A Comparative Case-Control Study of Colorectal Cancer and Adenoma

We conducted a comparative case-control study of colorectal cancer and adenoma involving 221 cases with colorectal cancer, 525 cases with colorectal adenoma and 578 neighborhood controls. Daily vegetables intake was associated with lower risks of distal colon adenoma (relative risk (RR)=0.59, 95% confidence interval (CI): 0.39–0.89) and rectal cancer (RR=0.46, 95% CI: 0.25–0.84). Daily beans intake was associated with lower risk of colon adenoma (RR=0.58, 95% CI: 0.37–0.91 for the proximal colon and RR=0.63, 95% CI: 0.45–0.88 for the distal colon) and daily intake of seaweeds was associated with lower risk of rectal cancer (RR=0.42, 95% CI: 0.22–0.82). Daily intake of fish and shellfish also showed an inverse association with the risk of colon adenoma (RR=0.67, 95% CI: 0.45–0.99 for the proximal colon and RR=0.70, 95% CI: 0.52–0.94 for the distal colon). Generally, intakes of animal or vegetable fat-rich foods, especially meats, were associated with decreases in risks of both adenoma and cancer, though the association of cancer was not statistically significant. Other than dietary factors, daily alcohol drinking was associated with an increased risk of adenoma in the proximal colon (RR=1.95, 95% CI: 1.15–3.29) and ex-drinkers showed higher risks for colon adenoma and colorectal cancer. Sports or occupational activities and coffee drinking were inversely associated and family history of colorectal cancer was positively associated with the risks of both colorectal adenoma and cancer.     

A case-control study of male colorectal cancer in Aichi Prefecture, Japan: with special reference to occupational activity level, drinking habits and family history

The relationships of occupational activity level, drinking habits and family history of cancer to the risk of male colorectal cancer by subsites were investigated in a case-control study involving 1,716 cases with colon cancer, 1,611 cases with rectal cancer and 16,600 controls with other sites of cancer identified from the Aichi Cancer Registry, Japan 1979-1987. An occupation with a low activity level was associated with an increased risk of colorectal cancer; the age-adjusted relative risk (RR) compared to the high activity level group was 1.92 (95% confidence interval (CI): 1.38-2.67) for proximal colon cancer, 1.52 (95% CI: 1.19-1.94) for distal colon cancer and 1.38 (95% CI: 1.17-1.62) for rectal cancer. Beer drinkers showed an increased risk of colorectal cancer; the age-adjusted RR was 1.49 (95% CI: 1.13-1.95) for proximal colon cancer, 1.65 (95% CI: 1.34-2.04) for distal colon cancer and 1.88 (95% CI: 1.62-2.18) for rectal cancer. The RR for family history of colorectal cancer was 3.40 (95% CI: 2.19-5.29) for proximal colon cancer, 2.54 (95% CI: 1.73-3.75) for distal colon cancer and 1.78 (95% CI: 1.28-2.49) for rectal cancer. Multivariate analysis controlled for age, residence, marital status and smoking in addition to occupational activity level, beer drinking and family history of colorectal cancer did not materially change the RRs. When these three variables were combined, the RR was 15.72 (95% CI: 5.40-45.78) for proximal colon cancer, 10.55 (95% CI: 4.24-26.27) for distal colon cancer and 6.69 (95% CI: 3.12-14.36) for rectal cancer.     

A Case-Control Study of Male Colorectal Cancer in Aichi Prefecture, Japan: with Special Reference to Occupational Activity Level, Drinking Habits and Family History

The relationships of occupational activity level, drinking habits and family history of cancer to the risk of male colorectal cancer by subsites were investigated in a case-control study involving 1,716 cases with colon cancer, 1,611 cases with rectal cancer and 16,600 controls with other sites of cancer identified from the Aichi Cancer Registry, Japan 1979–1987. An occupation with a low activity level was associated with an increased risk of colorectal cancer; the age-adjusted relative risk (RR) compared to the high activity level group was 1.92 (95% confidence interval (CI): 1.38–2.67) for proximal colon cancer, 1.52 (95% CI: 1.19–1.94) for distal colon cancer and 1.38 (95% CI: 1.17–1.62) for rectal cancer. Beer drinkers showed an increased risk of colorectal cancer; the age-adjusted RR was 1.49 (95% CI: 1.13–1.95) for proximal colon cancer, 1.65 (95% CI: 1.34-2.04) for distal colon cancer and 1.88 (95% CI: 1.62–2.18) for rectal cancer. The RR for family history of colorectal cancer was 3.40 (95% CI: 2.19–5.29) for proximal colon cancer, 2.54 (95% CI: 1.73–3.75) for distal colon cancer and 1.78 (95% CI: 1.28–2.49) for rectal cancer. Multivariate analysis controlled for age, residence, marital status and smoking in addition to occupational activity level, beer drinking and family history of colorectal cancer did not materially change the RRs. When these three variables were combined, the RR was 15.72 (95% CI: 5.40–45.78) for proximal colon cancer, 10.55 (95% CI: 4.24–26.27) for distal colon cancer and 6.69 (95% CI: 3.12–14.36) for rectal cancer.     

Dietary marine n-3 fatty acids in relation to risk of distal colorectal adenoma in women.

Epidemiologic studies of dietary marine n-3 fatty acids and risk of colorectal cancer have been inconsistent, and their relation to risk of colorectal adenoma has not been evaluated in detail. We examined dietary marine n-3 fatty acids and the ratio of marine n-3 to total n-6 fatty acids (n-3/n-6 ratio) in relation to risk of adenoma of the distal colon or rectum among 34,451 U.S. women who were initially free of colorectal cancer or polyps, who completed a semiquantitative food frequency questionnaire in 1980, and who underwent endoscopy from 1980 to 1998. We documented 1,719 distal colorectal adenoma cases (705 large adenomas, 897 small adenomas, 1,280 distal colon adenomas, and 505 rectal adenomas) during 18 years of follow-up. Neither dietary marine n-3 fatty acids nor n-3/n-6 ratio were associated with risk of total distal colorectal adenoma after adjustment for age and established risk factors [multivariable relative risk (RR) for extreme quintiles of dietary marine n-3 fatty acids = 1.04; 95% confidence interval (95% CI), 0.84-1.27, P(trend) = 0.66; RR for extreme quintiles of n-3/n-6 ratio = 1.02; 95% CI, 0.83-1.25; P(trend) = 0.86]. Similarly, no significant associations were observed separately for distal colon or rectal adenoma. However, higher intake of dietary marine n-3 fatty acids was nonsignificantly but suggestively inversely associated with large adenoma (RR, 0.74; 95% CI, 0.54-1.01; P(trend) = 0.16) but directly associated with small adenoma (RR, 1.36; 95% CI, 1.02-1.81; P(trend) = 0.09). Our findings do not support the hypothesis that a higher intake of marine n-3 fatty acids or a higher n-3/n-6 ratio reduces the risk of distal colorectal adenoma but are suggestive that higher intake may reduce the progression of small adenomas to large adenomas.     

Calcium intake and risk of colon cancer in women and men

BACKGROUND: Calcium has been hypothesized to reduce the risk of colon cancer, and in a recent randomized trial, calcium supplementation was associated with reduction in the risk of recurrent colorectal adenomas. We examined the association between calcium intake and colon cancer risk in two prospective cohorts, the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). METHODS: Our study population included 87 998 women in NHS and 47 344 men in HPFS who, at baseline (1980 for NHS and 1986 for HPFS), completed a food frequency questionnaire and provided information on medical history and lifestyle factors. Dietary information was updated at least every 4 years. During the follow-up period (1980 to May 31, 1996 for the NHS cohort; 1986 to January 31, 1996 for the HPFS cohort), 626 and 399 colon cancer cases were identified in women and men, respectively. Pooled logistic regression was used to estimate relative risks (RRs), and all statistical tests were two-sided. RESULTS: In women and men considered together, we found an inverse association between higher total calcium intake (>1250 mg/day versus < or =500 mg/day) and distal colon cancer (women: multivariate RR = 0.73, 95% confidence interval [CI] = 0.41 to 1.27; men: RR = 0.58, 95% CI = 0.32 to 1.05; pooled RR = 0.65, 95% CI = 0.43 to 0.98). No such association was found for proximal colon cancer (women: RR = 1.28, 95% CI = 0.75 to 2.16; men: RR = 0.92, 95% CI = 0.45 to 1.87; pooled RR = 1.14, 95% CI = 0.72 to 1.81). The incremental benefit of additional calcium intake beyond approximately 700 mg/day appeared to be minimal. CONCLUSIONS: Higher calcium intake is associated with a reduced risk of distal colon cancer. The observed risk pattern was consistent with a threshold effect, suggesting that calcium intake beyond moderate levels may not be associated with a further risk reduction. Future investigations on this association should concentrate on specific cancer subsites and on the dose-response relationship.     

Glycemic index, glycemic load, and carbohydrate intake in relation to risk of distal colorectal adenoma in women.

Case-control studies and a cohort study have shown inconsistent associations between a high glycemic index or a high glycemic load and risk of colorectal cancer. These dietary variables have not been examined in relation to risk of colorectal adenoma. We thus examined the associations between dietary glycemic index, glycemic load, and carbohydrate intake with risk of adenoma of the distal colon or rectum among 34,428 US women who were initially free of cancer or polyps, who completed a semi-quantitative food-frequency questionnaire in 1980, and who underwent endoscopy from 1980 through 1998. 1,715 adenoma cases (704 large adenomas, 894 small adenomas, 1,277 distal colon adenomas, and 504 rectal adenomas) were documented during 18 years of follow-up. Dietary glycemic index, glycemic load, and carbohydrate intake were not related to risk of total colorectal adenoma after adjustment for age and established risk factors [relative risk (RR) for extreme quintiles of glycemic index = 1.11, 95% confidence interval (CI) 0.94-1.32, P for trend = 0.66; RR for glycemic load = 0.92, 95% CI 0.76-1.11, P for trend = 0.63; RR for carbohydrate intake = 0.90, 95% CI 0.73-1.11, P for trend = 0.64]. In addition, no significant associations were found for large or small adenoma, distal colon or rectal adenoma, or across strata of body mass index. Our findings do not support the hypothesis that a high glycemic index diet, a high glycemic load diet, or high carbohydrate intake overall are associated with risk of colorectal adenoma.     

Dietary patterns and subsequent colorectal cancer risk by subsite: a prospective cohort study

In order to investigate the associations between dietary patterns and the risk of colorectal cancer by subsite in Japan, the baseline data from a population-based cohort study of 20,300 men and 21,812 women were analyzed. We conducted factor analysis and identified 3 major dietary patterns, "healthy," "traditional" and "Western," and calculated the factor scores of each pattern for individuals. During 10 years of follow-up, 370 colorectal cancer cases were identified. We found a positive association between the traditional pattern and colon cancer risk in women [rate ratio for highest quartile (RR) = 2.06; 95% CI = 1.10-3.84; p for trend = 0.11], but not in men. This positive association was slightly stronger for proximal colon cancer (RR = 2.07; 95% CI = 0.84-5.12) than for distal colon cancer (RR = 1.84; 95% CI = 0.75-4.50). After multivariate adjustment, the Western dietary pattern was also positively associated with colon cancer risk in females (RR = 2.21; 95% CI = 1.10-4.45), with the strongest associations being observed for females with distal colon cancer (RR = 3.48; 95% CI = 1.25-9.65). We did not observe any significant association between the healthy dietary pattern and colon cancer risk. For rectal cancer, no significant associations were found for the 3 dietary patterns. In conclusion, we found that the traditional and the Western dietary patterns were positively associated with colon cancer risk in females.     

Relationship of diet to risk of colorectal adenoma in men.

BACKGROUND: Rates of colorectal cancer in various countries are strongly correlated with per-capita consumption of red meat and animal fat and inversely associated with fiber consumption. There have been few studies, however, of dietary risk factors for colorectal adenomas, which are precursors of cancer. PURPOSE: Our purpose was to determine prospectively the relationship between dietary factors and risk of colorectal adenomas. METHODS: Using data from the Health Professionals Follow-up Study, we documented 170 cases of adenomas of the left colon or rectum in 7284 male health professionals who completed a food-frequency questionnaire in 1986 and who had a colonoscopy or sigmoidoscopy between 1986 and 1988. Relative risk (RR) of adenoma was determined according to quintiles of nutrient intakes. RESULTS: After adjustment for total energy intake, saturated fat was positively associated with risk of colorectal adenoma (P for trend = .006); RR for the highest versus the lowest quintile of intake was 2.0 (95% confidence interval [CI] = 1.2-3.2). Dietary fiber was inversely associated with risk of adenoma (P for trend less than .0001); RR for men in the highest versus the lowest quintile was 0.36 (95% CI = 0.22-0.60). All sources of fiber (vegetables, fruits, and grains) were associated with decreased risk of adenoma. For subjects on a high-saturated fat, low-fiber diet, the RR was 3.7 (95% CI = 1.5-8.8) compared with those on a low-saturated fat, high-fiber diet. The ratio of the intake of red meat to the intake of chicken and fish was positively associated with risk of adenoma (P for trend = .02). CONCLUSIONS: These prospective data provide evidence for the hypothesis that a diet high in saturated fat and low in fiber increases the risk of colorectal adenoma. They also support existing recommendations to substitute chicken and fish for red meat in the diet and to increase intake of vegetables, fruits, and grains to reduce risk of colorectal cancer.     

Mismatch repair polymorphisms and the risk of colorectal cancer

Rare germline variants in mismatch repair genes have been linked to hereditary nonpolyposis colorectal cancer; however, it is unknown whether common polymorphisms in these genes alter the risk of colorectal cancer. To examine the association between common variants in mismatch repair genes and colorectal cancer, we conducted a case-cohort study within the CLUE II cohort. Four single nucleotide polymorphisms in 3 mismatch repair genes (MSH3 R940Q, MSH3 T1036A, MSH6 G39E and MLH1 I219V) were genotyped in 237 colorectal cancer cases and a subcohort of 2,189 participants. Incidence rate ratios (RRs) and 95% confidence intervals (95% CIs) for each polymorphism were estimated. The MSH3 1036A variant was found to be associated with an increased risk of colorectal cancer (RR=1.28, 95% CI: 0.94-1.74 and RR=1.65, 95% CI: 1.01-2.70 for the AT and TT genotypes, respectively, with p(trend)=0.02), particularly proximal colon cancer. Although the MSH3 940Q variant was only weakly associated with colorectal cancer overall (p(trend)=0.07), it was associated with a significant increased risk of proximal colon cancer (RR=1.69, 95% CI: 1.10-2.61 and RR=2.68, 95% CI: 0.96-7.47 for the RQ and QQ genotypes, respectively with p(trend)=0.005). Processed meat intake appeared to modify the association between the MSH3 polymorphisms and colorectal cancer (p(interaction) < 0.10 for both). No association was observed with the MSH6 and MLH1 polymorphisms overall. This study suggests that common polymorphisms in the mismatch repair gene, MSH3, may increase the risk of colorectal cancer, especially proximal colon cancer.     

Parity and other reproductive factors and risk of adenomatous polyps of the distal colorectum (United States)

Evidence for an effect of reproductive factors on colorectal carcinogenesis is inconsistent and little is known about their role in development of precursor adenomatous polyps. We evaluated the relation between reproductive factors and distal colorectal adenomas (n = 982) during14 years of follow up of 26,983 participants in the Nurses' Health Study(United States). The women were free of diagnosed cancer or polyps in 1980,underwent endoscopy 1980-94, and had reported on their parity, oral contraceptive (OC) use, and ages at menarche, first term-pregnancy, and menopause. We calculated relative risks (RR) and 95 percent confidence intervals (CI) using multiple logistic regression. Women with higher parity had an increased risk of adenomas of the distal colorectum (P trend = 0.004;6+ cf 0 parity: RR = 1.3, CI = 0.9-1.8) or distal colon (P trend = 0.002, RR= 1.7, CI = 1.2-2.6). This association was significantly stronger among women with a family history of colorectal cancer ( P interaction = 0.03); comparing6+ term-pregnancies with nulliparity, among those with a family history, the RR for distal colon adenoma was 3.2 (CI = 1.4-7.2), while among those without a family history, the RR was 1.3 (CI = 0.8-2.2). We observed no association for distal colorectal adenoma and age at menarche, age at first term-pregnancy, ever use of OCs, or menopausal status. Further work is needed to clarify the relation of parity with colon adenoma risk. This revised version was published online in July 2006 with corrections to the Cover Date.     

Radiation risk of incident colorectal cancer by anatomical site among atomic bomb survivors: 1958–2009

Radiation effects on colorectal cancer rates, adjusted for smoking, alcohol intake and frequency of meat consumption and body mass index (BMI) by anatomical subsite (proximal colon, distal colon and rectum) were examined in a cohort of 105,444 atomic bomb survivors. Poisson regression methods were used to describe radiation-associated excess relative risks (ERR) and excess absolute rates (EAR) for the 1958–2009 period. There were 2,960 first primary colorectal cancers including 894 proximal, 871 distal and 1,046 rectal cancers. Smoking, alcohol intake and BMI were associated with subsite-specific cancer background rates. Significant linear dose–responses were found for total colon (sex-averaged ERR/Gy for 70 years old exposed at age 30 = 0.63, 95% confidence interval [CI]: 0.34; 0.98), proximal [ERR = 0.80, 95% CI: 0.32; 1.44] and distal colon cancers [ERR = 0.50, 95% CI: 0.04; 0.97], but not for rectal cancer [ERR = 0.023, 95% CI: −0.081; 0.13]. The ERRs for proximal and distal colon cancers were not significantly different (p = 0.41). The ERR decreased with attained age for total colon, but not for proximal colon cancer, and with calendar year for distal colon cancer. The ERRs and EARs did not vary by age at exposure, except for decreasing trend in EAR for proximal colon cancer. In conclusion, ionizing radiation is associated with increased risk of proximal and distal colon cancers. The ERR for proximal cancer persists over time, but that for distal colon cancer decreases. There continues to be no indication of radiation effects on rectal cancer incidence in this population.     

Meat subtypes and their association with colorectal cancer: Systematic review and meta‐analysis

Associations between specific red meat subtypes and risk of colorectal cancer (CRC) have been investigated in a number of epidemiological studies. However, no publication to date has summarised the overall epidemiological evidence. We conducted a systematic review and meta‐analysis of prospective studies (cohort, nested case‐control or case‐cohort studies), which reported relative risk (RR) estimates and 95% confidence intervals (CI) for the association between intake of meat subtypes with colorectal, colon or rectal cancer or colorectal adenoma risk. PubMed and ISI Web of Science were searched up until August 1, 2014. Nineteen studies examined meat subtypes (5 beef, 5 pork, 2 lamb, 1 veal and 19 poultry) and associations with colorectal, colon or rectal cancer risk and 4 studies examined associations with adenoma risk (1 beef and 4 poultry). Comparing highest versus lowest intake, beef consumption was associated with an increased risk of CRC (RR = 1.11, 95% CI = 1.01 to 1.22) and colon cancer (RR = 1.24, 95% CI = 1.07 to 1.44), but no association was found with rectal cancer (RR = 0.95, 95% CI = 0.78 to 1.16). Higher consumption of lamb was also associated with increased risk of CRC (RR = 1.24, 95% CI = 1.08 to 1.44). No association was observed for pork (RR = 1.07, 95% CI = 0.90 to 1.27), but some between study heterogeneity was observed. No association was observed for poultry consumption and risk of colorectal adenomas or cancer. This meta‐analysis suggests that red meat subtypes differ in their association with CRC and its sub sites. Further analysis of data from prospective cohort studies is warranted, especially regarding the role of pork.     

Screening endoscopy and risk of colorectal cancer in United States men

Objectives: The purpose of this study was to describe the effect of screening endoscopy (sigmoidoscopy or colonoscopy) on colorectal cancer incidence and mortality. Methods: We used data from a prospective cohort study of 24,744 men aged 40 to 75 years in 1986, free from cancer and colon polyps, followed until 1994. The outcomes are diagnosis of colorectal cancer and death from colorectal cancer. Results: Screening endoscopy in 1986-87 was associated with a lower risk of all colorectal cancer (multivariate relative risk [RR]=0.58, 95 percent confidence interval [CI]=0.36-0.96); cancer in the distal colon or rectum (multivariate RR=0.40, CI=0.19-0.84); Dukes stage A&B (multivariate RR=0.66, CI=0.35-1.25); and Dukes stage C&D (multivariate RR=0.50, CI=0.20-1.26) colorectal cancer; and death from colorectal cancer (multivariate RR=0.56, CI=0.20-1.60), after adjusting for age and a wide range of colon cancer risk factors. Screening endoscopy in 1988-87 appeared to provide strong protection against distal stage C&D cancers (age-adjusted RR=0.16, CI=0.02-1.23) but no protection against proximal stage C&D cancers (age-adjusted RR=0.96, CI=0.32-2.91). Conclusions: This study provides strong evidence for a protective effect of screening sigmoidoscopy on colorectal cancer incidence and mortality and supports recommendations for screening sigmoidoscopy as an approach to colon cancer prevention.     

Meat, meat cooking methods and preservation, and risk for colorectal adenoma

Cooking meat at high temperatures produces heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Processed meats contain N-nitroso compounds. Meat intake may increase cancer risk as HCAs, PAHs, and N-nitroso compounds are carcinogenic in animal models. We investigated meat, processed meat, HCAs, and the PAH benzo(a)pyrene and the risk of colorectal adenoma in 3,696 left-sided (descending and sigmoid colon and rectum) adenoma cases and 34,817 endoscopy-negative controls. Dietary intake was assessed using a 137-item food frequency questionnaire, with additional questions on meats and meat cooking practices. The questionnaire was linked to a previously developed database to determine exposure to HCAs and PAHs. Intake of red meat, with known doneness/cooking methods, was associated with an increased risk of adenoma in the descending and sigmoid colon [odds ratio (OR), 1.26; 95% confidence interval (95% CI), 1.05-1.50 comparing extreme quintiles of intake] but not rectal adenoma. Well-done red meat was associated with increased risk of colorectal adenoma (OR, 1.21; 95% CI, 1.06-1.37). Increased risks for adenoma of the descending colon and sigmoid colon were observed for the two HCAs: 2-amino-3,8-dimethylimidazo[4,5]quinoxaline and 2-amino-1-methyl-6-phenylimidazo[4,5]pyridine (OR, 1.18; 95% CI, 1.01-1.38 and OR, 1.17, 95% CI, 1.01-1.35, respectively) as well as benzo(a)pyrene (OR, 1.18; 95% CI, 1.02-1.35). Greater intake of bacon and sausage was associated with increased colorectal adenoma risk (OR, 1.14; 95% CI, 1.00-1.30); however, total intake of processed meat was not (OR, 1.04; 95% CI, 0.90-1.19). Our study of screening-detected colorectal adenomas shows that red meat and meat cooked at high temperatures are associated with an increased risk of colorectal adenoma.     

Dietary soy and isoflavone intake and risk of colorectal cancer in the Japan public health center-based prospective study

Several experimental studies have reported that the anticarcinogenic properties of dietary soy play an important role in preventing colorectal cancer. However, few epidemiologic studies have examined this association in general populations and their findings have been inconsistent. We investigated the association between dietary soy and isoflavone intake and incidence of colorectal cancer in a prospective cohort study of 83,063 Japanese men and women, ages 45 to 74 years. Dietary soy and isoflavone intake was measured through a validated food frequency questionnaire in 1995 and 1998. Throughout 2004, a total of 886 cases of colorectal cancer were newly identified (291 proximal colon, 286 distal colon, and 277 rectum). The hazard ratios and 95% confidence intervals (95% CIs) were estimated by fitting a Cox proportional hazards model. The intake of isoflavones, miso soup, and soy food was not associated with colorectal cancer in either men or women. By colorectal cancer subsite, the risk of proximal colon cancer in men decreased with increasing consumption of isoflavones, miso soup, and soy food. Compared with men in the lowest quartiles of isoflavones, miso soup, and soy food intake, the hazard ratios in the highest quartiles were 0.55 (95% CI, 0.33-0.92), 0.72 (95% CI, 0.43-1.21), and 0.51 (95% CI, 0.30-0.87), respectively. The results showed no association for distal colon and rectal cancer in men or for subsites of colorectal cancer in women. These findings suggest that the intake of isoflavones, miso soup, and soy food has no substantial effect on the risk of colorectal cancer in Japanese men and women.     

p53 Arg72Pro polymorphism and risk of colorectal adenoma and cancer

A single nucleotide polymorphism (SNP) at codon 72 of the p53 gene (Arg72Pro) alters the p53 protein structure and affects its activity. We investigated this SNP in relation to colorectal adenoma and cancer among men and women from case-control studies nested within the Nurses' Health Study, the Health Professionals Follow-up Study and the Physicians' Health Study. Among 856 colorectal adenoma cases and 1,184 controls, we observed a modest association with p53 Arg72Pro genotype (multivariate odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.04-1.50 for Arg/Pro and Pro/Pro vs. Arg/Arg). This association did not vary by colorectal site or by sex. Among 442 colorectal cancer cases and 904 controls, we observed no significant overall association between p53 Arg72Pro genotype and colorectal cancer (multivariate OR = 1.14, 95% CI = 0.90-1.45). However, when colorectal site and sex was accounted for, the Pro carrier genotypes compared to Arg/Arg were associated with an increased risk of proximal colon cancers in women (multivariate OR = 2.59, 95% CI = 1.49-4.52) though not with distal colon or rectal cancers, while among men the same genotypes were associated with an increased risk of distal colon cancers (multivariate OR = 2.09, 95% CI = 1.28-3.40) but not proximal colon or rectal cancers. Our results suggest that Arg72Pro may play a role in the early stages of colorectal neoplasia and possibly in progression to invasive disease, depending on site and sex.     

Nonsteroidal anti-inflammatory drugs and subsite-specific colorectal cancer incidence in the Iowa women's health study.

BACKGROUND: Previous epidemiologic studies have shown that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with decreased colorectal cancer risk. However, few studies have examined associations between NSAID use and subsite-specific colorectal cancer risks. Because tumors of the proximal and distal colon differ with respect to their genetic alterations, clinicopathologic features, and demographic distribution, further investigation of subsite-specific colorectal cancer risks may be rewarding. METHODS: Data about aspirin and non-aspirin-NSAID use were recorded by self-report in 1992 among the initially cancer-free cohort of postmenopausal women in the Iowa Women's Health Study (n = 27,160). In total, 637 women developed colorectal cancer during the 11 years of follow-up, including 365 proximal colon, 132 distal colon, and 120 rectal cancer cases (11 overlapping and 9 not specified). RESULTS: For colon cancer, the multivariable-adjusted hazard ratios (HR) for women reporting use of aspirin two to five times and six or more times weekly (compared with nonusers of aspirin) were 0.79 [95% confidence interval (95% CI), 0.59-1.04] and 0.76 (95% CI, 0.58-1.00), respectively. The corresponding HRs for non-aspirin NSAIDs were 0.63 (95% CI, 0.41-0.96) and 0.85 (95% CI, 0.63-1.15), respectively. For proximal colon cancer, the multivariable-adjusted HRs for women reporting use of aspirin or non-aspirin NSAIDs two or more times weekly (compared with nonusers of each) were 0.67 (95% CI, 0.51-0.87) and 0.71 (95% CI, 0.52-0.97), respectively. No statistically significant association was found between either distal colon or rectal cancer and aspirin or non-aspirin NSAID use. DISCUSSION: Our study is consistent with a limited number of prior reports that have observed stronger associations between NSAID use and proximal versus distal colorectal cancer.     

Cigarette and alcohol consumption and the risk of colorectal cancer in Shanghai, China.

The relation of cigarette smoking and alcohol drinking to colorectal cancer risk has been inconsistent in the epidemiological literature. In a population-based case-control study of colorectal cancer in Shanghai, China, where the incidence rates are rising sharply, we examined the association with tobacco and alcohol use. Cases were aged 30-74 years and newly diagnosed with cancers of the colon (N = 931) or rectum (N = 874) between 1990 and 1992. Controls (N = 1552) were randomly selected among Shanghai residents, frequency-matched to cases by gender and age. Information on lifetime consumption of tobacco and alcohol, as well as demographic and other risk factors, was obtained through in-person interviews. Associations with cigarette smoking and alcohol use were estimated by odds ratios (ORs) and 95% confidence intervals (CIs). Among women, the prevalence of smoking and alcohol drinking was low, and no significant association with colon or rectal cancer was observed. Although cigarette smoking among men was not related overall to colon or rectal cancer risk, there was a 50% excess risk of rectal cancer (OR 1.5, 95% CI 0.9-2.5) among those who smoked 55 or more pack-years. Among men, former alcohol drinkers had an increased risk of colon cancer (OR 2.3, 95% CI 1.4-3.7) but not rectal cancer, while current drinkers had a 30-50% excess risk of colon cancer only among those with long-term (30+ years) and heavy (>560 g ethanol/week) consumption. The excess risks were mainly associated with hard liquor consumption, with no material difference in risk between proximal and distal colon cancer. Although cigarette smoking and alcohol drinking in general were not risk factors for colorectal cancers in Shanghai, there were small excess risks for rectal cancer among heavy smokers and colon cancer among heavy drinkers.     

Whole grain consumption and risk of colorectal cancer: a population-based cohort of 60,000 women

We examined prospectively the association between whole grain consumption and colorectal cancer risk in the population-based Swedish Mammography Cohort. A total of 61,433 women completed a food-frequency questionnaire at baseline (1987-1990) and, through linkage with the Swedish Cancer Registry, 805 incident cases of colorectal cancer were identified during a mean follow-up of 14.8 years. High consumption of whole grains was associated with a lower risk of colon cancer, but not of rectal cancer. The multivariate rate ratio (RR) of colon cancer for the top category of whole grain consumption (> or = 4.5 servings day(-1)) compared with the bottom category (<1.5 servings day(-1)) was 0.67 (95% confidence interval (CI), 0.47-0.96; P-value for trend=0.06). The corresponding RR after excluding cases occurring within the first 2 years of follow-up was 0.65 (95% CI, 0.45-0.94; P-value for trend=0.04). Our findings suggest that high consumption of whole grains may decrease the risk of colon cancer in women.     

Diabetes mellitus and subsite-specific colorectal cancer risks in the Iowa Women's Health Study.

OBJECTIVE: Controversy remains regarding the association between type 2 diabetes mellitus (DM) and colorectal cancer (CRC) risk. To clarify and extend the existing data, we prospectively evaluated the association between self-reported type 2 DM (onset at >30 years of age) and incident CRC, overall and by anatomic subsite, among postmenopausal women in the Iowa Women's Health Study (n = 35,230).METHODS: After 14 years of follow-up, a total of 870 incident CRC cases were identified through annual linkage to the Iowa Cancer Registry. DM was analyzed as reported at baseline and as a time-dependent variable using information obtained during follow-up. CRC risks were estimated using Cox proportional hazards regression models.RESULTS: After adjusting for age, body mass index and other potential confounding variables, the relative risk (RR) for women with DM versus women without DM was modestly increased at 1.4 [95% confidence interval (95% CI), 1.1-1.8]. By anatomic subsite, the RR for proximal colon cancer was statistically significantly increased (RR, 1.9; 95% CI, 1.3-2.6), whereas the RRs for distal colon (RR, 1.1; 95% CI, 0.6-1.8) and rectal cancer (RR, 0.8; 95% CI, 0.4-1.6) were not statistically different from unity. Analyses that included DM ascertained at baseline and follow-up yielded similar results.CONCLUSION: In this large, prospective study of postmenopausal women, the association between DM and incident CRC was found to be subsite specific. If confirmed by others, this finding implies that CRC prevention strategies among type 2 DM patients should include examination of the proximal colon.