Search

The article describes the rationale for the challenges involved and methods being used in strategic partnership Canadian Partnership for Tomorrow Project's cohort for the study of the causes of cancer and other chronic diseases in Canada. The aim is to understand the role of environment, lifestyle and genetics in development of chronic diseases. To provide the foundation for hundreds of studies, data collection methods include physical measurements, urine and blood samples and questionnaires.

Editorial. Focuses on the impact of alcohol on public health. Reference to a report by Thun et al in same magazine; Issues arising from the findings, such as the question of alcohol being the preventive therapy of choice in cardiovascular disease, affecting the interpretation of the results and generalizations; The suggestion of moderation in temperance.

Introduction: Indigenous people have disproportionally worse health and lower life expectancy than their non-indigenous counterparts in high-income countries. Cancer data for indigenous people are scarce and incidence has not previously been collectively reported in Australia, New Zealand, Canada, and the USA. We aimed to investigate and compare, for the first time, the cancer burden in indigenous populations in these countries.Methods: We derived incidence data from population-based cancer registries in three states of Australia (Queensland, Western Australia, and the Northern Territory), New Zealand, the province of Alberta in Canada, and the Contract Health Service Delivery Areas of the USA. Summary rates for First Nations and Inuit in Alberta, Canada, were provided directly by Alberta Health Services. We compared age-standardised rates by registry, sex, cancer site, and ethnicity for all incident cancer cases, excluding non-melanoma skin cancers, diagnosed between 2002 and 2006. Standardised rate ratios (SRRs) and 95% CIs were computed to compare the indigenous and non-indigenous populations of each jurisdiction, except for the Alaska Native population, which was compared with the white population from the USA.Findings: We included 24 815 cases of cancer in indigenous people and 5 685 264 in non-indigenous people from all jurisdictions, not including Alberta, Canada. The overall cancer burden in indigenous populations was substantially lower in the USA except in Alaska, similar or slightly lower in Australia and Canada, and higher in New Zealand compared with their non-indigenous counterparts. Among the most commonly occurring cancers in indigenous men were lung, prostate, and colorectal cancer. In most jurisdictions, breast cancer was the most common cancer in women followed by lung and colorectal cancer. The incidence of lung cancer was higher in indigenous men in all Australian regions, in Alberta, and in US Alaska Natives than in their non-indigenous counterparts. For breast cancer, rates in women were lower in all indigenous populations except in New Zealand (SRR 1·23, CI 95% 1·16-1·32) and Alaska (1·14, 1·01-1·30). Incidence of cervical cancer was higher in indigenous women than in non-indigenous women in most jurisdictions, although the difference was not always statistically significant.Interpretation: There are clear differences in the scale and profile of cancer in indigenous and non-indigenous populations in Australia, New Zealand, Canada, and the USA. Our findings highlight the need for much-improved, targeted programmes of screening, vaccination, and smoking cessation, among other prevention strategies. Governments and researchers need to work in partnership with indigenous communities to improve cancer surveillance in all jurisdictions and facilitate access to cancer data.Funding: International Agency for Research on Cancer-Australia Fellowship. [ABSTRACT FROM AUTHOR]

Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05). Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001). Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively), however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68-0.86; rs1105879 OR = 0.77 95% CI = 0.69-0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively), with the direction of association similar to that observed for CRC. Additionally, they showed interaction between any non-steroidal anti-inflammatory drugs (including aspirin) use and CRC risk (Pinteraction = 0.01 for both). All gene x environment (GxE) interactions however were not significant after multiple test correction. Candidate gene investigation indicated no evidence of GxE interaction between genetic variants in genes involved in aspirin pathways, regular aspirin use and colorectal cancer risk.

Importance: Li-Fraumeni syndrome, usually characterized by germline TP53 mutations, is associated with markedly elevated lifetime risks of multiple cancers, and has been linked to an increased risk of early-onset colorectal cancer., Objective: To examine the frequency of germline TP53 alterations in patients with early-onset colorectal cancer., Design, Setting, and Participants: This was a multicenter cross-sectional cohort study of individuals recruited to the Colon Cancer Family Registry (CCFR) from 1998 through 2007 (genetic testing data updated as of January 2015). Both population-based and clinic-based patients in the United States, Canada, Australia, and New Zealand were recruited to the CCFR. Demographic information, clinical history, and family history data were obtained at enrollment. Biospecimens were collected from consenting probands and families, including microsatellite instability and DNA mismatch repair immunohistochemistry results. A total of a 510 individuals diagnosed as having colorectal cancer at age 40 years or younger and lacking a known hereditary cancer syndrome were identified from the CCFR as being potentially eligible. Fifty-three participants were excluded owing to subsequent identification of germline mutations in DNA mismatch repair genes (n = 47) or biallelic MUTYH mutations (n = 6)., Interventions: Germline sequencing of the TP53 gene was performed. Identified TP53 alterations were assessed for pathogenicity using literature and international mutation database searches and in silico prediction models., Main Outcomes and Measures: Frequency of nonsynonymous germline TP53 alterations., Results: Among 457 eligible participants (314, population-based; 143, clinic-based; median age at diagnosis, 36 years [range, 15-40 years]), 6 (1.3%; 95% CI, 0.5%-2.8%) carried germline missense TP53 alterations, none of whom met clinical criteria for Li-Fraumeni syndrome. Four of the identified TP53 alterations have been previously described in the literature in probands with clinical features of Li-Fraumeni syndrome, and 2 were novel alterations., Conclusions and Relevance: In a large cohort of patients with early-onset colorectal cancer, germline TP53 mutations were detected at a frequency comparable with the published prevalence of germline APC mutations in colorectal cancer. With the increasing use of multigene next-generation sequencing panels in hereditary cancer risk assessment, clinicians will be faced with the challenge of interpreting the biologic and clinical significance of germline TP53 mutations in families whose phenotypes are atypical for Li-Fraumeni syndrome.

Background: Family studies have served as a cornerstone of genetic research on colorectal cancer., Materials and Methods: The Colorectal Cancer Family Registry (Colon CFR) is an international consortium of six centers in North America and Australia formed as a resource to support studies on the etiology, prevention, and clinical management of colorectal cancer. Differences in design and sampling schemes ensures a resource that covers the continuum of disease risk. Two separate recruitment strategies identified colorectal cancer cases: population-based (incident case probands identified by cancer registries; all six centers) and clinic-based (families with multiple cases of colorectal cancer presenting at cancer family clinics; three centers). At this time, the Colon CFR is in year 10 with the second phase of enrollment nearly complete. In phase I recruitment (1998-2002), population-based sampling ranged from all incident cases of colorectal cancer to a subsample based on age at diagnosis and/or family cancer history. During phase II (2002-2007), population-based recruitment targeted cases diagnosed before the age of 50 years are more likely attributable to genetic factors. Standardized protocols were used to collect information regarding family cancer history and colorectal cancer risk factors, and biospecimens were obtained to assess microsatellite instability (MSI) status, expression of mismatch repair proteins, and other molecular and genetic processes., Results: Of the 8,369 case probands enrolled to date, 2,602 reported having one or more colorectal cancer-affected relatives and 799 met the Amsterdam I criteria for Lynch syndrome. A large number of affected (1,324) and unaffected (19,816) relatives were enrolled, as were population-based (4,108) and spouse (983) controls. To date, 91% of case probands provided blood (or, for a few, buccal cell) samples and 75% provided tumor tissue. For a selected sample of high-risk subjects, lymphocytes have been immortalized. Nearly 600 case probands had more than two affected colorectal cancer relatives, and 800 meeting the Amsterdam I criteria and 128, the Amsterdam II criteria. MSI testing for 10 markers was attempted on all obtained tumors. Of the 4,011 tumors collected in phase I that were successfully tested, 16% were MSI-high, 12% were MSI-low, and 72% were microsatellite stable. Tumor tissues from clinic-based cases were twice as likely as population-based cases to be MSI-high (34% versus 17%). Seventeen percent of phase I proband tumors and 24% of phase II proband tumors had some loss of mismatch repair protein, with the prevalence depending on sampling. Active follow-up to update personal and family histories, new neoplasms, and deaths in probands and relatives is nearly complete., Conclusions: The Colon CFR supports an evolving research program that is broad and interdisciplinary. The greater scientific community has access to this large and well-characterized resource for studies of colorectal cancer.

Background: Increased attention has been directed toward the long-term health outcomes of survivors of childhood cancer. To facilitate such research, a multi-institutional consortium established the Childhood Cancer Survivor Study (CCSS), a large, diverse, and well-characterized cohort of 5-year survivors of childhood and adolescent cancer., Procedure: Eligibility for the CCSS cohort included a selected group of cancer diagnoses prior to age 21 years between 1970-1986 and survival for at least 5 years., Results: A total of 20,276 eligible subjects were identified from the 25 contributing institutions, of whom 15% are considered lost to follow-up. Currently, 14,054 subjects (69.3% of the eligible cohort) have participated by completing a 24-page baseline questionnaire. The distribution of first diagnoses includes leukemia (33%), lymphoma (21%), neuroblastoma (7%), CNS tumor (13%), bone tumor (8%), kidney tumor (9%), and soft-tissue sarcoma (9%). Abstraction of medical records for chemotherapy, radiation therapy, and surgical procedures has been successfully completed for 98% of study participants. Overall, 78% received radiotherapy and 73% chemotherapy., Conclusion: The CCSS represents the largest and most extensively characterized cohort of childhood and adolescent cancer survivors in North America. It serves as a resource for addressing important issues such as risk of second malignancies, endocrine and reproductive outcome, cardiopulmonary complications, and psychosocial implications, among this unique and ever-growing population., (Copyright 2002 Wiley-Liss, Inc.)