Cancer in First Nations people in Ontario, Canada: Incidence and mortality, 1991 to 2010.

BACKGROUND: This study aims to measure cancer incidence and mortality rates of Registered First Nations people in Ontario and compare them with those of other people in Ontario from 1991 to 2010. DATA AND METHODS: The federal Indian Register, the Ontario Cancer Registry and the Registered Persons Database were linked to develop a cohort of First Nations people diagnosed with cancer in Ontario. Sex-and site-specific age-standardized cancer incidence and mortality rates, and selected trends over time, were calculated. Rate ratios (RRs) were used to compare rates in First Nations peoples with those of other people in Ontario. RESULTS: The First Nations cohort comprised 194,392 people, with 6,859 cancer diagnoses. First Nations people had higher rates for certain cancers than others in Ontario: lung (males RR 1.19; females RR 1.47), colorectal (males RR 1.36; females RR 1.34) and kidney (males RR1.95; females RR 2.23). While lung cancer rates rose in First Nations females (annual percent change [APC] +2.67), they fell at a similar rate (APC -2.28) in males. Cervical cancer rates fell (APC -9.53) and approached the rate among other females in Ontario. Kidney cancer rates increased in First Nations people. DISCUSSION: First Nations people in Ontario have higher incidence and mortality for certain cancers compared with other people in Ontario. However, the declines in cervical cancer rates in First Nations females and lung cancer rates in First Nations males illustrate the likely impact of Pap test uptake and smoking cessation programs. Community-led efforts to develop culturally appropriate prevention and screening programs are essential to further reduce cancer rates in First Nations people.

Influence of Preexisting Diabetes on Survival After a Breast Cancer Diagnosis in First Nations Women in Ontario, Canada.

PURPOSE: Survival after a breast cancer diagnosis is poorer in First Nations women with a preexisting comorbidity compared with comorbidity-free First Nations women in Ontario, Canada. Given the high prevalence of diabetes in this population, it is important to determine whether preexisting diabetes is related to poorer survival after a breast cancer diagnosis. METHODS: All First Nations women were identified from a cohort of First Nations people diagnosed with breast cancer in diagnostic periods-1995 to 1999 and 2000 to 2004-and seen at a regional cancer program (RCP) in Ontario. Preexisting diabetes status and other factors, such as age at diagnosis, body mass index, and stage at diagnosis, were collected from medical charts at the regional cancer programs. The association between preexisting diabetes and First Nations status was examined by each of the demographic, personal, tumor, and treatment factors using logistic regression models. Survival was compared between First Nations women with (n = 67) and without (n = 215) preexisting diabetes, adjusted by significant study factors using a Cox proportional hazards regression model. RESULTS: The 5-year survival rate among First Nations women with diabetes was 59.8% versus 78.7% among those without diabetes (P < .01). Preexisting diabetes significantly increased the risk of death among First Nations women with breast cancer (hazard ratio, 1.87; 95% CI, 1.12 to 3.13) after adjustment for age group, period of diagnosis, body mass index, other comorbidities at diagnosis, and stage. CONCLUSION: This study recommends awareness of this survival discrepancy among the treatment team for First Nations patients with breast cancer with preexisting diabetes.

A Process Evaluation of the Skin Cancer Prevention Act (Tanning Beds): A Survey of Ontario Public Health Units.

Evidence of the dangers of indoor tanning and its popularity, including among youth, led the Government of Ontario to pass the Skin Cancer Prevention Act (Tanning Beds) (SCPA) in 2014. This legislation includes prohibiting the sale of indoor tanning services to individuals under 18, requiring warning signs be posted, and other safety regulations. We collected information from Ontario Public Health Units to conduct a process evaluation of the SCPA to: understand legislation implementation; assess available evidence about compliance, inspection, and enforcement; and, note barriers and facilitators related to inspection and enforcement. Data was collected March-April 2018. All 36 Ontario Public Health Units were invited to participate in an online questionnaire about the SCPA. Questions covered complaints, inspection, and enforcement, and used both close- and open-ended questions. Participants from 20 Public Health Units responded to the questionnaire; a response rate of 56%. These agencies reported 485 facilities offer indoor tanning. Since 2014, there have been 242 infractions by tanning facility owner/operators related to the SCPA, with most being uncovered during non-mandatory routine inspections (n = 234, 97%), rather than mandatory complaint-based inspections (n = 8, 3%). Most infractions were related to warning signs (n = 201, 83%). No charges were issued for any infractions. Instead, providing education (n = 90, 62%) and issuing warnings (n = 33, 23%) were the most common enforcement strategies. SCPA amendments are needed, including mandatory, routinely scheduled inspections. In addition to providing education, fines may improve compliance. More resources are required for inspection and enforcement of the SCPA.

MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort.

BACKGROUND: Germline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls. METHODS: In this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger. FINDINGS: We analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1·54, 95% CI 1·02-2·33), including when analysis was restricted to patients aged 18 years or younger (1·80, 1·06-3·07). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1·60, 95% CI 1·05-2·44; p=0·04) and Asp294His (2·15, 1·05-4·40; p=0·04). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants. INTERPRETATION: Our pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies. FUNDING: SPD-Pilot/Project-Award-2015; AIRC-MFAG-11831.

Assessing a ban on the use of UV tanning devices among adolescents in Ontario, Canada: first-year results.

OBJECTIVES: To describe the effect of the first year of a ban on UV tanning device (beds, lamps) use among those under 18 years of age in Ontario, Canada. METHODS: Online questionnaires were completed by adolescents in grades 7 to 12, aged less than 18 years: one when the ban was enacted (May 2014) and a second a year later (May 2015). Questionnaires asked grade, age, sex, and about use of UV tanning devices in the previous year. Recent users were asked about length, frequency, and location of use; service refusals and reasons; awareness of signs/warning labels; and use of eye protection. Weighted estimates and confidence intervals were generated. RESULTS: There were 1561 participants in 2014 and 2305 in 2015. No reduction was observed in UV tanning device use (6.9% vs. 7.9%) in the 12 months preceding the survey. In 2015, most respondents used UV tanning devices in beauty establishments, which was a shift away from gyms and fitness centres as seen in 2014. Non-significant increases occurred in the proportions noticing warning signs/labels (57% vs. 71%), required to wear eye protection (92% vs. 99%), and refused service (17% vs. 21%). Most adolescents who were refused service did not use tanning devices that year (72%). CONCLUSION: Use did not change in the year following enactment of a ban on UV tanning devices among youth in Ontario. The ban did lead to improvements in service refusal, awareness of warning signage, and use of eye protection. As service refusal deterred future use, enhanced enforcement is important.

Cancer incidence among First Nations adults in Canada: follow-up of the 1991 Census Mortality Cohort (1992-2009).

OBJECTIVES: Estimate site-specific cancer incidence rates for a wide range of cancers in First Nations adults in Canada, and compare these with rates in non-Aboriginal adults. METHODS: Responses from persons aged 25 and older to the 1991 Long Form Census were linked to national mortality and cancer databases. First Nations- and non-Aboriginal-specific incidence rates were age-standardized to the world standard population. The sex- and site-specific relative risks (RR) of cancer in First Nations compared to those in non-Aboriginal adults were estimated with Poisson regression. Results were stratified by residence on-reserve (all cancers combined) and region of Canada (four most common cancer sites). RESULTS: Compared to non-Aboriginal adults, First Nations had higher incidence of colon and rectum, kidney, cervix, and liver cancers and lower incidence of prostate, breast, bladder, uterus, ovary, and brain cancers, as well as non-Hodgkin lymphoma, leukemia, and melanoma. First Nations women additionally had higher incidence of stomach, gallbladder, and laryngeal cancers and lower incidence of thyroid cancers compared to non-Aboriginal women. The higher relative incidence of stomach and gallbladder cancers was observed only among First Nations adults who reported living on-reserve. Incidence of lung cancer was similar for First Nations and non-Aboriginal adults nationally, though variation by region of Canada was observed. CONCLUSION: First Nations people in Canada have disproportionately high rates of certain cancers, providing evidence to support public health policy and programming. More research is needed to identify factors contributing to the significantly lower incidence observed for various cancer types. Novel methods for studying disparities in cancer incidence among First Nations people are required to support ongoing cancer control planning and advocacy.

Cancer incidence and survival among Métis adults in Canada: results from the Canadian census follow-up cohort (1992-2009).

BACKGROUND: Métis people are 1 of 3 Aboriginal groups recognized by the Canadian constitution. We estimated site-specific incidence rates and survival for the most common cancers among Métis adults in Canada and compared these with rates among non-Aboriginal adults in Canada. METHODS: We examined responses to the 1991 long-form census, including self-reported Métis ancestry linked to national mortality and cancer databases for followup from 1992 to 2009. We estimated age-standardized incidence rates and 5-year relative survival. We determined relative risk (RR) of cancer among Métis and non-Aboriginal adults using Poisson regression, and estimated excess mortality rate ratios using ethnicity-specific life tables. RESULTS: For all cancers and both sexes combined, cancer incidence was similar for Métis and non-Aboriginal adults. However, incidence was significantly higher among Métis adults than among non-Aboriginal adults for the following cancers: female breast (RR 1.18, 95% confidence interval [CI] 1.02-1.37), lung (RR 1.34, 95% CI 1.18-1.52), liver (RR 2.09, 95% CI 1.30-3.38), larynx (RR 1.60, 95% CI 1.03-2.48), gallbladder (RR 2.35, 95% CI 1.12-4.96) and cervix (RR 1.84, 95% CI 1.23-2.76). Métis people had poorer survival for prostate cancer (excess mortality rate ratio 2.60, 95% CI 1.52-4.46). INTERPRETATION: We found higher incidence for several cancers and poorer survival after prostate cancer among Métis adults. Several of these disparities may be related to lifestyle factors (including tobacco use, obesity and lack of cancer screening), providing evidence to support development of public health policy and health care to address cancer burden in the Métis people of Canada.

The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival.

Evidence on the relationship between the vitamin D pathway and outcomes in melanoma is growing, although it is not always clear. We investigated the impact of measured levels of sun exposure at diagnosis on associations of vitamin D receptor gene (VDR) polymorphisms and melanoma death in 3336 incident primary melanoma cases. Interactions between six SNPs and a common 3'-end haplotype were significant (p < .05). These SNPs, and a haplotype, had a statistically significant association with survival among subjects exposed to high UVB in multivariable regression models and exerted their effect in the opposite direction among those with low UVB. SNPs rs1544410/BsmI and rs731236/TaqI remained significant after adjustment for multiple testing. These results suggest that the association between VDR and melanoma-specific survival is modified by sun exposure around diagnosis, and require validation in an independent study. Whether the observed effects are dependent or independent of vitamin D activation remains to be determined.

Choice of relative or cause-specific approach to cancer survival analysis impacts estimates differentially by cancer type, population, and application: evidence from a Canadian population-based cohort study.

BACKGROUND: Cause-specific (CS) and net survival in a relative survival framework (RS) are two of the most common methods for estimating cancer survival. In this paper, we assess the differences in results produced by two permutations of cause-specific and relative survival applied to estimating cancer survival and disparities in cancer survival, using data from First Nations and non-Aboriginal populations in Canada. METHODS: Subjects were members of the 1991 Canadian Census Mortality Cohort, a population-based cohort of adult respondents to the 1991 Long Form Census who have been followed up for incident cancers and death through linkage to administrative databases. We compared four methods: relative survival analyses with ethnicity-specific life tables (RS-ELT); relative survival with general population life tables (RS-GLT); cause-specific survival with a broad definition of cancer death (CS-Broad); and cause-specific survival with a narrow definition of cause of death (CS-Narrow) and applied these to the nine most common cancers among First Nations. RESULTS: Apart from breast and prostate cancers, RS-ELT, RS-GLT, and CS-Broad tended to produce similar estimates of age-standardized five-year survival, whereas CS-Narrow yielded higher estimates of survival. CS-Narrow estimates were particularly unlike those based on the other methods for cancers of the digestive and respiratory tracts. Estimates of disparities in survival were generally comparable across the four methods except for breast and prostate cancers. CONCLUSIONS: Cancer surveillance efforts in sub-populations defined by race, ethnicity, geography, socioeconomic status, or similar factors are necessary for identifying disparities and monitoring progress toward reducing them. In the absence of routine monitoring of cancer survival and cancer survival disparities in these populations, estimates generated by different methods will inevitably be compared over time and across populations. In this study, we demonstrate that caution should be exercised in making these comparisons, particularly in interpreting cause-specific survival rates with an unknown or narrow definition of cancer death and in estimates of breast and prostate cancer survival and/or disparities in survival generated by different methods.

Cancer risk factors and screening in First Nations in Ontario. / Facteurs de risque et dépistage du cancer chez les Premières Nations en Ontario.

INTRODUCTION: A lack of identifiers in health administrative databases limits our understanding of the cancer burden in First Nations. This study compares cancer risk factors and screening between First Nations in Ontario (on and off reserve) and non-Aboriginal Ontarians using two unique health surveys. METHODS: We measured age-standardized prevalence estimates using the First Nations Regional Health Survey (RHS) Phase 2, 2008/10 (for First Nations on reserve) and the Canadian Community Health Survey (CCHS), 2007-2013 (for First Nations off reserve and non-Aboriginal Ontarians). We used prevalence rate ratios (RR) and Pearson's chisquare tests for differences in proportions to compare estimates between First Nations (on and off reserve) and non-Aboriginal Ontarians. RESULTS: A higher proportion of First Nation men, women and adolescents on reserve smoked (RR = 1.97, 2.78 and 7.21 respectively) and were obese (RR = 1.73, 2.33 and 3.29 respectively) compared to their non-Aboriginal counterparts. Similar patterns were observed for First Nations off reserve. Frequent binge drinking was also more prevalent among First Nation men and women living on reserve (RR = 1.28 and 2.22, respectively) and off reserve (RR = 1.70 and 1.45, respectively) than non-Aboriginal Ontarians. First Nation men and women on reserve were about half as likely to consume fruit at least twice per day and vegetables at least twice per day compared to non-Aboriginal men and women (RR = 0.53 and 0.54, respectively). Pap test uptake was similar across all groups, while First Nation women on reserve were less likely to have had a mammogram in the last five years than non-Aboriginal women (RR = 0.85). CONCLUSION: First Nations, especially those living on reserve, have an increased risk for cancer and other chronic diseases compared to non-Aboriginal Ontarians. These results provide evidence to support policies and programs to reduce the future burden of cancer and other chronic diseases in First Nations in Ontario.

INTRODUCTION: L'absence d'identificateurs, dans les bases de données administratives sur la santé, nous empêche de bien comprendre le fardeau du cancer chez les Premières Nations. Notre étude compare les facteurs de risque et le dépistage du cancer chez les membres des Premières Nations en Ontario (vivant dans des réserves et hors réserves) et chez les Ontariens non autochtones, en s'appuyant sur deux enquêtes sur la santé. MÉTHODOLOGIE: L'absence d'identificateurs, dans les bases de données administratives sur la santé, nous empêche de bien comprendre le fardeau du cancer chez les Premières Nations. Notre étude compare les facteurs de risque et le dépistage du cancer chez les membres des Premières Nations en Ontario (vivant dans des réserves et hors réserves) et chez les Ontariens non autochtones, en s'appuyant sur deux enquêtes sur la santé. RÉSULTATS: Une proportion plus élevée d'hommes, de femmes et d'adolescents des Premières Nations vivant dans des réserves fumaient (RT = 1,97, 2,78 et 7,21 respectivement) et souffraient d'obésité (RT = 1,73, 2,33 et 3,29 respectivement), comparativement à leurs homologues non autochtones. Des tendances similaires ont été observées chez les membres des Premières Nations vivant hors réserves. La consommation excessive ponctuelle d'alcool fréquente était également plus répandue chez les hommes et les femmes des Premières Nations vivant dans des réserves (RT = 1,28 et 2,22, respectivement) et hors réserves (RT = 1,70 et 1,45, respectivement) que chez les Ontariens non autochtones. Les hommes et les femmes des Premières Nations vivant dans des réserves étaient deux fois moins susceptibles de consommer des fruits au moins deux fois par jour et des légumes au moins deux fois par jour que les hommes et les femmes non autochtones (RT = 0,53 et 0,54, respectivement). La participation au test de Pap était similaire dans tous les groupes, mais les femmes des Premières Nations étaient moins susceptibles que les femmes non autochtones (RT = 0,85) d'avoir subi une mammographie au cours des cinq années précédant l'enquête. CONCLUSION: Comparativement aux Ontariens non autochtones, les membres des Premières Nations, en particulier ceux qui vivent dans une réserve, présentent un risque accru de cancer et d'autres maladies chroniques. Ces résultats fournissent des éléments probants à l'appui de politiques et de programmes visant à réduire le fardeau futur du cancer et d'autres maladies chroniques chez les Premières Nations en Ontario.

Cancer Survival Disparities Between First Nation and Non-Aboriginal Adults in Canada: Follow-up of the 1991 Census Mortality Cohort.

BACKGROUND: The burden of cancer among indigenous people in Canada has been understudied due to a lack of ethnic identifiers in cancer registries. We compared cancer survival among First Nations to that among non-Aboriginal adults in Canada in the first national study of its kind to date. METHODS: A population-based cohort of approximately 2 million respondents to the 1991 Canadian Long Form Census was followed for cancer diagnoses and deaths using probabilistic linkage to cancer and death registries until 2009. Excess mortality rate ratios (EMRR) and 5-year age-standardized relative survival rates were calculated for 15 cancers using age, sex, ethnicity, and calendar-time-specific life tables derived from the cohort at large. RESULTS: First Nations diagnosed with cancers of the colon and rectum, lung and bronchus, breast, prostate, oral cavity and pharynx, cervix, ovary, or with non-Hodgkin lymphoma and leukemia all had significantly poorer 5-year survival than their non-Aboriginal peers. For colorectal cancer, a significant disparity was only present between 2001 and 2009 (EMRR: 1.52; 95% CI, 1.28-1.80). For prostate cancer, a significant disparity was only present between 1992 and 2000 (EMRR: 2.76; 95% CI, 1.81-4.21). Adjusting for income and rurality had little impact on the EMRRs. CONCLUSIONS: Compared with non-Aboriginals, First Nations people had poorer survival for 14 of 15 of the most common cancers, and disparities could not be explained by income and rurality. IMPACT: The results of this study can serve as a benchmark for monitoring progress toward narrowing the gap in survival. Cancer Epidemiol Biomarkers Prev; 26(1); 145-51. ©2016 AACR.

Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study.

Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0.47; 95% Confidence Intervals (CI) = 0.27-0.81, P = 0.02) and a decrease in Breslow thickness (P = 0.03). The ATG16L heterozygous genotype (AG) (rs2241880) was associated with younger age at diagnosis (P = 0.02). Two SNPs in ATG5 were found to be associated with increased stage (rs2245214 CG, OR 1.47; 95% CI = 1.11-1.94, P = 0.03; rs510432 CC, OR 1.84; 95% CI = 1.12-3.02, P = 0.05). Finally, we identified inverse associations between ATG5 (GG rs2245214) and melanomas on the scalp or neck (OR 0.20, 95% CI = 0.05-0.86, P = 0.03); ATG10 (CC) (rs1864182) and brisk tumor infiltrating lymphocytes (TILs) (OR 0.42; 95% CI = 0.21-0.88, P = 0.02), and ATG5 (CC) (rs510432) with nonbrisk TILs (OR 0.55; 95% CI = 0.34-0.87, P = 0.01). Our data suggest that ATG SNPs might be differentially associated with specific host and tumor characteristics including age at diagnosis, TILs, and stage. These associations may be critical to understanding the role of autophagy in cancer, and further investigation will help characterize the contribution of these variants to melanoma progression.

Association of Interferon Regulatory Factor-4 Polymorphism rs12203592 With Divergent Melanoma Pathways.

BACKGROUND: Solar elastosis and neval remnants are histologic markers characteristic of divergent melanoma pathways linked to differences in age at onset, host phenotype, and sun exposure. However, the association between these pathway markers and newly identified low-penetrance melanoma susceptibility loci remains unknown. METHODS: In the Genes, Environment and Melanoma (GEM) Study, 2103 Caucasian participants had first primary melanomas that underwent centralized pathology review. For 47 single-nucleotide polymorphisms (SNPs) previously identified as low-penetrant melanoma risk variants, we used multinomial logistic regression to compare melanoma with solar elastosis and melanoma with neval remnants simultaneously to melanoma with neither of these markers, excluding melanomas with both markers. All statistical tests were two-sided. RESULTS: IRF4 rs12203592 was the only SNP to pass the false discovery threshold in baseline models adjusted for age, sex, and study center. rs12203592*T was associated positively with melanoma with solar elastosis (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.18 to 1.82) and inversely with melanoma with neval remnants (OR = 0.65, 95% CI = 0.48 to 0.87) compared with melanoma with neither marker (P global = 3.78 x 10(-08)). Adjusting for phenotypic characteristics and total sun exposure hours did not materially affect rs12203592's associations. Distinct early- and late-onset age distributions were observed in patients with IRF4 rs12203592 [CC] and [TT] genotypes, respectively. CONCLUSIONS: Our findings suggest a role of IRF4 rs12203592 in pathway-specific risk for melanoma development. We hypothesize that IRF4 rs12203592 could underlie in part the bimodal age distribution reported for melanoma and linked to the divergent pathways.

An update to the recommended core content for sun safety messages for public education in Canada: A consensus report.

Reducing ultraviolet radiation exposure decreases the risk of skin cancer and eye damage. Between 1996 and 2006, Canadians increased their time in the sun without improving protection. National consensus on sun protection information for the public was last achieved in 1994. Public messages have since been modified inconsistently. The Ontario Sun Safety Working Group initiated a review of messages and engaged a scientific panel to draft message content. Working Group members then delivered a national consensus process, engaging a National Steering Committee, a health communications expert and representatives from 28 organizations through a workshop with pre- and post-workshop surveys. The result of the consensus process is the updated Recommended Core Content for Sun Safety Messages in Canada. Four groups of statements comprise the new content: Key Facts, Primary Recommended Protective Action Statements, Additional Recommended Protective Action Statements, and Tips for Implementing the Primary Protective Actions. Organizations are encouraged to adopt, at minimum, the Primary Recommended Protective Action Statements as the basis for public messaging. The recommended core content establishes a common understanding of what is needed for effective sun protection. The underlying expectation is that, as a key next step, content will be tailored for different subpopulations and health promotion campaigns.

Vitamin D receptor polymorphisms and survival in patients with cutaneous melanoma: a population-based study.

Factors known to affect melanoma survival include age at presentation, sex and tumor characteristics. Polymorphisms also appear to modulate survival following diagnosis. Result from other studies suggest that vitamin D receptor (VDR) polymorphisms (SNPs) impact survival in patients with glioma, renal cell carcinoma, lung, breast, prostate and other cancers; however, a comprehensive study of VDR polymorphisms and melanoma-specific survival is lacking. We aimed to investigate whether VDR genetic variation influences survival in patients with cutaneous melanoma. The analysis involved 3566 incident single and multiple primary melanoma cases enrolled in the international population-based Genes, Environment, and Melanoma Study. Melanoma-specific survival outcomes were calculated for each of 38 VDR SNPs using a competing risk analysis after adjustment for covariates. There were 254 (7.1%) deaths due to melanoma during the median 7.6 years follow-up period. VDR SNPs rs7299460, rs3782905, rs2239182, rs12370156, rs2238140, rs7305032, rs1544410 (BsmI) and rs731236 (TaqI) each had a statistically significant (trend P values < 0.05) association with melanoma-specific survival in multivariate analysis. One functional SNP (rs2239182) remained significant after adjustment for multiple testing using the Monte Carlo method. None of the SNPs associated with survival were significantly associated with Breslow thickness, ulceration or mitosis. These results suggest that the VDR gene may influence survival from melanoma, although the mechanism by which VDR exerts its effect does not seem driven by tumor aggressiveness. Further investigations are needed to confirm our results and to understand the relationship between VDR and survival in the combined context of tumor and host characteristics.

Inherited genetic variants associated with occurrence of multiple primary melanoma.

Recent studies, including genome-wide association studies, have identified several putative low-penetrance susceptibility loci for melanoma. We sought to determine their generalizability to genetic predisposition for multiple primary melanoma in the international population-based Genes, Environment, and Melanoma (GEM) Study. GEM is a case-control study of 1,206 incident cases of multiple primary melanoma and 2,469 incident first primary melanoma participants as the control group. We investigated the odds of developing multiple primary melanoma for 47 SNPs from 21 distinct genetic regions previously reported to be associated with melanoma. ORs and 95% confidence intervals were determined using logistic regression models adjusted for baseline features (age, sex, age by sex interaction, and study center). We investigated univariable models and built multivariable models to assess independent effects of SNPs. Eleven SNPs in 6 gene neighborhoods (TERT/CLPTM1L, TYRP1, MTAP, TYR, NCOA6, and MX2) and a PARP1 haplotype were associated with multiple primary melanoma. In a multivariable model that included only the most statistically significant findings from univariable modeling and adjusted for pigmentary phenotype, back nevi, and baseline features, we found TERT/CLPTM1L rs401681 (P = 0.004), TYRP1 rs2733832 (P = 0.006), MTAP rs1335510 (P = 0.0005), TYR rs10830253 (P = 0.003), and MX2 rs45430 (P = 0.008) to be significantly associated with multiple primary melanoma, while NCOA6 rs4911442 approached significance (P = 0.06). The GEM Study provides additional evidence for the relevance of these genetic regions to melanoma risk and estimates the magnitude of the observed genetic effect on development of subsequent primary melanoma.

Colorectal cancer incidence in the Aboriginal population of Ontario, 1998 to 2009.

BACKGROUND: Studies suggest that colorectal cancer incidence increased disproportionately among the Aboriginal population of Ontario relative to the general population. Using an ecological approach, this study examined colorectal cancer incidence for the 1998-to-2009 period among Aboriginal people living in Ontario. DATA AND METHODS: Based on their postal code when they were diagnosed, cases of colorectal cancer identified from the Ontario Cancer Registry were assigned to census geographic areas with high (33% or more) or low percentages of Aboriginal identity residents, using the Postal Code Conversion File Plus (PCCF+). To account for potential misclassification by the PCCF+, Indian reserves for which assignment through postal codes is likely to be accurate were identified. Age-standardized incidence rates and rate ratios were calculated to compare colorectal cancer incidence in high-Aboriginal identity areas or on Indian reserves with incidence in low-Aboriginal identity areas. RESULTS: Colorectal cancer incidence was significantly higher for residents of high- versus low-Aboriginal identity areas in Ontario (rate ratio for men = 1.44, 95% CI = 1.26-1.63; rate ratio for women = 1.42, 95% CI = 1.23-1.63), a disparity that persisted by age group. When the Aboriginal sample was limited to residents of Indian reserves, the difference was statistically significant only for men and for people aged 50 to 74. INTERPRETATION: The incidence of colorectal cancer differs across areas of Ontario with high and low percentages of Aboriginal identity residents.