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Biomedical subjects

Bruce K Armstrong

Publications and source records attributed to Bruce K Armstrong.

At least 19 recordsLinked to original sources
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

Physical activity and endometrial cancer risk: a review of the current evidence, biologic mechanisms and the quality of physical activity assessment methods.

OBJECTIVES: To (1) determine the nature of the association between physical activity and endometrial cancer risk; (2) assess the contribution of variation in the quality of physical activity measurement to inconsistencies in study results; and (3) review the biologic mechanisms that might mediate possible effects of physical activity on risk. METHODS: We reviewed and summarized all published epidemiologic studies examining physical activity and endometrial cancer risk, and evidence relating to possible biologic mechanisms. We assigned each study a quality score for physical activity measurement. RESULTS: Fourteen of the 18 studies showed a convincing or possible protective effect of physical activity on endometrial cancer risk, with an average relative risk reduction of around 30%. A dose-response relation was observed in 7 of 13 studies. The quality score was not related to the observed strength of association or the presence of a dose-response relation. There was epidemiologic and biologic evidence that vigorous activity, as well as light and moderate intensity activities, such as housework, gardening or walking for transportation, may reduce risk. CONCLUSIONS: Physical activity probably has a protective role in endometrial cancer development. More epidemiologic and biologic evidence is needed to make conclusive recommendations on optimal types, characteristics or time periods of physical activity.

Endometrial Neoplasms↗
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

Polymorphisms in immune function genes and risk of non-Hodgkin lymphoma: findings from the New South Wales non-Hodgkin Lymphoma Study.

Recent findings suggest that genetic polymorphisms in TNF and IL10 are associated with an increased risk of non-Hodgkin lymphoma (NHL), particularly for diffuse large B-cell lymphoma (DLBCL). To further investigate the contribution of common genetic variation in key cytokine and innate immunity genes to the etiology of NHL, we genotyped participants in a case-control study of NHL conducted in Australia (545 cases, 498 controls). We investigated 36 single nucleotide polymorphisms in IL10, TNF and 21 other immune function genes. We observed an elevated risk of DLBCL with the IL10 -3575T>A polymorphism [TA genotype: odds ratio (OR)=1.32, 95% confidence interval (CI)=0.86-2.02; AA, OR=1.84, 95% CI=1.10-3.08; trend test, P=0.02]. Our most noteworthy TNF finding was an association between -857C>T and a decreased risk of NHL (CT or TT, OR=0.59, 95% CI=0.42-0.84, P=0.003) and particularly follicular lymphoma (OR=0.40, 95% CI=0.23-0.68, P=0.0009). Additionally, TNF -863C>A was associated with an elevated risk of DLBCL (CA, OR=1.45, 95% CI=0.95-2.21; AA, OR=2.06, 95% CI=0.88-4.83; trend test, P=0.02). Our findings offer further evidence that variation in the IL10 and TNF loci influences NHL risk. Additional studies are needed to clarify the genetic and biologic basis for these relationships.

Adult↗
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

Trends in survival and excess risk of death after diagnosis of cancer in 1980-1996 in New South Wales, Australia.

Survival from almost all cancers has improved during the last 30 years. There is debate over the reasons for the improvement. We examined trends in survival for 28 cancers from 1980 to 1996 in New South Wales (NSW), Australia, with adjustment for disease spread at diagnosis. NSW Central Cancer Registry data were used to estimate 5-year relative survival and relative excess risk of death for patients diagnosed in 1980-84, 1985-88, 1989-92 and 1993-96. Statistical significance of variation in excess deaths between periods of diagnosis was assessed using Poisson regression, with adjustment for age, sex, duration of follow-up, histology and spread of disease at diagnosis. There were statistically significant falls in excess deaths for 20 of the cancers with a 25% fall for all cancers combined. Cancers of the prostate, liver, thyroid, breast, gallbladder, body of uterus, rectum, cervix and ovary had falls of >30%. The falls varied by spread of disease; the largest being in localised and regionally spread tumours. Overall survival, when unadjusted for spread of cancer, generally fell in parallel with that in the specific categories of spread, which implies that stage migration did not contribute importantly to survival trends. While acknowledging the limitations of incomplete data on stage of cancer at diagnosis, we conclude that falls in excess deaths in NSW from 1980 to 1996 are unlikely, for many cancers, to be attributed to earlier diagnosis or stage migration; thus advances in cancer treatment have almost certainly contributed to them.

Adolescent↗
PubMed2006

Is there a folate-related gene-environment interaction in the etiology of childhood acute lymphoblastic leukemia?

Acute lymphoblastic leukaemia (ALL) is the commonest childhood cancer in developed countries. Little is known about its causes, although its early age at diagnosis has focused interest on maternal and perinatal factors. We have previously observed a protective effect of maternal folate supplementation during pregnancy against ALL, and a number of studies have reported protective effects of some common polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene. One study has suggested that the effect of MTHFR polymorphisms on risk of ALL may depend on folate status. This study aimed to look for evidence of an interaction between maternal folate supplementation and child's genotype among the cases from our previous study. Bone marrow specimens from 82 of 83 case children were available. DNA was extracted and genotyped for MTHFR C677T and A1298C using standard techniques. We used a case-only analysis to estimate the case-only odds ratio (COR) for MTHFR genotype and folate supplementation in association with ALL. None of the CORs indicated a significant departure from a multiplicative model. Adjustment for sex, age or genotype at the other locus had little effect on the results. Other studies of this gene and environment interaction in ALL and other cancers have produced contradictory results, perhaps because of varying definitions of folate exposure. Further research into the interaction of folate intake and genotype in causing ALL and other cancers is needed. We are specifically studying it in an Australian national case-control study of genetic and environmental causes of ALL.

Alanine↗
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

Pregnancy history and incidence of melanoma in women: a pooled analysis.

There is evidence that pregnancy history including age at first birth and parity may play a role in risk of cutaneous melanoma in women, although, epidemiological findings are inconsistent. We conducted a collaborative analysis of these factors using the original data from ten completed case-control studies (2391 cases and 3199 controls), and assessed the potential confounding effects of socioeconomic, pigmentary, and sun exposure-related factors. We found no overall association with ever having a live birth (pooled odds ratio (pOR) 0.95, 95% confidence interval (CI) 0.67-1.35). However, we detected a reduced risk of melanoma among women with higher parity (> or = 5 versus no live births pOR 0.76, 95% CI 0.49-1.18, each live birth pOR 0.95, 95% CI 0.91-0.99, p trend = 0.05). Women with both earlier age at first birth (e.g., <20 years) and higher parity (e.g., > or = 5 live births) had a particularly lower risk than women with later age at first birth (e.g., > or = 25 years) and lower parity (e.g., <5 live births) (pOR 0.33, 95% CI 0.14-0.75). The results are compatible with an effect of reproductive history-related factors on melanoma risk, but also could reflect differences in other factors, such as sun exposure history.

Adult↗
PubMed2006

Variation in incidence and fatality of melanoma by season of diagnosis in new South Wales, Australia.

Seasonal variation in cutaneous melanoma incidence with a summer peak is poorly understood. It has been hypothesized to be due to increased diagnosis in summer or a late-promoting effect of sun exposure. We analyzed the characteristics of incident cases of cutaneous melanoma and their outcome by season of diagnosis in the population of New South Wales, Australia. Cases of melanoma (25,845 cases; 10,869 females and 14,976 males) were registered by the New South Wales Central Cancer Registry in 1989 to 1998. There was significant seasonal variation in incidence (P < 0.0001, Nam test). The summer to winter ratio was greater for women, younger people, lesions on the limbs, and superficial spreading melanoma. Melanomas were thicker in winter than in summer (medians 0.75 and 0.70 mm, respectively; P < 0.0001, Kruskal-Wallis test). Cases were followed for a median of 63 months and 2,710 (10.5%) died from their melanoma. Fatality from melanoma was lower for melanomas diagnosed in summer than winter (relative fatality = 0.72; 95% confidence interval, 0.65-0.81); the 5-year survival rate was 92.1% for diagnosis in summer and 89.0% for diagnosis in winter. This result remained significant after adjustment for year of diagnosis, age, sex, Breslow thickness, anatomic location, and histologic type (relative fatality = 0.82; 95% confidence interval, 0.72-0.94). Seasonality in melanoma incidence is probably caused mainly by increased and earlier diagnosis in summer, although a late-stage promotional effect of sun exposure cannot be excluded completely. Earlier diagnosis may also reduce fatality when melanoma is diagnosed in summer. Independence of variation in fatality with season from seasonal variation in thickness, however, suggests that sun exposure around the time of diagnosis decreases fatality of melanoma.

Adult↗
PubMed2006

Buccal DNA collection: comparison of buccal swabs with FTA cards.

Collection and analysis of DNA, most commonly from blood or buccal cells, is becoming more common in epidemiologic studies. Buccal samples, which are painless to take and relatively easily collected, are often the preferred source. There are several buccal cell collection methods: swabs, brushes, mouthwash, and treated cards, such as FTA or IsoCode cards. Few studies have systematically compared methods of buccal cell collection with respect to DNA yield and amplification success under similar conditions. We compared buccal DNA collection and amplification using buccal swabs and FTA cards in 122 control subjects from our Australian case-control study of childhood acute lymphoblastic leukaemia. Buccal DNA was quantified using a real-time PCR for beta-actin and genotyped at the loci of three polymorphisms (MTHFR 677C>T, ACE I/D, and XPD 1012G>A). PCR was successful with DNA from buccal swabs for 62% to 89% of subjects and from FTA cards for 83% to 100% of subjects, depending on the locus. The matched pair odds ratios (95% confidence interval) comparing success of FTA cards with buccal swabs are as follows: MTHFR 677C>T using PCR-RFLP, 12.5 (11.6-13.5) and using real-time PCR, 130.0 (113.1-152.8); ACE I/D using PCR-amplified fragment length polymorphism, 3.36 (3.2-3.5); XPD 1012G>A using real-time PCR, 150.0 (132.7-172.3). FTA cards are a robust DNA collection method and generally produce DNA suitable for PCR more reliably than buccal swabs. There are, however, technical challenges in handling discs punched from FTA cards that intending users should be aware of.

Cheek↗
PubMed2006

Specific infections, infection-related behavior, and risk of non-Hodgkin lymphoma in adults.

Infections were examined as possible risk factors for non-Hodgkin lymphoma in a population-based case-control study in New South Wales and the Australian Capital Territory, Australia. Incident cases (n = 694) had no history of HIV infection or transplantation. Controls (n = 694) were randomly selected from electoral rolls and frequency matched to cases by age, sex, and area of residence. A postal questionnaire and telephone interview measured history of specific infections, occupational exposures, and behavioral and other risk factors for infection. Blood samples were tested for antibodies to human T-lymphotrophic virus type I and hepatitis C virus. Logistic regression models included the three matching variables and ethnicity. There was no association between risk of non-Hodgkin lymphoma and any of the variables analyzed, including sexually transmitted infections, sexual behavior, blood transfusions, influenza, acne, and either occupational or domestic exposure to zoonotic infections. Non-Hodgkin lymphoma risk was nonsignificantly elevated (odds ratio, 2.99; 95% confidence interval, 0.78-11.51) for those with a history of injecting drug use. Three cases and two controls (odds ratio, 1.32; 95% confidence interval, 0.22-7.98) tested positive to hepatitis C virus infection and none tested positive to human T-lymphotrophic virus type I/II infection. This study provides consistent evidence that sexually transmitted infections and zoonoses are not risk factors for non-Hodgkin lymphoma.

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

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

A population-based study from New South Wales, Australia 1996-2001: area variation in survival from colorectal cancer.

In this study, we have investigated the impact of area of residence on survival from colon and rectal cancer. Relative survival and relative excess risk of death from cancer were calculated for each of 17 health areas in New South Wales, Australia. There were statistically significant differences in survival across areas for both cancers after adjusting for demographic factors. The variation remained for colon cancer but was reduced for rectal cancer after adjustment for spread of disease at diagnosis. This persistent variation in colon cancer survival suggests that variation in treatment contributes to it, and there is separate evidence for such variation. Of the 7186 patients whose deaths within five years were attributable to colorectal cancer, 784 could have had their survival increased to more than five years if the excess risk of death in all areas was reduced to the 20th centile of its distribution. Estimates such as this can assist in prioritizing improvements in cancer services.

Adolescent↗
PubMed2005

Lung cancer rate predictions using generalized additive models.

Predictions of lung cancer incidence and mortality are necessary for planning public health programs and clinical services. It is proposed that generalized additive models (GAMs) are practical for cancer rate prediction. Smooth equivalents for classical age-period, age-cohort, and age-period-cohort models are available using one-dimensional smoothing splines. We also propose using two-dimensional smoothing splines for age and period. Variance estimation can be based on the bootstrap. To assess predictive performance, we compared the models with a Bayesian age-period-cohort model. Model comparison used cross-validation and measures of predictive performance for recent predictions. The models were applied to data from the World Health Organization Mortality Database for females in five countries. Model choice between the age-period-cohort models and the two-dimensional models was equivocal with respect to cross-validation, while the two-dimensional GAMs had very good predictive performance. The Bayesian model performed poorly due to imprecise predictions and the assumption of linearity outside of observed data. In summary, the two-dimensional GAM performed well. The GAMs make the important prediction that female lung cancer rates in these countries will be stable or begin to decline in the future.

Adult↗