Impact of adenoma detection on the benefit of faecal testing vs. colonoscopy for colorectal cancer

Colonoscopy quality, as measured by adenoma detection rates, varies widely across providers and is inversely related to patients' post‐colonoscopy cancer risk. This has unknown consequences for the benefits of faecal immunochemical testing (FIT) vs. primary colonoscopy screening for colorectal cancer. Using an established microsimulation model, we predicted the lifetime colorectal cancer incidence and mortality benefits of annual FIT vs. 10‐yearly colonoscopy screening at differing ADR levels (quintiles; averages 15.3–38.7%), with colonoscopy performance assumptions estimated from community‐based data on physician ADRs and patients' post‐colonoscopy risk of cancer. For patients receiving FIT screening with follow‐up colonoscopy by physicians from the highest ADR quintile, simulated lifetime cancer incidence and mortality were 28.8 and 5.4 per 1,000, respectively, vs. 20.6 and 4.4 for primary colonoscopy screening (risk ratios, RR = 1.40; 95% probability interval (PI), 1.19–1.71 for incidence, and RR = 1.22; 95%PI, 1.02–1.54 for mortality). With every 5% point ADR decrease, lifetime cancer incidence was predicted to increase on average 9.0% for FIT vs. 12.3% for colonoscopy, and mortality increased 9.9% vs. 13.3%. In ADR quintile 1, simulated mortality was lower for FIT than colonoscopy screening (10.1 vs. 11.8; RR = 0.85; 95%PI, 0.83–0.90), while incidences were more similar. This suggests that relative cancer incidence and mortality reductions for FIT vs. colonoscopy screening may differ by ADR, with fewer predicted deaths with colonoscopy screening in higher ADR settings and fewer deaths with annual FIT screening in lower ADR settings.     

Long‐term risk of colorectal cancer after negative colonoscopy in a Danish gFOBT screening cohort

Faecal occult blood test (FOBT) screening for colorectal cancer (CRC) is implemented in several countries. Approximately half of all screen positive persons have negative colonoscopy, but consensus is lacking on how these persons should be followed up. Health authorities in Denmark and The Netherlands recommend suspending screening for 8–10 years, while patients in UK are invited to screening after 2 years. In this cohort‐study, we followed 166,277 individuals invited to FOBT‐screening in 2005–2006 and a reference group comprising the remaining 1,240,348 Danes of the same age. We linked Danish population and health service registers to obtain information about colonoscopy outcome and incident CRC. We estimated CRC risk by colonoscopy outcome (adenoma, other colorectal pathology or negative colonoscopy) for the reference group, the screening group, and subgroups. Persons with positive screening FOBT followed by negative colonoscopy had the same long‐term CRC risk as persons with adenoma detected due to a positive screening FOBT (aHR 1.33, 95% CI: 0.65–2.71). We found no difference in the long‐term CRC risk between persons with negative colonoscopy after a positive FOBT screening test and the unscreened reference population (aHR 1.05, 95% CI: 0.62–1.78). Since FOBT screen positive persons in our study remained at average risk of CRC despite of a negative index colonoscopy, we question the safety of suspending FOBT screening for this group. It needs to be monitored whether recent efforts to improve colonoscopy quality have been successful in ensuring low CRC risk after negative colonoscopy also in FOBT positive persons.     

Dietary patterns during high school and risk of colorectal adenoma in a cohort of middle‐aged women

Adolescent diet may be etiologically relevant for later risk of colorectal adenoma, a precursor of colorectal cancer. We aimed to examine associations between adolescent dietary patterns (derived using factor analysis) and risk of colorectal adenoma in middle adulthood. We analyzed data from 17,221 women participating in the Nurses' Health Study II, who had completed a validated high school (HS) food frequency questionnaire in 1998 when they were 34–51 years old, and had subsequently undergone at least one lower bowel endoscopy. Between 1998 and 2007, 1,299 women were diagnosed with at least one colorectal adenoma. In multivariable models adjusted for adult dietary patterns, a higher “prudent” pattern during HS, characterized by high consumption of vegetables, fruit and fish was associated with a statistically significantly lower risk of rectal (odds ratio [OR] highest vs. lowest quintile, 0.45, 95% CI 0.27–0.75, p‐trend = 0.005), but not colon adenomas. A higher “Western” pattern during HS, characterized by high consumption of desserts and sweets, snack foods and red and processed meat, was significantly associated with rectal (OR 1.78, 95% CI 1.12–2.85, p‐trend = 0.005) and advanced (OR 1.58, 95% CI 1.07–2.33, p‐trend = 0.08), but not associated with colon or non‐advanced adenomas. This study suggests that overall eating patterns during high school may influence later risk of rectal and advanced adenoma, independent of adult diet. Our results support the hypothesis that diet during early life may influence colorectal carcinogenesis.     

Family history of colorectal cancer: A determinant of advanced adenoma stage or adenoma multiplicity?

A family history of colorectal cancer may increase colorectal cancer risk by influencing adenoma growth or enhancing the formation of new lesions. Data of men from the prospective Health Professionals Follow‐Up Study who underwent an endoscopy between 1986 and 2004 were used to evaluate whether a family history of colorectal cancer is associated with adenoma multiplicity or advanced adenoma stage (≥1 cm, histology with villous component or carcinoma in situ). 21.4% of the 3,881 adenoma patients and 13.9% of the 24,959 adenoma‐free men had a first‐degree relative with colorectal cancer. Thousand four hundred and ninety‐six men were classified as having advanced and 1,507 as having nonadvanced adenomas. Six hundred and twenty‐two men had multiple and 1,985 had single adenomas in the distal colon and rectum. A family history of colorectal cancer was similarly associated with advanced and nonadvanced adenomas [multivariable odds ratio (OR) (95% confidence interval): advanced vs. nonadvanced, 0.98 (0.82–1.17), advanced vs. adenoma‐free: 1.67 (1.47–1.91), nonadvanced vs. adenoma‐free: 1.70 (1.49–1.94)], although potential differences according to adenoma location were seen. A family history of colorectal cancer was more strongly associated with multiple distally located adenomas [odds ratio (95% confidence interval): multiple vs. single, 1.35 (1.09–1.68), multiple vs. no distally located adenomas: 2.02 (1.67–2.44), single vs. no distally located adenomas: 1.49 (1.32–1.68)]. The number of adenomas was also positively associated with a family history of colorectal cancer. Our findings suggest that at the population level, heritable factors may be more important in earlier stages of adenoma formation than at stages of adenoma advancement for at least distally located adenomas. © 2009 UICC     

Men with negative results of guaiac‐based fecal occult blood test have higher prevalences of colorectal neoplasms than women with positive results

Guaiac‐based fecal occult blood tests (gFOBTs) are the most commonly applied tests for colorectal cancer screening globally but have relatively poor sensitivity to detect colorectal neoplasms. Men have higher prevalences of colorectal neoplasms than women. In case of a positive gFOBT result, participants are referred to colonoscopy, independent of sex. To assess performance of gFOBT in routine screening practice, we assessed age and sex specific prevalences (age groups: 55–59, 60–64, 65–69 and 70–74) of colorectal neoplasms in 182,956 women and men undergoing colonoscopy for primary screening and in 20,884 women and men undergoing colonoscopy to follow‐up a positive gFOBT in Bavaria, Germany, in 2007–2009. We conducted model calculations to estimate prevalences among gFOBT negative individuals. Analogous model calculations were performed for women and men tested positive or negative with fecal immunochemical tests. In all age groups (55–59, 60–64, 65–69 and 70–74 years), men undergoing colonoscopy for primary screening had substantially higher prevalences of any colorectal neoplasms and essentially the same prevalences of advanced colorectal neoplasms compared to women undergoing colonoscopy to follow‐up a positive gFOBT. Model calculations suggest that men with negative gFOBT likewise have substantially higher prevalences of colorectal neoplasms than gFOBT positive women in each age group. Model calculations further indicate that no such sex paradoxon occurs, and a much clearer risk stratification can be achieved with fecal immunochemical tests. Our findings underline need to move forward from and overcome shortcomings of gFOBT‐based colorectal cancer screening.     

Visceral abdominal fat measured by computed tomography is associated with an increased risk of colorectal adenoma

We investigated whether visceral adipose tissue (VAT) measured by computed tomography (CT) is a risk factor for colorectal adenoma. For a total of 1,328 patients (857 without adenoma, 471 with colorectal adenoma) undergoing colonoscopy and CT, associations between colorectal adenoma and body mass index (BMI), VAT area and subcutaneous adipose tissue (SAT) were assessed using odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for age, sex, family history, smoking, alcohol intake, diabetes mellitus, aspirin use and nonsteroidal anti‐inflammatory drug use. Multivariate analysis showed that colorectal adenoma was marginally associated (p = 0.06) with BMI, but not with SAT, while it was significantly associated with VAT and the VAT to SAT ratio (VAT/SAT) for both categorical data and trend (p < 0.05). When the obesity indices were considered simultaneously, colorectal adenoma remained significantly associated with VAT and VAT/SAT (p < 0.05), but not BMI and SAT. In patients with colorectal adenoma, the adjusted OR for the highest quartiles of VAT and VAT/SAT was 1.90 (95% CI 1.16–3.13) and 2.25 (95% CI 1.49–3.41), respectively, compared to the lowest quartiles. Only VAT area was significantly associated with colorectal adenoma in both men and women (p < 0.05). Proximal, multiple and advanced adenomas had significantly higher VAT areas (p < 0.05) than distal, solitary and nonadvanced adenomas. Our findings implicate abdominal VAT in the development and progression of colorectal adenoma, and it was better obesity index for colorectal adenoma than BMI in both sexes.     

Red and processed meat intake and cancer risk: Results from the prospective NutriNet‐Santé cohort study

The International Agency for Research on Cancer (WHO‐IARC) classified red meat and processed meat as probably carcinogenic and carcinogenic for humans, respectively. These conclusions were mainly based on studies concerning colorectal cancer, but scientific evidence is still limited for other cancer locations. In this study, we investigated the prospective associations between red and processed meat intakes and overall, breast, and prostate cancer risk. This prospective study included 61,476 men and women of the French NutriNet‐Santé cohort (2009–2015) aged ≥35 y and who completed at least three 24 hrs dietary records during the first year of follow‐up. The risk of developing cancer was compared across sex‐specific quintiles of red and processed meat intakes by multivariable Cox models. 1,609 first primary incident cancer cases were diagnosed during follow‐up, among which 544 breast cancers and 222 prostate cancers. Red meat intake was associated with increased risk of overall cancers [HR_Q5vs.Q1=1.31 (1.10–1.55), p_trend = 0.01) and breast cancer (HR_Q5vs.Q1 = 1.83 (1.33–2.51), p_trend = 0.002]. The latter association was observed in both premenopausal [HR_Q5vs.Q1=2.04 (1.03–4.06)] and postmenopausal women [HR_Q5vs.Q1=1.79 (1.26‐2.55)]. No association was observed between red meat intake and prostate cancer risk. Processed meat intake was relatively low in this study (cut‐offs for the 5th quintile = 46 g/d in men and 29 g/d in women) and was not associated with overall, breast or prostate cancer risk. This large cohort study suggested that red meat may be involved carcinogenesis at several cancer locations (other than colon‐rectum), in particular breast cancer. These results are consistent with mechanistic evidence from experimental studies.     

Stratifying HPV‐positive women for CIN3+ risk after one and two rounds of HPV‐based screening

A main challenge of human papilloma (HPV)‐based screening for cervical cancer is to adequately identify HPV‐positive women at highest risk of cervical intraepithelial neoplasia grade 3 or worse, CIN3+. The prognostic value of currently used adjunct markers (HPV16/18 genotyping and reflex cytology) may change after multiple rounds of HPV‐based screening because of a change in the proportion of HPV‐positive women with incident infections. To this end, we re‐analyzed results from the POBASCAM trial (Population Based Screening Study Amsterdam). Women were randomized to HPV/cytology cotesting (intervention group) or to cytology‐only (HPV blinded; control group) at enrolment. Our analytical population consisted of women with an HPV‐positive result at the second round, 5 years after enrolment (n = 381 intervention, n = 392 control). Nine‐year CIN3+ risks were estimated by Kaplan–Meier. HPV‐positive women were stratified by risk markers: HPV16/18 genotyping, reflex cytology and preceding HPV results. When comparing one to two rounds of HPV‐based screening, the prognostic value of an abnormal cytology result did not change (40.0% vs. 42.3%, p = 0.5617), but diminished for an HPV16/18 positive result (25.4% vs. 38.0%, p = 0.0132). HPV16/18 genotyping was nondiscriminative in women with incident HPV infections (HPV16/18 positive 10.0% vs. negative 12.1%, p = 0.3193). Women from the intervention group were more likely to have incident infections compared to women from the control group (incident screen‐positive results 75.6% vs. 64.6%, p = 0.001) Our results indicate that at a second round of HPV‐based screening, risk differentiation by cytology remained strong, but was diminished for HPV 16/18 genotyping because of a larger proportion of incident infections.     

Non‐steroidal anti‐inflammatory drugs and cancer risk in women: Results from the Women's Health Initiative

The use of non‐steroidal anti‐inflammatory drugs (NSAIDs) has been associated with reduced risks of cancers at several sites in some studies; however, we recently reported no association between their use and total cancer risk in women in a prospective study. Here we examine the association between NSAIDs and total and site‐specific cancer incidence in the large, prospective Women's Health Initiative (WHI). Women (129,013) were recruited to participate in the WHI at 40 US clinical centers from 1993 to 1998 and followed prospectively. After 9.7 years of follow‐up, 12,998 incident, first primary, invasive cancers were diagnosed. NSAID use was systematically collected at study visits. We used Cox proportional hazards regression models to estimate multivariable‐adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between NSAIDs use and total and site‐specific cancer risk. Relative to non‐use, consistent use (i.e., use at baseline and year 3 of follow‐up) of any NSAID was not associated with total cancer risk (HR 1.00, 95% CI: 0.94–1.06). Results for individual NSAIDs were similar to the aggregate measure. In site‐specific analyses, NSAIDs were associated with reduced risks of colorectal cancer, ovarian cancer, and melanoma. Our study confirms a chemopreventive benefit for colorectal cancer in women and gives preliminary evidence for a reduction of the risk of some rarer cancers. NSAIDs' benefit on cancer risk was therefore limited to specific sites and not evident when total cancer risk was examined. This information may be of importance when NSAIDs are considered as chemopreventive agents.     

Clinico-Epidemiologic Study of the Metabolic Syndrome and Lifestyle Factors Associated with the Risk of Colon Adenoma and Adenocarcinoma

Background: The numbers of patients with colorectal cancer and associated deaths have been increasing in Japan, probably due to rapid lifestyle changes. Prevention is clearly important and the present study aimed to clarify risk factors and to promote colon cancer screening. Methods: We investigated lifestyle factors, biochemical data, and pathological features of 727 individuals who underwent colonoscopy. Data were subjected to statistical analysis using SPSS software. Results: Low-grade adenoma was more frequent among the elderly and in men. All of the men and 87.5% of the women with high-grade adenoma or adenocarcinoma were aged ≥45 and ≥50 years, respectively. In women, a larger waist circumference (≥80 cm) increased the odds ratio for colon adenoma or adenocarcinoma (colon tumors) by 1.033 (95% confidence index (CI), 1.001-1.066; p=0.040). Metabolic syndrome significantly increased the odds ratio of colon tumors in men, but not in women. Cigarette smoking, drinking alcohol, and increased physical activity were significant risk factors for colon tumors in men, with odds ratios of 1.001 (95% CI, 1.000-1.002; p=0.001), 1.001 (95% CI, 1.000-1.003; p=0.047), and 1.406 (95% CI 1.038-1.904; p=0.028), respectively. Conclusions: Colon tumors have a high prevalence in the elderly. A larger waist circumference in women and metabolic syndrome in both men and women elevate the risk of colon tumors. In addition, smoking, drinking, and excessive physical activity are risk factors for adenoma and adenocarcinoma in men. For early detection of colorectal cancer, men older than 45 years and women older than 50 years with these risk factors are recommended to undergo colonoscopy.     

Dietary isoflavone and the risk of colorectal adenoma: a case�Ccontrol study in Japan

We conducted a case–control study in a Japanese population to investigate the association between dietary isoflavone intake and the risk of colorectal adenoma. Participants who underwent magnifying colonoscopy with dye spreading as part of a cancer screening programme responded to a self-administered questionnaire, which included lifestyle information and intake of 145 food items, before the colonoscopy. A total of 721 case and 697 control subjects were enrolled. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. We found a significant inverse association between dietary isoflavone intake and the risk of colorectal adenoma in men and women combined. However, the inverse association was not linear; rather, all quartiles above the first showed a similar decrease in risk, with multivariable-adjusted ORs and 95% CIs compared with the lowest quartile of 0.77 (0.57–1.04), 0.76 (0.56–1.02) and 0.70 (0.51–0.96) in the second, third and highest quartiles, respectively (P for trend=0.03). Of interest, the observed association was more prominent in women than in men. The observed ceiling effect associated with higher isoflavone intake suggests that a lower intake of dietary isoflavone might be associated with an increased risk of colorectal adenoma in Japanese populations.     

Meat consumption and colorectal cancer risk in Japan: The Takayama study

Compared with the abundant data from Western countries, evidence regarding meat consumption and colorectal cancer is limited in the Japanese population. We evaluated colorectal cancer risk in relation to meat consumption in a population‐based prospective cohort study in Japan. Participants were 13 957 men and 16 374 women aged ≥35 years in September 1992. Meat intake, assessed with a validated food frequency questionnaire, was controlled for the total energy intake. The incidence of colorectal cancer was confirmed through regional population‐based cancer registries and histological identification from colonoscopy in two main hospitals in the study area. From September 1992 to March 2008, 429 men and 343 women developed colorectal cancer. After adjustments for multiple confounders, a significantly increased relative risk of colorectal cancer was observed in the highest versus lowest quartile of the intake of total and red meat among men; the estimated hazard ratios were 1.36 (95% CI: 1.03, 1.79) for total meat (P for trend = 0.022), and 1.44 (95% CI: 1.10, 1.89) for red meat (P for trend = 0.009). A positive association between processed meat intake and colon cancer risk was also observed in men. There was no significant association between colorectal cancer and meat consumption in women. These results suggest that the intake of red and processed meat increases the risk of colorectal or colon cancer among Japanese men. Abstaining from excessive consumption of meat might be protective against developing colorectal cancer.     

Fruit and vegetable intakes and risk of colorectal cancer and incident and recurrent adenomas in the PLCO cancer screening trial

The roles of fruits and vegetables in colorectal cancer development are unclear. Few prospective studies have assessed the association with adenoma, a known precursor to colorectal cancer. Our aim was to evaluate the association between fruit and vegetable intake and colorectal cancer development by evaluating the risk of incident and recurrent colorectal adenoma and colorectal cancer. Study participants were identified from the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Fruit and vegetable intake was measured using a self‐reported dietary questionnaire. Total fruit and vegetable intake was not associated with reduced incident or recurrent adenoma risk overall, but a protective association was observed for multiple adenomas (Odds ratio _{3rd tertile vs. 1st tertile} = 0.61, 95% confidence interval (CI): 0.38, 1.00). Higher fruit and vegetable intakes were associated with a borderline reduced risk of colorectal cancer (Hazard ratio (HR) _{3rd tertile vs. 1st tertile} = 0.82, 95% CI: 0.67, 1.01), which reached significance amongst individuals with high processed meat intakes (HR = 0.74, 95% CI: 0.55, 0.99). Our results suggest that increased fruit and vegetable intake may protect against multiple adenoma development and may reduce the detrimental effects of high processed meat intakes on colorectal cancer risk.     

Detection of colorectal neoplasia: Combination of eight blood‐based,cancer‐associated protein biomarkers

Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer‐associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19‐9, CEA, hs‐CRP, CyFra21‐1, Ferritin, Galectin‐3 and TIMP‐1 were determined in EDTA‐plasma using the Abbott ARCHITECT® automated immunoassay platform. Primary endpoints were detection of (i) CRC and high‐risk adenoma and (ii) CRC. Logistic regression was performed. Final reduced models were constructed selecting the four biomarkers with the highest likelihood scores. Subjects (N = 4,698) were consecutively included during 2010–2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer and 193 rectal cancer. Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high‐risk, 1,342 had nonneoplastic bowell disease and 1,978 subjects had ‘clean’ colorectum. Univariable analysis demonstrated that all biomarkers were statistically significant. Multivariate logistic regression demonstrated that the blood‐based biomarkers in combination significantly predicted the endpoints. The reduced model resulted in the selection of CEA, hs‐CRP, CyFra21‐1 and Ferritin for the two endpoints; AUCs were 0.76 and 0.84, respectively. The postive predictive value at 90% sensitivity was 25% for endpoint 1 and the negative predictive value was 93%. For endpoint 2, the postive predictive value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC.     

Strong subsite‐specific variation in detecting advanced adenomas by fecal immunochemical testing for hemoglobin

Fecal immunochemical tests (FITs) for hemoglobin are increasingly recommended and used in colorectal cancer (CRC) screening. We aimed to provide a detailed assessment of the sensitivity of FIT according to type and subsite of neoplasms in a true screening setting. A quantitative FIT (FOB Gold, Sentinel Diagnostics, Milano, Italy) was applied prior to colonoscopy by 3,466 participants of the German screening colonoscopy program. Subsite specific sensitivity for various types of colorectal neoplasms was derived by comparing FIT results with findings at screening colonoscopy. The most advanced finding at colonoscopy was CRC, advanced adenoma, and nonadvanced adenoma in 29, 354 and 686 cases, respectively. Per‐adenoma sensitivity for large advanced adenomas (>1 cm) strongly varied by location (p < 0.001): cecum: 0/14 (0%), ascending colon and right flexure: 11/43 (26%), transverse colon and left flexure: 2/14 (14%), descending colon: 7/12 (58%), sigmoid colon: 47/92 (51%), rectum: 14/39 (36%). By contrast, the FIT detected all of 5 proximal CRC and 23 out of 24 (96%) distal CRCs, whereas per‐adenoma sensitivity of both proximal (17/259, 7%) and distal nonadvanced adenomas (20/237, 8%) essentially equaled the false positivity rate among those without neoplasms (152/2,397, 6%). In conclusion, we found a very large gradient of subsite specific FIT sensitivity for detecting large advanced adenomas ranging from 0% for advanced adenomas located in the cecum to >50% for those located in the descending or sigmoid colon. By contrast, FIT sensitivity was uniformly excellent for CRC and uniformly poor for nonadvanced adenomas, regardless of their location.     

初查结肠镜阴性人群结直肠肿瘤发生风险研究

目的 调查初查结肠镜结果阴性人群再次进行结肠镜检查情况,探讨不同性别、年龄、风险等级人群在不同时间间隔结直肠肿瘤的发生风险.方法 采用双向性队列研究设计,利用自制调查表对1995年1月1日至2005年12月31日在长海医院初查结肠镜结果阴性无症状平均风险人群进行电话随访.调查内容包括初次结肠镜检查以后所有结肠镜检查情况、结直肠癌危险分层相关因素（年龄、性别、吸烟情况、糖尿病病史、绿色蔬菜摄人情况、腌制食品摄人情况、油炸熏制食品摄人情况、白肉摄人情况）等.采用寿命表生存分析法研究不同性别、年龄、风险等级人群发生结直肠肿瘤的累积风险.结果 共纳入455例研究对象,有91例发生息肉病变,24例发生腺瘤病变,9例发生进展期肿瘤病变,初查结肠镜阴性人群5年后结直肠息肉、腺瘤、进展期肿瘤的累积发生率分别为11.9％、4.2％和2.0％.12年进展期肿瘤的累积发生率为3.9％.男性发生息肉病变的风险高于女性（x2=8.142,P=0.004）;年龄≥60岁人群发生息肉病变的风险高于年龄＜60岁人群（x2=6.321,P=0.012）;高风险组人群发生息肉病变的风险高于低风险组人群（x2=4.082,P=0.043）.结论 对于初查结肠镜结果阴性人群,结直肠息肉、腺瘤、进展期肿瘤5年的累积发生率均较低,12年内发生进展期肿瘤的风险也较低.     

Leptin concentrations, leptin receptor polymorphisms, and colorectal adenoma risk.

Obesity has been shown to be associated with an increased risk of both colorectal cancer and adenomatous polyps. One mechanism underlying this relationship may involve the growth-promoting effects of the circulating hormones associated with obesity, such as leptin. We conducted a gastroenterology clinic-based, case-control study to evaluate the relationship between circulating leptin concentrations and colorectal adenoma risk; in addition, we evaluated the relationship between leptin receptor polymorphisms and adenoma risk. Individuals with adenomas (n = 157) and colonoscopy-negative controls (n = 191), who had a clinically indicated colonoscopy, were recruited from a large health maintenance organization in the Seattle metropolitan area from 1999 to 2003. Odds ratios and 95% confidence intervals were obtained using logistic regression, adjusting for age at diagnosis, body mass index, family history of colorectal cancer, smoking history, nonsteroidal anti-inflammatory drug use, physical activity, and, among women, menopausal status and postmenopausal hormone use. Among men, those in the highest tertile of leptin concentrations had a 3.3-fold (95% confidence interval, 1.2-8.7) increased adenoma risk compared with those in the lowest tertile (P trend = 0.01). There were no associations between leptin concentrations and adenoma risk in women. There were no associations of leptin receptor genotypes or haplotypes and adenoma risk. The results of this study suggest that, in men, leptin may be associated with risk of colorectal adenomas.     

Change in body size and the risk of colorectal adenomas.

Adiposity has been recognized as a risk factor for colorectal adenoma, but the influence of weight gain, adipose tissue distribution, and possible differences between ethnic/racial and gender groups remains unanswered. The aim of this prospective study was to examine the association between adiposity and weight change and colorectal adenoma risk. Over approximately 10-year period, anthropometric measures and other risk factors were measured at three time points in the multicenter multiethnic Insulin Resistance Atherosclerosis Study cohort. Colonoscopies were then conducted on 600 cohort participants regardless of symptoms whose mean age at colonoscopy was 64 years. Multivariate logistic regression analyses were used to assess the association between colorectal adenomas and measures of adiposity and weight change over the approximately 10-year period before colonoscopy. Obesity was positively associated with risk of colorectal adenomas at the time of colonoscopy [adjusted odds ratio (OR(adj)), 2.16; 95% confidence interval (95% CI), 1.13-4.14] and was stronger in women (OR(adj), 4.42; 95% CI, 1.53-12.78) than in men (OR(adj), 1.26; 95% CI, 0.52-3.07). The risk of adenomas increased among participants who gained weight compared with those who maintained weight over the approximately 5 years (OR(adj), 2.30; 95% CI, 1.25-4.22) and approximately 10 years (OR(adj), 2.12; 95% CI, 1.25-3.62). These associations were similar for both advanced and nonadvanced adenomas. These results suggest a positive association between obesity, weight gain, and colorectal adenoma risk. Stronger associations were observed when obesity was measured at the time of colonoscopy, suggesting that obesity may be a promoting factor in the growth of colorectal adenomas.     

A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women.

Insulin-like growth factor-1 (IGF-1) is an important mitogen, and IGF binding protein-3 (IGFBP-3) has opposing effects. Acromegalics, who have abnormally elevated levels of IGF-1, are at increased risk of colorectal tumors. Recent studies have found that IGF-1 levels correlate with risk of prostate cancer and colorectal cancer in men, premenopausal breast cancer in women, and lung cancer in men and women. We examined whether prediagnostic plasma levels of IGF-1 and IGFBP-3 influence risk of colorectal cancer and adenoma in women. From 1989 to 1990, a total of 32,826 women from the Nurses' Health Study provided blood specimens that were archived in liquid nitrogen. During 6 years of follow-up from 1989 to 1994, we documented 79 new cases of colorectal cancer, 90 cases of intermediate/late-stage adenoma (> or =1 cm or tubulovillous/villous histology), and 107 cases of early-stage adenoma (<1 cm and tubular histology). After matching controls (2:1 for cancers and 1:1 for adenomas) to cases by age, month of blood draw, fasting status, and indication for endoscopy (for adenoma controls), plasma IGF-1 and IGFBP-3 levels were measured. Controlling for IGFBP-3 level, relative to women in the low tertile of IGF-1, those in the high tertile were at elevated risk of intermediate/late-stage colorectal neoplasia adenoma [multivariate relative risk (RR), 2.78; 95% confidence interval (CI), 0.76-9.76] and cancer (RR, 2.18; 95% CI, 0.94-5.08). Controlling for IGF-1 level, relative to women in the low tertile of IGFBP-3, women in the high tertile of IGFBP-3 were at lower risk of intermediate/late-stage colorectal adenoma (RR, 0.28; 95% CI, 0.09-0.85) and cancer (RR, 0.28; 95% CI, 0.10-0.83). Neither IGF-1 nor IGFBP-3 had any appreciable relation with early-stage adenoma. These analyses indicate that high levels of circulating IGF-1 and particularly low levels of IGFBP-3 are associated independently with an elevated risk of large or tubulovillous/villous colorectal adenoma and cancer.     

Calcium,vitamin D,dairy products,and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort (United States)

Objective: Calcium, vitamin D, and dairy product intake may reduce the risk of colorectal cancer. We therefore examined the association between these factors and risk of colorectal cancer in a large prospective cohort of United States men and women. Methods: Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed questionnaire on diet, medical history, and lifestyle in 1992–93. After excluding participants with a history of cancer or incomplete dietary information, 60,866 men and 66,883 women remained for analysis. During follow-up through 31 August 1997 we documented 421 and 262 cases of incident colorectal cancers among men and women, respectively. Multivariate-adjusted rate ratios (RR) were calculated using Cox proportional hazards models. Results: Total calcium intake (from diet and supplements) was associated with marginally lower colorectal cancer risk in men and women (RR = 0.87, 95% CI 0.67–1.12, highest vs lowest quintiles, p trend = 0.02). The association was strongest for calcium from supplements (RR = 0.69, 95% CI 0.49–0.96 for 500 mg/day vs none). Total vitamin D intake (from diet and multivitamins) was also inversely associated with risk of colorectal cancer, particularly among men (RR = 0.71, 95% CI 0.51–0.98, p trend = 0.02). Dairy product intake was not related to overall risk. Conclusions: Our results support the hypothesis that calcium modestly reduces risk of colorectal cancer. Vitamin D was associated with reduced risk of colorectal cancer only in men.