 years. The quantitative estimates of this study are of interest for their population-based nature, and are potentially useful for defining and targeting screening colonoscopy programmes.

Cholecystectomy and colorectal cancer: evidence from a cohort study on diet and cancer.

The association between cholecystectomy and subsequent risk for colorectal carcinoma was investigated in a prospective cohort study on diet and cancer (n = 120,852), which is being conducted in the Netherlands from 1986 onwards among 120,852 men and women, aged 55 to 69. After a follow-up period of 3.3 years, 478 incident cases of colorectal cancer (258 men and 220 women) were identified in the cohort, 64 of whom reported at baseline to have undergone previous gall-bladder surgery (21 men and 43 women). After adjustment for age and familial history of large-bowel cancer, the relative rate (RR) for colorectal cancer in subjects who had undergone cholecystectomy compared with those who had not was 1.81 in men (p = 0.02) and 1.47 in women (p = 0.05). Additional adjustment for parity. Quetelet index, alcohol intake and other dietary variables resulted in a RR of 1.78 in men and 1.51 in women. In women, the highest RR was detected in the right colon (RR = 1.89), whereas in men, no site within the large bowel accounted specifically for the increased relative rate. In both men and women, the rate appeared to increase from approximately 6 years after cholecystectomy onward. According to the TNM stage of the disease, cholecystectomized patients were not detected at an earlier stage than the other patients. It is concluded that in this study the positive association between colorectal cancer and cholecystectomy cannot be explained by detection bias or ascertainment bias and is not confounded by risk factors for gallstone disease or dietary factors.