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Loraine D Marrett

Publications and source records attributed to Loraine D Marrett.

At least 19 recordsLinked to original sources
PubMed2016

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.

Adult↗
PubMed2007

Decreasing incidence of cervical adenocarcinoma in Ontario: is this related to improved endocervical Pap test sampling?

In many developed countries, the incidence of cervical cancer has decreased. These reductions have been specific to squamous cell carcinoma (SCC) and have not included adenocarcinoma (AC). Incidence of AC has increased steadily over the last 20 years. The intent of this article is to examine trends in cervical adenocarcinoma incidence in Ontario over a 20-year period in relation to screening practices. All cases of cervical cancer between 1981 and 2002 were extracted from the Ontario Cancer Registry (a population-based, provincial-wide database). Age-standardized incidence rates were calculated overall, by broad age groups and by morphological type (SCC and AC). Time trends were assessed using JoinPoint methodology. In Ontario, opportunistic cervical cancer screening has been accompanied by significantly decreased rates of SCC since at least 1981. Conversely, the incidence of AC rose by 3.1% per year (95% CI: 1.6%, 4.6%) between 1981 and 1995, and subsequently declined by 4.0% per year (95% CI: -7.4%, -0.5%). From the mid- to late-1990s, instructions were distributed to clinicians, reinforcing the importance of dual specimen collection (i.e., using both spatula and endocervical brush). At the same time, laboratories routinely provided physicians with kits that included both spatula and brush. The subsequent decline in AC incidence may be due, in part, to improved specimen collection. As well, the decline may be partly due to increased awareness of AC precursors among cytopathologists and clinicians, and/or improvements in laboratory training and quality assurance.

Adenocarcinoma↗
PubMed2007

CDKN2A germline mutations in individuals with cutaneous malignant melanoma.

Cyclin-dependent kinase inhibitor type 2A (CDKN2A) has been identified as a major melanoma susceptibility gene based on the presence of germline mutations in high-risk melanoma families. In this study, we sought to identify and characterize the spectrum of CDKN2A mutations affecting p16 inhibitor of cyclin-dependent kinase type 4 (INK4a) in individuals with melanoma using a population-based study design. DNA samples from 1189 individuals with incident multiple primary melanoma (MPM) and 2424 with incident single primary melanoma unselected for family history of melanoma were available for screening of CDKN2A (p16INK4a) mutations. Variants were classified for functional impact based on intragenic position, existing functional data, sequence, and structural analysis. The impact of individual mutations and functional groupings was assessed by comparing frequencies in cases of MPM versus cases with a single first primary melanoma, and by comparing the reported incidence rates in first-degree relatives. Our results show that mutations occur infrequently in these high-risk groups, and that they occur mainly in exons 1alpha and 2. Rare coding variants with putative functional impact are observed to increase substantially the risk of melanoma. With the exception of the variant in position -34 of CDKN2A of known functional consequence, the remaining rare variants in the non-coding region have no apparent impact on risk.

Cyclin-Dependent Kinase Inhibitor p16↗
PubMed2007

Ambient UV, personal sun exposure and risk of multiple primary melanomas.

OBJECTIVE: Sun exposure is the main cause of melanoma in populations of European origin. No previous study has examined the effect of sun exposure on risk of multiple primary melanomas compared with people who have one melanoma. METHODS: We identified and enrolled 2,023 people with a first primary melanoma (controls) and 1,125 with multiple primary melanomas (cases) in seven centers in four countries, recorded their residential history to assign ambient UV and interviewed them about their sun exposure. RESULTS: Risk of multiple primary melanomas increased significantly (P<0.05) to OR=2.10 for the highest exposure quarter of ambient UV irradiance at birth and 10 years of age, to OR=1.38 for lifetime recreational sun exposure, to OR=1.85 for beach and waterside activities, to OR=1.57 for vacations in a sunnier climate, to OR=1.50 for sunburns. Occupational sun exposure did not increase risk (OR=1.03 for highest exposure). Recreational exposure at any age increased risk and appeared to add to risk from ambient UV in early life. CONCLUSIONS: People who have had a melanoma can expect to reduce their risk of a further melanoma by reducing recreational sun exposure whatever their age. The same is probably true for a person who has never had a melanoma.

Adolescent↗
PubMed2006

Population-based study of natural variation in the melanocortin-1 receptor gene and melanoma.

Natural variation in the coding region of the melanocortin-1 receptor (MC1R) gene is associated with constitutive pigmentation phenotypes and development of melanoma and nonmelanoma skin cancers. We investigated the effect of MC1R variants on melanoma using a large, international population-based study design with complete determination of all MC1R coding region variants. Direct sequencing was completed for 2,202 subjects with a single primary melanoma (controls) and 1,099 subjects with second or higher-order primary melanomas (cases) from Australia, the United States, Canada, and Italy. We observed 85 different MC1R variants, 10 of which occurred at a frequency >1%. Compared with controls, cases were more likely to carry two previously identified red hair ("R") variants [D84E, R151C, R160W, and D294H; odds ratio (OR), 1.6; 95% confidence interval (95% CI), 1.1-2.2]. This effect was similar among individuals carrying one R variant and one r variant (defined as any non-R MC1R variant; OR, 1.6; 95% CI, 1.3-2.2) and among those carrying only one R variant (OR, 1.5; 95% CI, 1.1-1.9). There was no statistically significant association among those carrying only one or two r variants. Effects were similar across geographic regions and categories of pigmentation characteristics or number of moles. Our results confirm that MC1R is a low-penetrance susceptibility locus for melanoma, show that pigmentation characteristics may not modify the relationship of MC1R variants and melanoma risk, and suggest that associations may be smaller than previously reported in part due to the study design.

Adult↗
PubMed2006

A design for cancer case-control studies using only incident cases: experience with the GEM study of melanoma.

BACKGROUND: The population-based case-control study is not suited to the evaluation of rare genetic (or environmental) factors. The use of a novel case-control design in which cases have second primaries and controls are cancer survivors has been proposed for this purpose. METHODS: We report results from an international study of melanoma that involved population-based ascertainment of incident cases of second or subsequent primary melanoma as the 'case' group and incident cases of first primary melanoma as the 'control' group. We evaluate the validity of the study design by comparing the results obtained for phenotypic factors that have been shown consistently to be associated with melanoma in previous conventional studies with the results from a conventional case-control study conducted in Connecticut and from literature reviews. RESULTS: All but one of the known risk factors for melanoma were shown to be significantly associated with melanoma in our study, though the individual odds ratios appear to be somewhat attenuated relative to the magnitudes typically observed in the literature. CONCLUSIONS: Patients with a second or subsequent primary cancer of a single type represent a potentially valuable and under-utilized resource for the study of cancer aetiology.

Adult↗
PubMed2006

The prevalence of CDKN2A germ-line mutations and relative risk for cutaneous malignant melanoma: an international population-based study.

Germ-line mutations of CDKN2A have been identified as strong risk factors for melanoma in studies of multiple-case families. However, an assessment of their relative risk for melanoma in the general population has been difficult because they occur infrequently. We addressed this issue using a novel population-based case-control study design in which "cases" have incident second- or higher-order melanomas [multiple primary melanoma (MPM)] and "controls" have incident first primary melanoma [single primary melanoma (SPM)]. Participants were ascertained from nine geographic regions in Australia, Canada, Italy, and United States. In the 1,189 MPM cases and 2,424 SPM controls who were eligible and available for analysis, the relative risk of a subsequent melanoma among patients with functional mutations who have an existing diagnosis of melanoma, after adjustments for age, sex, center, and known phenotypic risk factors, is estimated to be 4.3 (95% confidence interval, 2.3-7.7). The odds ratio varied significantly depending on the type of mutation involved. The results suggest that the relative risk of mutation carriers in the population may be lower than currently believed and that different mutations on the CDKN2A gene may confer substantially different risks of melanoma.

Aged↗
PubMed2005

Etiologic factors associated with p53 immunostaining in cutaneousmalignant melanoma.

Findings from a case-control study of cutaneous malignant melanoma (CMM) in Queensland, Australia, suggest that melanomas exhibiting p53 immunostaining possess different risk factors from those of other melanomas. To further explore this hypothesis, a case-only analysis of risk factors for p53 immunostaining with anti-p53 MAb DO-7 was undertaken in 523 people diagnosed with CMM in Canada and Australia. Phenotypic factors and past sun exposure were measured using a self-administered questionnaire and telephone interview. The presence of strong p53 staining (>10% of cell nuclei positively stained vs. <1% staining) was positively associated with some indicators of high cumulative sun exposure: lentigo maligna melanoma subtype (OR = 3.2 vs. superficial spreading subtype), melanoma location on the head and neck (OR = 2.8 vs. back), histopathologic evidence of solar elastosis (OR = 2.1) and previous diagnosis of nonmelanoma skin cancer (OR = 2.4). Strong staining was negatively associated with high nevus density on the back (OR = 0.2 for >25 nevi vs. 0-3 nevi) and histologic evidence of a coexisting nevus (OR = 0.3). Other factors associated with strong p53 immunostaining include greater Breslow thickness (OR = 7.4 for >4.00 vs. <0.76 mm), male sex (OR = 2.2) and dense freckling (OR = 6.6 vs. few freckles). Of these, thickness, male sex, dense freckling, low nevus density on the back, histologic subtype and history of nonmelanoma skin cancer appeared to be independently associated with strong p53 staining. Our findings are consistent with the Queensland study in suggesting that variables indicating high accumulated sun exposure are positively associated with p53 staining and that an increased number of nevi is positively associated with its absence; they may reflect etiologic and pathogenetic heterogeneity in melanoma.

Adult↗
PubMed2005

Polymorphisms in nucleotide excision repair genes and risk of multiple primary melanoma: the Genes Environment and Melanoma Study.

Polymorphisms in six genes involved in nucleotide excision repair of DNA were examined in a large population-based case-control study of melanoma. Genotyping was conducted for 2485 patients with a single primary melanoma (controls) and 1238 patients with second or higher order primary melanomas (cases). Patients were ascertained from nine geographic regions in Australia, Canada, Italy and the United States. Positive associations were observed for XPD 312 Asn/Asn versus Asp/Asp [odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.2-1.9] and XPD 751 Gln/Gln versus Lys/Lys (OR = 1.4, 95% CI 1.1-1.7) genotypes and melanoma. The combined XPD Asn (A) 312 + Gln (C) 751 haplotype was significantly more frequent in cases (32%) compared with controls (29%) (P = 0.003) and risk of melanoma increased significantly with one and two copies of the haplotype (ORs 1.2, 95% CI 1.0-1.4, and 1.6, 95% CI 1.2-2.0, trend P = 0.002). No significant associations were observed for HR23B codon 249, XPG codon 1104, XPC codon 939, XPF codon 415, XPF nt 2063, ERCC6 codon 1213 or ERCC6 codon 1230. ORs for XPD and XPC genotypes were stronger for melanoma diagnosed at an early age, but tests for interaction were not statistically significant. The results provide further evidence for a role of XPD in the etiology of melanoma.

Adolescent↗
PubMed2005

Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample.

BACKGROUND: Germline mutations in the CDKN2A gene have been linked to melanoma incidence in many families with multiple cases of the disease. Previous studies of multiple-case families have indicated that the lifetime risk (i.e., penetrance) of melanoma in CDKN2A mutation carriers is very high, ranging from 58% in Europe to 91% in Australia by age 80 years. In this study, we examined lifetime melanoma risk among CDKN2A mutation carriers using carriers who were identified in a population-based study of melanoma. METHODS: Probands for the study were incident case patients with either first or subsequent melanoma who were identified in nine geographic regions in Australia, Canada, the United States, and Italy. A total of 3626 probands (53% participation rate) with adequate DNA for analysis were recruited and genotyped for CDKN2A mutations. From the 3550 probands whose DNA could be amplified by polymerase chain reaction of CDKN2A exons 1alpha, 2, and 3 and surrounding regions, 65 mutation carriers were identified. Melanoma histories in first-degree relatives of these probands were used to calculate the lifetime risk in CDKN2A mutation carriers using the kin-cohort method. RESULTS: The risk of melanoma in CDKN2A mutation carriers was approximately 14% (95% CI = 8% to 22%) by age 50 years, 24% (95% CI = 15% to 34%) by age 70 years, and 28% (95% CI = 18% to 40%) by age 80 years. Eighteen probands had three or more first-degree relatives with melanoma, but only one was a carrier of a CDKN2A mutation. CONCLUSIONS: CDKN2A mutation carriers in the general population have a much lower risk of melanoma than that suggested by estimates obtained from multiple-case families. The preponderance of familial clustering of melanoma occurs in families without identifiable mutations in CDKN2A.

Adult↗
PubMed2005

Predictors of self-reported confidence ratings for adult recall of early life sun exposure.

Use of self-reported confidence ratings may be an efficient method for assessing recall bias. In this exploratory application of the method, the authors examined the relation between case-control status and self-reported confidence ratings. In 2002 and 2003, melanoma cases (n = 141) and controls (n = 143) aged 20-44 years residing in Ontario, Canada, estimated the amounts of time they had spent outdoors in summer activities when they were 6-18 years of age and indicated their confidence in the accuracy of each estimate. The generalized estimating equations extension of logistic regression was used to examine dichotomized confidence ratings (more confident vs. less confident) for activities reported for ages 6-11 years and 12-18 years. Types of activity were associated with more confident reporting for both age strata; as the number of stable outdoor activity periods (total number of similar outdoor periods within each activity) reported by respondents increased, confidence decreased. Cumulative time spent outdoors was also associated with more confidence but reached statistical significance only for the age stratum 12-18 years. There was no statistically significant association between case-control status and self-reported confidence for either age stratum (6-11 years: odds ratio = 0.91; 12-18 years: odds ratio = 1.32), which suggests an absence of recall bias for reported time spent outdoors.

Adolescent↗
PubMed2005

Etiologic and other factors predicting nevus-associated cutaneous malignant melanoma.

Cutaneous malignant melanomas with histologic evidence of an associated nevus (N+) may have a different risk factor profile from that of melanomas without it (N-). To address this question, a case-only analysis of 932 people with cutaneous malignant melanoma was done to identify etiologic and other factors associated with N+ melanoma. Evidence of an associated nevus was found in 36% of melanomas. N+ melanomas were thinner (Ptrend=0.0009) and more likely to be of the superficial spreading type than other types of melanoma. Subjects with N+ melanomas were younger (Ptrend<0.0001) and reported a higher nevus density on their skin than subjects with N- melanomas [odds ratio (OR), 3.1; 95% confidence interval (CI), 1.6-6.0, for high nevus density versus no nevi]. Indicators of high accumulated sun exposure were less prevalent among subjects with N+ melanomas (OR, 0.3; 95% CI, 0.2-0.4, for melanoma location on the head and neck versus location on trunk; OR, 0.2; 95% CI, 0.1-0.4, for severe solar elastosis adjacent to the melanoma versus no elastosis; OR, 0.2; 95% CI, 0.1-0.4, for lentigo maligna melanoma subtype versus superficial spreading subtype). With the exception of solar elastosis and age, all of the aforementioned variables remained significantly associated with N+ melanomas in multivariate analyses. No associations with self-reported measures of sun exposure, sunburn, or pigmentation phenotype were apparent. Our findings provide some support for the hypothesis of etiologically separate pathways for melanoma, with N+ melanomas appearing less likely to develop in the presence of characteristics suggesting high accumulated sun exposure than N- melanomas. However, it is possible that high UV exposure causes involution of nevi, thus reducing the density of nevi in exposed skin and thereby the probability of N+ melanoma.

Adult↗
PubMed2004

Familial aggregation of melanoma risks in a large population-based sample of melanoma cases.

OBJECTIVE: Melanoma has been shown in numerous studies to be associated with sun exposure, and with host phenotypic factors of genetic origin. In this study we use information from a large series of incident cases of melanoma from an international population-based study to examine the patterns of incidence of melanoma in the first-degree relatives of these cases. METHODS: A total of 2508 incident cases of melanoma provided information on basic demographic data and pigmentary characteristics, in addition to detailed information on family history of melanoma. These data were used to examine the incidence rates ratios of melanoma in the relatives of cases in relation to population rates, and also with respect to phenotypic characteristics of the probands that have been shown to be associated with melanoma: mole counts, hair color, eye color, and skin sensitivity to the sun. RESULTS: The incidence rates reflect the underlying patterns of incidence in the source populations, with generally higher rates in the Australian sample, low rates in Italy, and intermediate rates in the USA and Canada. Also, rates are higher in men than in women, except at very young ages. Phenotypic characteristics of the probands were only weakly associated with the observed rates in the relatives although there is a strong inverse association with age at diagnosis. Cumulative risk of melanoma rises to 6.9% (6.1%) at age 80 in male (female) first-degree relatives of cases, and to 10.8% (9.5%) in relatives of cases diagnosed before age 50. CONCLUSIONS: Relatives of cases diagnosed with melanoma are at considerable lifetime risk of the disease, especially if the case is diagnosed at a young age.

Adult↗
PubMed2003

Cancer incidence and mortality in Ontario First Nations, 1968-1991 (Canada).

OBJECTIVE: To determine cancer incidence and mortality rates in Ontario First Nations (FN) people (native Indians) during 1968-1991 and to compare these with rates in the Ontario population. METHODS: A cohort of 141,290 Ontario FN was created from registration files maintained by the Canadian government. Cancers and deaths were ascertained by linkage to the provincial cancer registry and mortality file, which also provided general population comparison data. RESULTS: Cancer incidence was significantly lower in FN compared to the general population for all cancer (rate ratio (RR) = 0.72 for females; 0.62 for males), breast cancer (RR = 0.54), lung cancer in men (RR = 0.68), prostate cancer (RR = 0.57) and colorectal cancer (RR = 0.58 and 0.57 in men and women, respectively). Rates were significantly higher in FN for cervical cancer (RR = 1.73) and gallbladder cancer (2.05 and 2.20 in men and women, respectively). Incidence rates increased significantly in FN people between 1968-1975 and 1984-1991 for all cancer and for the major cancers (breast, lung, prostate and colorectal). Colorectal cancer rate ratios were significantly higher in 1984-1991 than in 1968-1975, indicating converging incidence rates. Patterns of cancer mortality were similar. CONCLUSIONS: These trends are compatible with a population in epidemiologic transition to the Euro-American disease pattern which is dominated by chronic diseases.

Adolescent↗
PubMed2003

Workshop report: environmental exposures and cancer prevention.

The Workshop on Environmental Exposures and Cancer was held by Cancer Care Ontario (CCO) 25-26 April 2001. An expert panel convened to achieve consensus on a list of important environmental exposures, priority environmental exposures in Ontario, and recommendations for CCO in the areas of surveillance, research, and prevention activities to address these environmental exposures. Panel members developed a working definition of environmental exposure and criteria to prioritize the identified exposures. The process followed in the workshop provided CCO with important direction for its surveillance, research, and prevention activities to address environmental exposures and cancer. It is hoped that the environmental exposures and the opportunities identified through this workshop process will guide policy makers, program personnel, and researchers interested in and struggling with the challenges associated with surveillance, research, and prevention of environmental exposures.

Environmental Exposure↗
PubMed2002

A proposal for cervical screening information systems in developing countries.

The effective and efficient delivery of cervical screening programs requires information for planning, management, delivery and evaluation. Specially designed systems are generally required to meet these needs. In many developing countries, lack of information systems constitutes an important barrier to development of comprehensive screening programs and the effective control of cervical cancer. Our report outlines a framework for creating such systems in developing countries and describes a conceptual model for a cervical screening information system. The proposed system is modular, recognizing that there will be considerable between-region heterogeneity in current status and priorities. The proposed system is centered on modules that would allow for the assembly and computerization of data on Pap tests, since these represent the main screening modality at the present time. Additional modules would process data and create and maintain a screening database (e.g., standardize, edit, link and update modules) and allow for the integration of other types of data, such as cervical histopathology results. An open systems development model is proposed, since it is most compatible with the goals of local stakeholder involvement and capacity-building.

Databases as Topic↗
PubMed2002

Evaluation of a risk factor survey with three assessment methods.

This paper describes the evaluation of questions on a cancer risk factor survey using three different methods: dataset response patterns, qualitative feedback, and questionnaire appraisal. These methods addressed the survey data, procedures and questions. The three methods identified similar issues but also made unique contributions. Dataset response patterns showed missing and out-of-range data, an order effect, and mixed coding. Qualitative feedback revealed lack of clarity, sensitive topics, technical or undefined terms, failure to hear all response options, overlapping response options (as perceived by respondents), coding problems and recall difficulties. Questionnaire appraisal showed technical or undefined terms, complex syntax, hidden definitions, and ambiguous wording. The survey assessment methods described here can improve data quality, especially when limited time and resources preclude in-depth questionnaire development.

Data Collection↗