Effect of age factors on health-related quality of life in patients with lower rectal cancer after sphincter-saving surgery: A 1-year longitudinal study.

PURPOSE: To examine age-related factors influencing health-related quality of life (HR-QOL) among patients with lower rectal cancer during the 12-month period after sphincter-saving surgery (SSS). MATERIAL AND METHODS: In this 1-year longitudinal study, 137 patients (120 patients completed, and 82 aged ≥60 years) answered the European Organization for Research and Treatment of Cancer questionnaire (EORTC-C30/CR38) assessing their HR-QOL and related factors during the 12 months after SSS. RESULTS: No significant differences in HR-QOL were found before surgery. Only among those aged ≥60 years, global health status/QOL and cognitive functioning showed a significant decrease one month after surgery. At one month after SSS, the role functioning of groups <60 years old (which is negatively related to defecation problems, insomnia, and financial difficulties) was lower compared to those aged ≥60 years; and role functioning was significantly related to global health status/QOL. Six months after SSS, the global health status/QOL had recovered. In both groups, global health status/QOL was related to role and social functioning. Among participants aged <60 years, global health status/QOL was significantly related to emotional functioning, which is related to future perspective. Among participants aged ≥60 years only, global health status/QOL was significantly related to cognitive functioning; pain, financial difficulties, and defecation problems negatively influenced HR-QOL. Symptoms specific after SSS: defecation problems (in both group), micturition problems (only ≥60 years), and sexual problems (only<60 years) influenced HR-QOL. CONCLUSION: Health care providers should assess the influence of age-related factors during the early post-operative period after SSS to improve HR-QOL.

Anal Canal Duplication Associated with Presacral Cyst in an Adult.

Anal canal duplication (ACD) is a rare congenital malformation, usually detected early in life. We report a case of a 67-year-old female with symptomatic ACD associated with a presacral cyst. Physical examination revealed an accessory opening located in the midline, posterior to the true anus. Imaging examinations, including fistulography, endoanal ultrasonography, and magnetic resonance imaging, revealed a blind-ending fistulous tract without connecting with the rectum and a presacral cyst posterior to the rectum. Complete surgical excision of the tract with cyst was performed through a posterior sagittal approach. Histologic examination revealed squamous epithelium lining and smooth muscle bundles, thereby confirming ACD. The postoperative course was uneventful, and the patient was doing well; no recurrence was observed 4 years after surgery. ACD can present for the first time in infants, children, and adults. Imaging examinations are useful for the diagnosis and preoperative assessment of ACD. Therefore, ACD should be considered in the differential diagnosis, even in adults, when a posterior perineal orifice is encountered, particularly in female patients. Once ACD is suspected, intense imaging inspection is recommended to visualize the ACD and associated anomalies, and surgical removal is warranted to prevent inflammatory complications or malignant changes.

Effects of chemotherapy on the health-related quality of life of Japanese lower rectal cancer patients after sphincter-saving surgery.

We examined the effects of adjuvant chemotherapy on the health-related quality of life (HRQOL) of lower rectal cancer patients receiving sphincter-saving surgery (SSS). In all, 109 patients completed a questionnaire before surgery and 1, 6, and 12 months afterwards. In the chemotherapy group, physical and social functioning scores were significantly lower 12 months after surgery compared with the nonchemotherapy group. These effects of adjuvant chemotherapy suggest that a different clinical approach might more effectively improve physical and social functioning in lower-rectal cancer patients undergoing chemotherapy. Healthcare providers should be alert for adverse events in patients with lower-rectal cancer and promptly address such conditions.

Endoanal Ultrasonography of Mucinous Adenocarcinoma Arising from Chronic Fistula-in-ano: Three Case Reports.

Mucinous adenocarcinoma arising in chronic fistula-in-ano is rare, and diagnosing it at an early stage is difficult. The role of endoanal ultrasonography in diagnosing the condition has not been discussed in the study. Herein, we report three cases of mucinous adenocarcinoma arising from anal fistulas in which endosonography played an important role in diagnosing malignant change. Three male patients with a 5- to 20-year history of anal fistula were referred to our hospital due to perianal induration, progressive anal pain, or mucopurulent secretion. In all three patients, endosonography revealed a multiloculated complex echoic mass with isoechoic solid components communicating with a trans-sphincteric fistula and sonography-guided biopsy under anesthesia revealed mucinous adenocarcinoma. All patients underwent abdominoperineal resection with lymph node dissection. One patient with a local recurrence died 3 years after surgery and two have remained disease-free for >6 years. These observations suggest that endosonography may be a reliable technique for the diagnosis of mucinous adenocarcinoma arising from chronic fistula-in-ano. Sonography-guided biopsy is useful for the definitive diagnosis of malignancy. Therefore, periodic endosonography assessment should be recommended for patients with persistent anal fistula, especially those with progressive clinical symptoms. Once malignancy is suspected, aggressive sonography-guided biopsy under anesthesia should be performed, which may enable an early diagnosis, curative treatment, and favorable long-term results.

A longitudinal study of gender differences in quality of life among Japanese patients with lower rectal cancer treated with sphincter-saving surgery: a 1-year follow-up.

BACKGROUND: Up to 80% of patients with rectal cancer undergo sphincter-saving surgery, and almost 90% of them experience subsequent physical changes. The number of studies on gender differences in response to this surgery has increased, and the connection between gender and symptoms and patient outcomes has generated increasing interest. Nevertheless, little is known about the gender differences in quality of life and cancer-related symptoms. We examined gender differences and quality of life changes over a 1-year period among patients with lower rectal cancer who were treated with sphincter-saving surgery. METHODS: Patients (men = 42; women = 33) completed a self-administered questionnaire on their quality of life and related factors before surgery and 1, 6, and 12 months afterwards. The questionnaire was developed by the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30/CR-38). RESULTS: Scores on physical, role, and social functioning and global health status/quality of life decreased 1 month after surgery, improved after 6 months, and returned to baseline within 12 months, with the exception of social functioning in men. Factors related to quality of life changed after surgery and differed between men and women. Women's global health status/quality of life was affected by fatigue, weight loss, defecation problems, and future perspective, while that of men was affected by fatigue, weight loss, future perspective, and role functioning, which was affected by pain, defecation problems, and financial difficulties. CONCLUSIONS: Gender differences should be considered when predicting the quality of life of cancer patients undergoing surgery. Identifying gender differences will help health care providers anticipate the unique needs of patients undergoing surgery for rectal cancer.

Side-to-side isoperistaltic strictureplasty for chronic ischemic enteritis: report of a case.

Chronic ischemic enteritis can cause intestinal strictures, but extensive resection of the small intestine may leave patients with short bowel syndrome. Thus, the importance of preserving diseased small bowel is now recognized. We report a case of successful side-to-side isoperistaltic strictureplasty (SSIS), performed to prevent short bowel syndrome, in a patient with ischemic enteritis caused by strangulated intestinal obstruction. SSIS is useful for preserving the intestinal absorptive function in patients with a long narrowed bowel loop caused by ischemic change. To our knowledge, this is the first report of the successful treatment of a long stricture resulting from ischemic enteritis, achieved by performing SSIS.

Dual blockade of phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways overcomes paclitaxel-resistance in colorectal cancer.

Paclitaxel, one of key drugs to treat a wide range of malignancies, exhibits relative low sensitivity for colorectal cancer. The present study was to examine whether and how phosphatidylinositol 3'-kinase (PI3K) signals affect the sensitivity of colorectal cancer to paclitaxel. Four colorectal cancer cell lines were exposed to paclitaxel in the presence of PI3K signal inhibitors, such as LY294002, siRNA for Akt, or rapamycin, with or without MAPK inhibitor, PD98059. Cell viability and apoptosis were determined by MTT assay, cell cycle analysis in flow cytometer and Hoechst nuclear staining. To analyze the PI3K activity, the expression in phosphorylated Akt and downstream effectors of p70S6 kinase (S6K) were evaluated by Western blot analysis. Paclitaxel alone (5-10 nM) did not induce the apoptosis in all four cell lines. Although LY294002 alone did not affect the cell viability, it suppressed the Akt and S6K activities and induced the sub-G1 arrest/apoptosis when paclitaxel was co-administered, as well as the Akt siRNA and rapamycin did. Simultaneous blockade of PI3K and MAPK pathways more suppressed the S6K activity and further increased the apoptosis. In conclusion, PI3K is involved in low susceptibility of colorectal cancer to paclitaxel and dual PI3K/MAPK targeting agents may evolve a new paclitaxel-based chemotherapy for colorectal cancer.

Soy food and isoflavone intake and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.

OBJECTIVE: It has been suggested that soy food and isoflavone intake may be protective against the risk of colorectal cancer. However, epidemiologic evidence remains sparse and inconsistent. We addressed this issue in the Fukuoka Colorectal Cancer Study. MATERIAL AND METHODS: The study subjects were the 816 incident cases of histologically confirmed colorectal cancer and 815 community controls. Intakes of soy foods and isoflavones were assessed by in-person interview using a computer-assisted dietary method. Logistic regression analysis was applied to estimate odds ratio (OR) and 95% confidence interval (CI) of colorectal cancer with adjustment for dietary intakes of calcium and n-3 polyunsaturated fatty acids as well as for body mass index, physical activity, alcohol use, and other lifestyle factors. RESULTS: Energy-adjusted intakes of soy foods (dry weight) and isoflavones were inversely associated with colorectal cancer risk in men and postmenopausal women, but not in premenopausal women. The multivariate-adjusted OR for the highest versus lowest quintile was 0.65 (95% CI 0.41-1.03, p for trend = 0.03) for soy foods and 0.68 (95% CI 0.42-1.10, p for trend = 0.051) for isoflavones in men. The corresponding values for postmenopausal women were 0.60 (95% CI 0.29-1.25, p for trend = 0.053) and 0.68 (95% CI 0.33-1.40, p for trend = 0.049). The site-specific analysis showed inverse associations of soy foods (p for trend = 0.007) and isoflavones (p for trend = 0.02) with rectal cancer in men. CONCLUSION: The findings add to epidemiologic evidence for protective effects of soy foods and isoflavones in colorectal carcinogenesis.

TP53 R72P and MDM2 SNP309 polymorphisms and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.

OBJECTIVE: Tumor protein p53 gene and its negative regulator, murine double minute 2 homolog are important components for cell-cycle arrest and apoptosis. An arginine-to-proline substitution at codon 72 in the p53 gene is reported to decrease apoptotic potential, while a thymine-to-guanine polymorphism at nucleotide 309, named SNP309, of murine double minute 2 gene increases transcription of the gene. These two polymorphisms therefore may be of importance in colorectal carcinogenesis. The relation of these polymorphisms to colorectal cancer risk was addressed in the Fukuoka Colorectal Cancer Study. METHODS: We genotyped the two polymorphisms in 685 incident cases of colorectal cancer and 778 community controls by the polymerase chain reaction-restriction fragment length polymorphism method. Statistical adjustment was made for sex and age. RESULTS: The proline allele of p53 gene and the guanine allele of SNP309 were each associated with a small, statistically non-significant increase in the odds ratio of colorectal cancer; the adjusted odds ratio (95% confidence interval) for arginine/proline and proline/proline genotypes combined versus arginine/arginine genotype of p53 gene was 1.23 (0.99-1.52) and that for thymine/guanine and guanine/guanine genotypes combined versus thymine/thymine genotype of SNP309 was 1.27 (0.98-1.63). Individuals harboring the proline allele of p53 gene and the guanine allele of SNP309 showed an odds ratio of 1.67 (95% confidence interval, 1.11-2.51). CONCLUSIONS: Codon 72 polymorphism of p53 and SNP309 in combination may confer an increased risk of colorectal cancer.

Dietary patterns and colorectal cancer in a Japanese population: the Fukuoka Colorectal Cancer Study.

Few studies have addressed the relation between dietary patterns and colorectal cancer in Japan. We investigated dietary patterns in relation to colorectal cancer risk in a community-based case-control study. The association with dietary patterns was also examined for different sites of colorectal cancer. Data were derived from the Fukuoka Colorectal Cancer Study, including 800 cases and 775 controls interviewed from September 2000 to December 2003. The cases were admitted to one of the participating hospitals for the first surgical treatment during this period. We identified dietary patterns using principal component analysis of intakes of twenty-nine items of food groups and specific foods. Quartile categories of each dietary pattern were used, and non-dietary lifestyle factors and total energy intake were adjusted for in the analysis. We identified three dietary patterns: prudent, high-fat and light-meal patterns. The prudent dietary pattern characterised by high intakes of vegetables, fruits, seafoods and soya foods showed a nearly significant protective association with the overall risk of colorectal cancer (trend P = 0.054), and it was statistically significantly related to a decreased risk of distal colon cancer (trend P = 0.002), but not to that of either proximal colon or rectal cancer. The high-fat and light-meal dietary patterns were not materially related to the overall or site-specific risk of colorectal cancer. In summary, a prudent dietary pattern was associated with a decreased risk of colorectal cancer, especially with that of distal colon cancer, in a fairly large case-control study in Japan.

Cigarette smoking, genetic polymorphisms and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.

BACKGROUND: It is uncertain whether smoking is related to colorectal cancer risk. Cytochrome P-450 CYP1A1, glutathione-S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are important enzymes in the metabolism of tobacco carcinogens, and functional genetic polymorphisms are known for these enzymes. We investigated the relation of cigarette smoking and related genetic polymorphisms to colorectal cancer risk, with special reference to the interaction between smoking and genetic polymorphism. METHODS: We used data from the Fukuoka Colorectal Cancer Study, a population-based case-control study, including 685 cases and 778 controls who gave informed consent to genetic analysis. Interview was conducted to assess lifestyle factors, and DNA was extracted from buffy coat. RESULTS: In comparison with lifelong nonsmokers, the odds ratios (OR) of colorectal cancer for <400, 400-799 and > or = 800 cigarette-years were 0.65 (95% confidence interval [CI], 0.45-0.89), 1.16 (0.83-1.62) and 1.14 (0.73-1.77), respectively. A decreased risk associated with light smoking was observed only for colon cancer, and rectal cancer showed an increased risk among those with > or = 400 cigarette-years (OR 1.60, 95% CI 1.04-2.45). None of the polymorphisms under study was singly associated with colorectal cancer risk. Of the gene-gene interactions studied, the composite genotype of CYP1A1*2A or CYP1A1*2C and GSTT1 polymorphisms was associated with a decreased risk of colorectal cancer, showing a nearly statistically significant (Pinteraction = 0.06) or significant interaction (Pinteraction = 0.02). The composite genotypes of these two polymorphisms, however, showed no measurable interaction with cigarette smoking in relation to colorectal cancer risk. CONCLUSIONS: Cigarette smoking may be associated with increased risk of rectal cancer, but not of colon cancer. The observed interactions between CYP1A1 and GSTT1 polymorphisms warrant further confirmation.

Dietary fiber, source foods and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.

OBJECTIVE: Despite much evidence from laboratory work, epidemiological evidence remains elusive regarding the role of dietary fiber in colorectal carcinogenesis. We investigated associations of dietary fiber and source foods with colorectal cancer risk in the Fukuoka Colorectal Cancer Study, a community-based case-control study. MATERIAL AND METHODS: The study subjects were 816 incident cases of colorectal cancer and 815 community controls. Nutrient and food intakes were estimated on the basis of a computer-assisted interview regarding 148 dietary items. Odds ratios of colorectal cancer according to quintile categories of energy-adjusted intakes of dietary fiber and food groups were obtained with adjustment for non-dietary factors and dietary intakes of calcium and n-3 fatty acids. RESULTS: Total, soluble and insoluble dietary fibers were not measurably associated with overall risk or subsite-specific risk of colorectal cancer. By contrast, rice consumption was associated with a decreased risk of colorectal cancer (trend p = 0.03), particularly of distal colon and rectal cancer (trend p = 0.02), and high intake of non-rice cereals tended to be related to an increased risk of colon cancer (trend p = 0.07). There was no association between vegetable consumption and colorectal cancer, whereas individuals with the lowest intake of fruits tended to have an increased risk of colorectal cancer. CONCLUSIONS: The present study did not corroborate a protective association between dietary fiber and colorectal cancer, but suggested a decreased risk of distal colorectal cancer associated with rice consumption.

Enhancement of paclitaxel-induced apoptosis by inhibition of mitogen-activated protein kinase pathway in colon cancer cells.

Resistance to chemotherapy represents a major obstacle to improving the survival of patients with colorectal cancer. In this study, the inhibition of the mitogen-activated protein kinase (MAPK) pathway was demonstrated to markedly enhance the apoptosis of colon cancer cells induced by paclitaxel, one of the key chemotherapeutic drugs widely used to treat various types of cancer. The treatment of the colon cancer cell lines SW480 and DLD-1 with paclitaxel resulted in increased activation of the MAPK pathway, which was blocked by PD98059, a MEK inhibitor. In both cell lines, MAPK inhibition by PD98059 led to a dramatic enhancement of the paclitaxel-induced apoptosis, as determined by cell cycle analysis and Hoechst 33342 staining, although the inhibitor alone did not affect apoptosis. This effect was restricted to paclitaxel since PD98059 did not alter the sensitivity to other drugs, including 5-fluorouracil (5-FU) and camptothecin (CPT). Importantly, selective blockage of the MAPK pathway by small interfering RNA (siRNA) also increased the apoptotic cell death induced by paclitaxel. These findings highlight the importance of the MAPK pathway in paclitaxel-induced apoptosis and suggest that a combined treatment with paclitaxel and MEK inhibitors could be an attractive therapeutic strategy against colon cancer.

Genetic polymorphisms of CYP2E1 and risk of colorectal cancer: the Fukuoka Colorectal Cancer Study.

Cytochrome P450 2E1 (CYP2E1) is involved in the metabolic activation of a wide variety of potential carcinogens, and functional polymorphisms in the CYP2E1 gene have been investigated in relation to colorectal cancer. We examined the relation of the CYP2E1 RsaI and 96-bp insertion polymorphisms to colorectal cancer risk and the interaction between these polymorphisms and some lifestyle risk factors. Subjects were 685 incident cases of colorectal cancer and 778 community controls. Statistical adjustment was made for alcohol use, body mass index, physical activity, and other factors. The RsaI c2 allele was associated with a decreased risk of rectal cancer [adjusted odds ratio for at least one c2 allele, 0.71; 95% confidence interval (95% CI), 0.53-0.95], and an increased risk of rectal cancer was observed among individuals having one or two 96-bp insertion alleles (adjusted odds ratio, 1.40; 95% CI, 1.06-1.85). Individuals with two 96-bp insertion alleles showed a 2.28-fold increase in colon cancer risk (95% CI, 1.29-4.01). The two polymorphisms were in almost complete linkage disequilibrium (D' = 0.94). A positive association between alcohol intake and colorectal cancer was observed only in individuals without RsaI c2 allele (P(trend) = 0.03) or in those without 96-bp insertion allele (P(trend) = 0.009). Colon cancer risk was increased in relation to red meat intake only in individuals having one or two 96-bp insertion alleles (P(interaction) = 0.03). The present study suggests that variation in activity and inducibility of CYP2E1, in relation to alcohol or red meat intake, contributes to the development of colorectal cancer.

Calcium, dairy foods, vitamin D, and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.

Epidemiologic evidence supporting a protective role of calcium and vitamin D in colorectal carcinogenesis has been accumulating in Western populations, but it is limited in Asian populations, whose intake of calcium is relatively low. We investigated the association of intakes of these nutrients with colorectal cancer risk in Japanese. Study subjects were participants of a large-scale case-control study in Fukuoka, Japan. Diet was assessed through interview regarding 148 dietary items by showing typical foods or dishes on the display of a personal computer. In a multivariate analysis adjusting for potential confounding variables, calcium intake was significantly, inversely associated with colorectal cancer risk (P for trend=0.01); the odds ratio for the highest versus lowest quintile of calcium intake was 0.64 (95% confidence interval, 0.45-0.93). Higher levels of dietary vitamin D were significantly associated with decreased risk of colorectal cancer among those who had fewer chances of sunlight exposure at work or in leisure (P for trend=0.02). A decreased risk of colorectal cancer associated with high calcium intake was observed among those who had higher levels of vitamin D intake or among those who had a greater chance of daily sunlight exposure, but not among those with medium or lower intake of vitamin D or among those with potentially decreased sunlight exposure. These results add to support for a joint action of calcium and vitamin D in the prevention of colorectal carcinogenesis.

Personality and colorectal cancer: the Fukuoka colorectal cancer study.

OBJECTIVE: Although personality factors, especially emotional suppression and loss-hopelessness, have been linked to the occurrence and progression of cancer, little is reported specifically on colorectal cancer. It has also been claimed that a 'hysterical' personality characterized by exaggerated emotional expressions, egocentricity and ambivalent connection may be protective from cancer. This community-based case-control study examined whether personality factors relevant to emotional suppression or loss-hopelessness are associated with an increased risk of colorectal cancer, and whether factors related to the hysterical personality are associated with a decreased risk. METHODS: The stress inventory (SI), a self-administered questionnaire to assess the possible disease-prone and other relevant personalities in Japanese, was completed by 497 patients with newly diagnosed colorectal cancer and 809 controls randomly selected in the Fukuoka area of Japan. RESULTS: After controlling for age, sex and residence using a logistic regression model, none of the SI scales relevant to emotional suppression ('unfulfilled needs for acceptance', 'altruism', 'rationalizing conflicts/frustrations') or loss-hopelessness ('low sense of control', 'object-dependence/loss', 'object-dependence/happiness') was related to colorectal cancer. On the other hand, two scales representing elements of the hysterical personality, 'object-dependence/ambivalence' and 'egoism' were protectively associated with risk. Additional adjustment for body-mass index and lifestyle factors did not materially change these associations. CONCLUSIONS: Although personalities relevant to the emotional suppression or loss-hopelessness may not be a risk factor for colorectal cancer in the Japanese population, ambivalent connection and egocentricity may be protective.

Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population.

The MUTYH gene encodes a DNA glycosylase that can initiate the base excision repair pathway and prevent G:C > T:A transversion by excising adenine mispaired with 8-hydroxyguanine. Biallelic germline mutations of MUTYH have been shown to predict familial and sporadic multiple colorectal adenomas and carcinomas, however, whether there is an association between single nucleotide polymorphisms (SNPs) of MUTYH and sporadic colorectal cancer (CRC) risk has remained unclear. In this study we investigated four MUTYH SNPs, IVS1+11C > T, IVS6+35G > A, IVS10-2A > G, and 972G > C (Gln324His), for an association with increased CRC risk in a population-based series of 685 CRC patients and 778 control subjects from Kyushu, Japan. A statistically significant association was demonstrated between IVS1+11T and increased CRC risk (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.012-2.030; P = 0.042) and one of the five haplotypes based on the four SNPs, the IVS1+11T - IVS6+35G - IVS10-2A - 972C (TGAC) haplotype containing IVS1+11T, was demonstrated to be associated with increased CRC risk (OR, 1.43; 95% CI, 1.005-2.029; P = 0.046). Subsite-specific analysis showed that the TGAC haplotype was statistically significantly (P = 0.013) associated with an increased risk of distal colon, but not proximal colon or rectal cancer. Furthermore, IVS1+11C > T was found to be in complete linkage disequilibrium with -280G > A and 1389G > C (Thr463Thr). The results indicated that Japanese individuals with - 280A/IVS1+11T/1389C genotypes or the TGAC haplotype are susceptible to CRC.

Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell cycle-related protein expression.

OBJECTIVE: To investigate the effects of medroxyprogesterone acetate on colon cancer cells in vitro. DESIGN: HT29 and HCT116 human colon cancer cell lines were used in this study. Cell growth and WST-1 assays were performed to investigate the antiproliferative effect of medroxyprogesterone acetate. Cell cycle analysis was performed to investigate the effects of medroxyprogesterone acetate on cell cycle distribution. Western blot, immunoprecipitation, and a cyclin-dependent kinase assay were performed to investigate changes in the levels of cell cycle proteins. RESULTS: Medroxyprogesterone acetate inhibited proliferation of the cancer cells by inducing accumulation in the G0/G1 fraction. Medroxyprogesterone acetate decreased expression of cyclin E, increased expression of p21(WAF1/CIP1), and enhanced interaction of p21(WAF1/CIP1) with cyclin-dependent kinase 2, eventually inhibiting its activity. CONCLUSIONS: Medroxyprogesterone acetate exerts its antiproliferative effect by modulating cell cycle-related protein expression and cyclin-dependent kinase 2 activity. These results should help to elucidate the protective effect of medroxyprogesterone acetate on colon cancer risk.

Colorectal polypectomy and risk of colorectal cancer by subsite: the Fukuoka Colorectal Cancer study.

BACKGROUND: Colorectal adenomas are well-established precursor lesions for colorectal cancer and removal of polyps is deemed to reduce the risk of colorectal cancer. However, benefit of colorectal polypectomy in routine practice is still uncertain. We therefore investigated subsite-specific risks of colorectal cancer in relation to history of colorectal polypectomy in a case-control study. METHODS: Both case patients and control subjects were residents aged 20-74 years in Fukuoka City and three adjacent areas. The case group comprised 840 patients undergoing surgery for a first diagnosis of colorectal cancer, while the control subjects were 833 residents who were selected in the community by two-stage random sampling. Past history of selected diseases, surgery and lifestyle factors were ascertained by in-person interview. Statistical adjustment was made for sex, 5-year age class, residence, smoking, alcohol drinking, physical activity, body mass index and parental history of colorectal cancer. RESULTS: Overall, 74 case patients (9%) and 85 control subjects (10%) reported a prior history of colorectal polyps, and 50 cases (6%) and 64 controls (8%) had a history of colorectal polypectomy. The adjusted odds ratio associated with colorectal polypectomy was 0.71 (95% confidence interval [CI] 0.48-1.06) for the overall risk of colorectal cancer. The corresponding values for cancer of the proximal colon, distal colon, and rectum were 1.68 (95% CI 0.98-2.88), 0.71 (95% CI 0.41-1.26) and 0.24 (95% CI 0.11-0.52), respectively. CONCLUSIONS: The findings indicate that colorectal polypectomy in current practice confers a decreased risk of rectal cancer and possibly of distal colon cancer.

Hypermethylation of p14 (ARF) may be predictive of colitic cancer in patients with ulcerative colitis.

PURPOSE: The microsatellite instability and CpG island hypermethylation of p14 ( ARF ) and p16 ( INK4a ) are related to the pathogenesis of neoplasia in ulcerative colitis. This study was designed to assess the significance of those genetic or epigenetic alterations for cancer surveillance in ulcerative colitis. METHODS: During surveillance colonoscopy in 39 patients with ulcerative colitis, biopsy specimens were obtained from the cecum and the rectum as well as from any other areas suspected of being neoplasia by chromoscopy. Using DNA extracts, the methylation status of p14 ( ARF ) and p16 ( INK4a ) and the microsatellite status were determined. RESULTS: Microsatellite instability was positive in one of five dysplasias, but it was negative in the cecum and the rectum. The incidence of hypermethylation of p14 ( ARF ) was 0 percent in the cecum, 26 percent in the rectum, and 100 percent in dysplasia, whereas that of p16 ( INK4a ) was 10, 10, and 0 percent, respectively. Patients who were positive for the hypermethylation of p14 ( ARF )in the rectum had a longer duration of ulcerative colitis than those who were negative for such hypermethylation. Two of 10 patients who were positive for p14 ( ARF ) hypermethylation in the rectum and 1 of 29 patients who were negative for the hypermethylation had dysplasia. During the subsequent surveillance of 36 patients, dysplasia was detected in 2 of 8 patients with p14 ( ARF ) hypermethylation and in none of 28 patients without hypermethylation (P = 0.044). CONCLUSIONS: In patients with ulcerative colitis, hypermethylation of p14 ( ARF ) seems to be associated with an early stage of dysplasia. The hypermethylation may be one of candidates for potential biomarker to identify patients at a high risk of dysplasia.