Familial Colorectal Cancer Registry Research Articles

Abstract 4818: Type 2 diabetes mellitus and colorectal neoplasia risk in Puerto Rican Hispanics: A case-control study.

Abstract Introduction: Epidemiological studies have provided inconclusive evidence regarding the potential link between type 2 diabetes mellitus (DM) and colorectal cancer (CRC).The association between type 2 DM and colorectal neoplasia (colorectal cancer and/or adenomas) has not been well studied in Hispanics, an ethnic minority at high risk for type 2 DM.The specific aim of the study was to evaluate the association between type 2 DM and colorectal neoplasia (CRN) in Puerto Rican Hispanic adults enrolled in the studies Epidemiology of Loss of Imprinting in Colorectal Cancer, Familial Colorectal Cancer Registry and the Type 2 diabetes mellitus and colorectal neoplasia risk in Hispanics: A case-control study at the VA Caribbean Healthcare System. Methods: The case-control study included patients with incident CRN and controls with negative colonoscopy and without previous history of CRC or adenomas diagnosed from January 1, 2005 to December 31, 2009. Diagnosis of type 2 DM was established by previous medical diagnosis and/or anti-diabetic medications use. Unconditional logistic regression was employed to estimate the odds ratio (OR) between type 2 DM and CRN using STATA 10.0. Results: A total of 501 participants (mean age 60.3 ± 12.6 yrs., 57.9% males), prevalence of type 2 DM was 24.8%. 323 patients with CRN and 178 controls were evaluated. In the cases, the prevalence of colorectal adenomas was 25.7% (83/323) and the prevalence of colorectal cancer was 74.3% (240/323). Cases and controls did not differ by gender (p=0.19), median age (p=0.91), family history of CRC (p=0.76) and first degree of family history of DM (p=0.49). Cases had lower education (p<0.001) and reported lower use of NSAIDS (p=0.054) and physical activity (p=0.005) compared to the controls. There were no statistical significant associations between DM and CRN (OR=1.21; 95% CI: 0.79-1.87), DM and CRC (OR=1.20; 95% CI: 0.76-1.90) or DM and colorectal adenomas (OR=1.24; 95% CI: 0.68-2.27). Conclusions: We did not observe a statistical significant association between type 2 DM and CRN. Nonetheless, a tendency towards an increase risk of colorectal neoplasia was observed among type 2 DM patients. Possible explanation for our lack of association may be related to high prevalence of type 2 DM in cases and controls. Citation Format: Yaritza Diaz-Algorri, Dilka Gonzalez, Maria E. Lozada, Sofia Margarita Lopez-Diaz, Jessica Hernandez, Carmen Pedrosa, Doris Toro, Marcia R. Criuz-Correa. Type 2 diabetes mellitus and colorectal neoplasia risk in Puerto Rican Hispanics: A case-control study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4818. doi:10.1158/1538-7445.AM2013-4818

Clinical characterization and mutation spectrum in Hispanic families with adenomatous polyposis syndromes

Several genetically defined hereditary colorectal cancer (CRC) syndromes are associated with colonic polyposis including familial adenomatous polyposis (FAP) and MUTYH adenomatous polyposis (MAP). Limited data exists on the clinical characterization and genotypic spectrum of polyposis syndromes among Hispanics. To describe the phenotype and genotype of Puerto Rican Hispanic patients with FAP and MUTYH and compare with other ethnic and racial groups. Probands were identified from the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). Recruited individuals completed risk factors, medical, and family history questionnaires and underwent genetic testing for genotype analysis. Frequency analysis, Chi square, Fisher's exact and Wilcoxon rank-sum tests were used for statistical analysis methods. A total of 31 FAP (from 19 families) and 13 MAP (from 13 families) Hispanic patients recruited from the PURIFICAR were evaluated. Among the FAP cases, mean age at diagnosis was 27.6 (range 9-71 years); 67.7 % cases had more than 100 polyps and 41.9 % had upper gastrointestinal polyps. Among the 19 FAP families, there were 77 affected FAP individuals and 26 colorectal cancer cases. Genetic mutations were available for 42.2 % of FAP families; all mutations identified were unique. Surgeries were reported in 31 cases; 14 (45.2 %) prophylactic surgeries and 6 (19.4 %) therapeutic surgeries for management of CRC. Among MAP cases, mean age at diagnosis was 53 (range 34-76 years). Genetic analysis revealed homozygous biallelic mutations (G382D) in 53.8 %, compound heterozygous mutations (G382/Y165C) in 23 %, and non-G382/Y165C monoallelic mutations in 23 %. Familial cancer registries should be promoted as vehicles for detection, education and follow up of families at-risk of acquiring familial cancers. PURIFICAR is the first and only familial cancer registry in Puerto Rico providing these services to families affected with familial cancer syndromes promoting education, testing and surveillance of at-risk family members, and focusing on cancer prevention efforts. The fact that only 40 % of FAP patients had access to genetic testing stresses the need to promote the establishment of policies supporting genetic testing coverage by medical insurance companies in order to provide patients with the highest standard of care to prevent cancer. Furthermore, our results suggest that Hispanics may have uncommon mutations in adenomatous polyposis related genes, which emphasize the need for full gene sequencing to establish genetic diagnosis.

Dietary patterns and colorectal cancer recurrence and survival: a cohort study

ObjectiveTo examine the association between dietary patterns and colorectal cancer (CRC) survival.DesignCohort study.SettingA familial CRC registry in Newfoundland.Participants529 newly diagnosed CRC patients from Newfoundland. They were recruited from 1999 to...

Síndrome de Lynch: selección de pacientes para el estudio genético mediante análisis de inestabilidad microsatelital e inmunohistoquímica

Selection of patients with Lynch Syndrome (LS) for a genetic study involves the application of clinical criteria. To increase the rate of identification of mutations, the use of molecular studies as Microsatellite Instability (MSI) and Immunohistochemistry (IHC) in the tumor has been proposed. To demonstrate the usefulness of MSI and IHC in the detection of mutations in patients with LS. From our Familial Colorectal Cancer Registry, families suspected of LS were selected according to Amsterdam or Bethesda clinical criteria. Screening of germline mutations of MLH1, MSH2 and MSH6 genes was performed. In addition, analysis of MSI and IHC were performed in colorectal tumors. A total of 35 families were studied (19 met Amsterdam and 16 met Bethesda criteria). Twenty one families harbored a germline alteration in MLH1, MSH2 or MSH6 (18 Amsterdam and 3 Bethesda). In these families, eighteen different alterations were found, 15 of which were mutations and 3 corresponded to variants of uncertain pathogenicity. On the other hand, 80% of the tumors showed positive microsatellite instability (27 MSI-high and 1 MSI-low), and immunohistochemical testing showed that 77% of tumors had the loss of a protein. Correlation between results of tumor molecular studies and the finding of germline nucleotide change showed that IHC and MSI predicted mutations in 81 and 100% of patients, respectively. MSI and IHC can efficiently select patients with a high probability of carrying a mutation in DNA repair genes.

Abstract A68: Familial colorectal cancer registry in Hispanics: A feasibility study

Abstract Background: In Puerto Rico (PR), colorectal cancer (CRC) represents the second most common cause of cancer in men and women. Incidence and mortality of CRC are increasing in Puerto Rican Hispanics, especially among young individuals. Screening rates for CRC are lower in Hispanic-American individuals compared to non-Hispanic patients. However, there is limited data on genetic epidemiological CRC disparities in Hispanic patients. Objectives: (1) To prospectively identify and recruit 30 probands with a family history of CRC and 15 family-history negative. (2) To prospectively identify and recruit selected relatives from the 45 probands. Methods: Eligible cases are Hispanic patients with incident diagnosis of CRC, ≥ 21 years old. We identified the probands and their selected family members using the Puerto Rico Central Cancer Registry from July 1, 2007 to the present. Preliminary data and recruitment: Seven hundred and fifty-one communications were sent to the physicians, three hundred and seventy-four communications were responded (374/751=49.8%). Three hundred and forty-one communications were sent to the patients, one hundred and forty-seven letters were responded (147/341=43.1%) and 16 refused. One hundred and fifty-nine participants (probands and relatives) were enrolled. One-hundred and two probands (mean age 56.9 ± 13.3 yrs., 54.9% male); 30 with and 72 without family history of CRC. At present, we collected 153 (96.2%) risk factors questionnaires, 135 (84.9%) blood samples and 60 (52.6%) blocks of tissue. Successful implementation of logistics for identification of incident CRC through the PR Central Cancer Registry during a three-year period. We established the first Familial CRC island-wide registry in Puerto Rico through the implementation of a network of community physicians, laboratories and professional societies. We are developing a tissue and blood bank with epidemiological, nutritional, and demographic data that will assist us to understand the genetic epidemiology of CRC in Puerto Ricans. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A68.

Abstract 1918: Type 2 diabetes mellitus and colorectal neoplasia risk in Puerto Rican Hispanics: A case-control study

Abstract Background: Epidemiological studies have provided inconclusive evidence regarding the potential link between type 2 diabetes mellitus (DM) and colorectal cancer (CRC).The association between type 2 DM and colorectal neoplasia (colorectal cancer and/or adenomas) has not been well studied in Hispanics, an ethnic minority at high risk for type 2 DM. Objective: To evaluate the association between type 2 DM and colorectal neoplasia (CRN) in Puerto Rican Hispanic adults enrolled in the studies Epidemiology of Loss of Imprinting in Colorectal Cancer, Familial Colorectal Cancer Registry and the Type 2 diabetes mellitus and colorectal neoplasia risk in Hispanics: A case-control study at the VA Caribbean Healthcare System. Methods: The case-control study included patients with incident CRN and controls with negative colonoscopy and without previous history of CRC or adenomas evaluated from January 1, 2005 to December 31, 2009. Diagnosis of type 2 DM was established by previous medical diagnosis and/or anti-diabetic medications use. Unconditional logistic regression was employed to estimate the odds ratio (OR) between type 2 DM and CRN using STATA 10.0. Results: A total of 422 participants (mean age 60.8 ± 12.1 yrs., 61.1% males), prevalence of type 2 DM was 26.3%. 276 patients with CRN and 146 controls were evaluated. In the cases, the prevalence of colorectal adenomas was 25.4% (70/276) and the prevalence of colorectal cancer was 74.6% (206/276). Colorectal neoplasia were mostly adenocarcinomas (60.4%), located in the distal colon (37.3%), and with TNM stage III (21.4%). Cases were mostly men (p=0.01), had lower education (p<0.001) and reported lower use of aspirin (p=0.02) compared to the controls. Cases and controls did not differ by median age (p=0.52), first degree of family history of CRC (p=0.27), first degree of family history of DM (p=0.33) or obesity (p=0.73). There were no statistical significant associations between DM and CRN (OR=1.41; 95% CI: 0.74-2.68), DM and CRC (OR=1.70; 95% CI: 0.74-3.87) or DM and colorectal adenomas (OR=1.04; 95% CI: 0.45-2.42) after adjusting for gender, age, education, aspirin use, obesity and study center. Conclusion: We did not observe a statistical significant association between type 2 DM and CRN. Nonetheless, a tendency towards an increase risk of colorectal neoplasia was observed among type 2 DM patients on adjusted analysis. Possible explanation for our lack of association may be related to high prevalence of type 2 DM in cases and controls and/or the high prevalence of obesity in the study sample. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1918. doi:10.1158/1538-7445.AM2011-1918

Abstract 3767: Familial colorectal cancer registry in Hispanics: A feasibility study

Abstract BACKGROUND: In Puerto Rico (PR), colorectal cancer (CRC) represents the second most common cause of cancer in men and women. Incidence and mortality of CRC are increasing in Puerto Rican Hispanics, especially among young individuals. Screening rates for CRC are lower in Hispanic-American individuals compared to non-Hispanic patients. However, there is limited data on genetic epidemiological CRC disparities in Hispanic patients. OBJECTIVES: (1) To prospectively identify and recruit 30 probands with a family history of CRC and 15 family-history negative (2) To prospectively identify and recruit selected relatives from the 45 probands. METHODS: Eligible cases are Hispanic patients with incident diagnosis of CRC, ≥ 21 years old. We identified the probands and their selected family members using the Puerto Rico Central Cancer Registry from July 1, 2007 to the present. PRELIMINARY DATA AND RECRUITMENT: Seven hundred and fifty-one communications were sent to the physicians, three hundred and seventy-four communications were responded (374/751=49.8%).Three hundred and forty-one communications were sent to the patients, one hundred and forty-seven letters were responded (147/341=43.1%) and 16 refused. One hundred and fifty-nine participants (probands and relatives) were enrolled. One hundred and two probands (mean age 56.9 ±13.3 yrs., 54.9% male); 30 with and 72 without family history of CRC. At present, we collected 153 (96.2%) risk factors questionnaires, 135 (84.9%) blood samples and 60 (52.6%) blocks of tissue. CONCLUSIONS: Successful implementation of logistics for identification of incident CRC through the PR Central Cancer Registry during a three-year period. We established the first Familial CRC island-wide registry in Puerto Rico through the implementation of a network of community physicians, laboratories and professional societies. We are developing a tissue and blood bank with epidemiological, nutritional, and demographic data that will assist us to understand the genetic epidemiology of CRC in Puerto Ricans. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3767. doi:10.1158/1538-7445.AM2011-3767

Cigarette Smoking, Genetic Variants in Carcinogen-metabolizing Enzymes, and Colorectal Cancer Risk

The risk of colorectal cancer associated with smoking is unclear and may be influenced by genetic variation in enzymes that metabolize cigarette carcinogens. The authors examined the colorectal cancer risk associated with smoking and 26 variants in carcinogen metabolism genes in 1,174 colorectal cancer cases and 1,293 population-based controls recruited in Canada by the Ontario Familial Colorectal Cancer Registry from 1997 to 2001. Adjusted odds ratios were calculated by multivariable logistic regression. Smoking for >27 years was associated with a statistically significant increased colorectal cancer risk (adjusted odds ratio (AOR) = 1.25, 95% confidence interval (CI): 1.02, 1.53) in all subjects. Colorectal cancer risk associated with smoking was higher in males for smoking status, duration, and intensity. The CYP1A1-3801-CC (AOR = 0.47, 95% CI: 0.23, 0.94) and CYP2C9-430-CT (AOR = 0.82, 95% CI: 0.68, 0.99) genotypes were associated with decreased risk, and the GSTM1-K173N-CG (AOR = 1.99, 95% CI: 1.21, 3.25) genotype was associated with an increased risk of colorectal cancer. Statistical interactions between smoking and genetic variants were assessed by comparing logistic regression models with and without a multiplicative interaction term. Significant interactions were observed between smoking status and SULT1A1-638 (P = 0.02), NAT2-857 (P = 0.01), and CYP1B1-4390 (P = 0.04) variants and between smoking duration and NAT1-1088 (P = 0.02), SULT1A1-638 (P = 0.04), and NAT1-acetylator (P = 0.03) status. These findings support the hypothesis that prolonged cigarette smoking is associated with increased risk of colorectal cancer and that this risk may be modified by variation in carcinogen metabolism genes.

Spectrum of MLH1 and MSH2 Mutations in Chilean Families With Suspected Lynch Syndrome

Lynch syndrome is the most common inherited syndrome of colorectal cancer, caused principally by germline mutations in MLH1 and MSH2. We report our experience with genetic screening in the diagnosis of Lynch syndrome in Chile, a country previously underserved in the capacity to diagnose hereditary colorectal cancer. Families from our Familial Colorectal Cancer Registry were selected for this study if they fulfilled either Amsterdam I/II or Bethesda criteria for classification of Lynch syndrome. Analysis of colorectal tumors from probands included a microsatellite instability study and immunohistochemical evaluation for MLH1 and MSH2. Screening of germline mutations was performed by single-strand conformation polymorphism analysis and DNA sequencing. A total of 21 families were evaluated, 14 meeting Amsterdam criteria and 7 meeting Bethesda criteria. Tumors in 20 families (95%) showed microsatellite instability (19 high and 1 low) and 9 of these 20 families (45%) harbored a germline mutation (7 of 13 Amsterdam and 2 of 7 Bethesda families). Of the 9 mutations identified, 6 were in MLH1 and 3 in MSH2. Two of the mutations were novel, 3 were previously found in 1 to 2 European populations, and 4 were previously found in various ethnic populations worldwide. Only 2 mutations were previously found in another Latin American population (Colombia). In our probands, colorectal cancer was located mainly (57%) in the right or transverse colon. Pedigree information from 104 family affected members of 21 studied families showed endometrial cancer to be the most frequent primary extracolonic tumor, accounting for 15.1% of total cases, followed by stomach (13.2%) and breast cancer (11.3%). Analysis of mitochondrial DNA haplotypes showed a strong Amerindian genetic component in 15 (71.4%) of the 21 families analyzed. The study of Lynch syndrome in families of different ethnic origins contributes to the definition of genetic and clinical differences among populations. Wide distribution in other ethnic populations strongly suggests varying origins of 4 the mutations found. Although cancer phenotype was consistent with those from other Latin American populations, only 2 of 9 mutations were shared with other South American populations and 2 novel mutations were found. The Chilean population is considered to be an admixture of Amerindian and European-mainly Spanish-populations, producing an ethnic group with significant genetic differences from populations previously studied.

Penetrance of colorectal cancer among MLH1/MSH2 carriers participating in the colorectal cancer familial registry in Ontario

BackgroundSeveral DNA mismatch repair (MMR) genes, responsible for the majority of Lynch Syndrome cancers, have been identified, predominantly MLH1 and MSH2, but the risk associated with these mutations is still not well established. The aim of this study is to provide population-based estimates of the risks of colorectal cancer (CRC) by gender and mutation type from the Ontario population.MethodsWe analyzed 32 families segregating MMR mutations selected from the Ontario Familial Colorectal Cancer Registry and including 199 first-degree and 421 second-degree relatives. The cumulative risks were estimated using a modified segregation-based approach, which allows correction for the ascertainment of the Lynch Syndrome families and permits account to be taken for missing genotype information.ResultsThe risks of developing CRC by age 70 were 60% and 47% among men and women carriers of any MMR mutation, respectively. Among MLH1 mutation carriers, males had significantly higher risks than females at all ages (67% vs. 35% by age 70, p-value = 0.02), while the risks were similar in MSH2 carriers (about 54%). The relative risk associated with MLH1 was almost constant with age (hazard ratio (HR) varied between 5.5-5.1 over age 30–70), while the HR for MSH2 decreased with age (from 13.1 at age 30 to 5.4 at age 70).ConclusionThis study provides a unique population-based study of CRC risks among MSH2/MLH1 mutation carriers in a Canadian population and can help to better define and understand the patterns of risks among members of Lynch Syndrome families.

Family history of hormonal cancers and colorectal cancer risk: A case‐control study conducted in Ontario

Aggregation of cancers among families with highly penetrant genetic mutations such as hereditary nonpolyposis colorectal cancer is well-described. However, there is a paucity of data regarding familial aggregation of hormonal cancers (cancers of the breast, endometrial, ovarian and prostate) and colorectal cancer (CRC) in the general population. We investigated the association between having a first-degree family history of breast, endometrial, ovarian, or prostate cancer and CRC risk. Population-based CRC cases and controls were recruited by the Ontario Familial Colorectal Cancer Registry (OFCCR). Logistic regression was conducted to obtain odds ratio (OR) estimates and 95% confidence intervals (95% CIs). First-degree family history of breast cancer was associated with a modest, borderline statistically significant increased CRC risk (age-, sex-adjusted OR = 1.2, 95% CI = 1.0, 1.5). The magnitude of CRC risk was greatest if more than one first-degree kin had breast cancer (age-, sex-adjusted OR = 1.7, 95% CI = 1.0, 2.0), as well as if the kin was diagnosed at >50 years of age (age-, sex-adjusted OR = 1.4, 95% CI = 1.1, 1.8). Family history of ovarian cancer was associated with reduced CRC risk (multivariate-adjusted OR = 0.6, 95% CI = 0.3, 1.0). Although statistically significant increases in CRC risk were observed in the age-, sex-adjusted OR estimates for family history of endometrial and prostate cancers, the associations were no longer significant after multivariate-adjustment. In conclusion, individuals with a first-degree kin with breast cancer may have a modest increased risk for CRC compared to individuals without.

Allergies are associated with reduced pancreas cancer risk: A population‐based case–control study in Ontario, Canada

Pancreatic adenocarcinoma is one of the deadliest cancers with mortality rates almost equaling incidence rates. Each year, approximately 3,500 Canadians are diagnosed with this disease. Although somewhat inconsistent, epidemiological studies have found that allergies are associated with a reduced pancreas cancer risk while there appears to be no association with asthma. These associations were evaluated in a population-based case-control study conducted in Ontario. Incident cases of pancreatic adenocarcinoma, identified through the Ontario Cancer Registry (OCR), and diagnosed April 1, 2003 to June 1, 2006, were recruited by the Ontario Pancreas Cancer Study (OPCS). Controls were recruited from the Ontario Familial Colorectal Cancer Registry (OFCCR). Data on 276 cases and 378 controls were available for the current study. Multivariable logistic regression analysis was used to obtain age-adjusted odds ratio (AOR) estimates. Ever having allergies or hayfever was associated with reduced pancreas cancer risk (OR = 0.43, 95% confidence interval (CI): 0.29-0.63). There was no association observed between a history of asthma and pancreas cancer risk. Findings are of great importance to understanding the biological mechanisms involved in pancreas cancer development.

Dietary phytoestrogen intake is associated with reduced colorectal cancer risk.

Evidence suggests dietary phytoestrogens may reduce the risk of certain hormonal cancers (e.g. breast and prostate). There is a paucity of data regarding phytoestrogens and colorectal cancer risk. Phytoestrogens are plant compounds with estrogen-like activities. Main classes include isoflavones (found in legumes such as soy) and lignans (found in grains, seeds, nuts, fruits, and vegetables). Although isoflavones have dominated phytoestrogen cancer research, lignans may be more relevant to North American diets. Food questionnaires and analytic databases have recently been modified to incorporate some lignan information. We conducted a case-control study to evaluate the association between phytoestrogen intake and colorectal cancer risk. Colorectal cancer cases were diagnosed in 1997-2000, aged 20-74 y, identified through the population-based Ontario Cancer Registry, and recruited by the Ontario Familial Colorectal Cancer Registry. Controls were a sex and age-group matched random sample of the population of Ontario. Epidemiologic and food frequency questionnaires were completed by 1095 cases and 1890 control subjects. Multivariate logistic regression analysis was used to obtain adjusted odds ratio (OR) estimates. Dietary lignan intake was associated with a significant reduction in colorectal cancer risk [OR (T3 vs. T1) = 0.73; 95% CI: 0.56, 0.94], as was isoflavone intake [OR (T3 vs. T1) = 0.71; 95% CI: 0.58, 0.86]. We evaluated interactions between polymorphic genes that encode enzymes possibly involved in metabolism of phytoestrogens (CYPs, catechol O-methyl transferase, GSTs, and UGTs) and found no significant effect modification with respect to phytoestrogen intake. This finding that phytoestrogen intake may reduce colorectal cancer risk is important, because dietary intake is potentially modifiable.

Colorectal Screening is Associated with Reduced Colorectal Cancer Risk: A Case–Control Study within the Population-Based Ontario Familial Colorectal Cancer Registry

This is the first study to evaluate the association between colonic screening and colorectal cancer risk among Canadians. A case-control study was conducted. Cases were diagnosed with cancer of the colorectum, between 1997 and 2000, aged 20 to 74 years, identified through the population-based Ontario Cancer Registry and recruited by the Ontario Familial Colorectal Cancer Registry. Controls were a sex- and age-matched random sample of the population of Ontario. 971 cases and 1944 controls completed questionnaires (including colorectal screening history and many risk factors). Multivariate logistic regression analysis was used to obtain adjusted odds ratios (OR) estimates. Having had a fecal occult blood screen was associated with reduced colorectal cancer risk (OR=0.76; 95% confidence interval (CI): 0.59, 0.97). Having had a screening sigmoidoscopy was associated with a halving of colorectal cancer risk (OR = 0.52; 95% CI: 0.34, 0.80). Having had a screening colonoscopy did not significantly reduce colorectal cancer risk (OR = 0.69; 95% CI: 0.44, 1.07); however, having had either screening endoscopy was associated with a significant reduction in colorectal cancer risk (OR = 0.62; 95% CI: 0.44, 0.87). Findings differed slightly by anatomic sub-site (proximal and distal colorectum). We report a reduction in colorectal cancer risk among persons who underwent colorectal cancer screening; in particular, sigmoidoscopy. Findings are of great importance for the prevention of colorectal cancer.

263-S: Access to an Educational Colorectal Cancer Website and Subject Participation in the Ontario Familial Colorectal Cancer Registry (OFCCR)

263-S: Access to an Educational Colorectal Cancer Website and Subject Participation in the Ontario Familial Colorectal Cancer Registry (OFCCR)

Association between subject factors and colorectal cancer screening participation in Ontario, Canada

Colorectal cancer screening reduces colorectal cancer incidence and mortality. This population-based study was conducted to evaluate (i) the association between subject factors and colorectal screening participation and (ii) the lifetime prevalence of colorectal screening among the general population of Ontario, Canada. Population-based controls were recruited by the Ontario Familial Colorectal Cancer Registry during 1998–2000. The 1944 persons completed an epidemiologic questionnaire. Descriptive statistics were computed and step-wise multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals. Overall, 23% of persons greater than 50 years of age reported ever having had colorectal cancer screening; 17% reported fecal occult blood test (FOBT), 6% sigmoidoscopy, and 4% colonoscopy. Family history of colorectal cancer, increased age, higher household income, and use of hormone replacement therapy (among women) were all significantly associated with ever having had colorectal cancer screening. The low prevalence of colorectal cancer screening among the target population suggests the need for an increased awareness of the public health importance of colorectal cancer screening.

Body mass index and risk of colon and rectal cancer stratified by tumor location and sex

Purpose The association between body mass index (BMI = weight in kg/height in m 2 ) and colorectal cancer (CRC) risk is complex. It is somewhat established that high BMI is associated with increased risk of cancer in the colon among men, but risk estimates among women vary according to age and menopausal status. There is some evidence suggesting that risk also differs according to tumor subsite (proximal colon, distal colon, rectum) for both men and women, but further studies are needed to confirm the pattern of the association. Here, we examine the association between BMI and CRC risk, stratified according to tumor location in the colon or rectum, and sex. Methods Data for this case–control study were collected from the Ontario Familial Colorectal Cancer Registry. Cases were men and women diagnosed with incident colon or rectal cancer identified through the Ontario Cancer Registry since July 1997. Controls were identified from provincial property assessment files in 2000. Family history was determined through review of a family history questionnaire and reviewed by a genetic counselor for classification. Height and weight 2 years prior were assessed with a self-administered questionnaire. BMI was calculated and categorized according to World Health Organization criteria: low BMI, 2 ; normal, 18.5 to 2 ; overweight, 25 to 2 ; and obese, BMI ≥30 kg/m 2 . Results Among men, an overweight or obese BMI was associated with about a 50% increased risk of colorectal cancer relative to men with a normal BMI. The BMI risk for colorectal cancer was attenuated among premenopausal women, and null for postmenopausal women. Increased risk from overweight and obesity were also found among men, but not women, for proximal and distal subsites of colon cancer. Overweight was associated with increased risk of rectal cancer in women only. Conclusion These results suggest that BMI among men and women is differentially associated with colon and rectal cancer risk. Endogenous or exogenous estrogens may, in part, influence this discordance.

Immunoassay for wild-type protein in lymphocytes predicts germline mutations in patients at risk for hereditary colorectal cancer

Using colorectal cancer (CRC) as an example, we present the hypothesis that quantitative immunoassays for wild-type (full-length) proteins can be used to identify carriers of traits for hereditary diseases. In the case of hereditary CRC, this involves identifying individuals with germline mutations in a mismatch-repair (MMR) gene (mainly hMSH2 or hMLH1) or in the adenomatous polyposis coli (APC) gene. Because expression of wild-type protein should reflect wild-type gene dosage, we predicted that individuals harboring a germline mutation will have a reduction of approximately 50% in expression in lymphocytes of the corresponding full-length protein. In this pilot study, we tested lymphoblastoid cell lines that had been established from controls and individuals with, or at high risk for, hereditary CRC: 9 lines from healthy, unaffected individuals; 4 from affected members in familial adenomatous polyposis families (with known germ-line APC mutation); 42 from CRC patients in our Familial CRC Registry (increased risk of hereditary nonpolyposis colon cancer as assessed by family history, age at adenoma or carcinoma diagnosis, and other clinical criteria). For MSH2 and MLH1 we used western blots; for APC we used immunoprecipitation. All familial adenomatous polyposis lines had about 50% less immunoprecipitable full-length APC protein. Some cell lines (7 of 42) from Familial CRC Registry patients showed on western blots a reduction (mean 46%) in either MSH2 or MLH1 (relative to the other protein). All 7 subsequently were proved to contain a germline MMR mutation. We conclude that (1) because most of the expected CRC-causing germ line mutations are truncation-causing, immunoassays for wild-type protein should be able to identify most individuals with hereditary CRC-causing traits; (2) these assays, which are more practical and inexpensive than current mutation-detecting tests for hereditary CRC traits, have the potential for commercial development into broad-based population screens of high-risk patients and their families and the potential to save both lives and health-care dollars; (3) this strategy may be useful for other hereditary cancers and even other hereditary diseases; (4) our approach has the potential to greatly benefit public-health programs for cancer control.