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The objective of this study was to evaluate a clinic-centered oral cancer screening initiative in one of the poorest communities in Canada, assessing the need for screening and the acceptance of screening and identifying hindrances to both screening and follow-up. The study group included 204 people in the Vancouver Downtown Eastside (DTES). This was shown to be a high-risk community based on risk factors, lack of access to care, and the high frequency of oral mucosal anomalies. Acceptance of screening was high (98%); however, acceptance of biopsy for abnormal findings and follow-up was low. Among the 12 patients with clinical leukoplakia who were biopsied, 10 showed cancer or precancer. In summary, these data show a need for screening in this population and an ability to recruit patients to screening. They support a future expansion of this initiative to create a more comprehensive strategy for outreach to this underserved community that extends to screening, diagnostic work-up, and treatment. [ABSTRACT FROM AUTHOR]

The objective of the study was to develop a culturally relevant video and a pamphlet for use as a cervical cancer screening educational intervention among North-American Chinese women. The project conducted 87 qualitative interviews and nine focus groups to develop a culturally tailored intervention to improve Pap testing rates. The intervention consisted of an educational/motivational video, a pamphlet, and home visits. Less acculturated Chinese women draw on a rich tradition of herbal knowledge and folk practices historically based on Chinese medical theory, now mixed with new information from the media and popular culture. The video, the pamphlet, and the outreach workers knowledge base were designed using these results and combined with biomedical information to address potential obstacles to Pap testing. Culturally relevant information for reproductive health promotion was easily retrieved through qualitative interviews and used to create educational materials modeling the integration of Pap testing into Chinese women's health practices. [ABSTRACT FROM AUTHOR]

The article focuses on skin lesions characteristic of pseudoxanthoma elasticum. Despite the characteristic appearance of the affected areas of skin, pseudoxanthoma elasticum unrelated to the true xanthomatoses, being rather a diffuse degenerative process with both visceral and cutaneous manifestations, characterized by the local accumulation of abnormal protein with many of the histochemical reactions of elastic tissue. Pseudoxanthoma elasticum is probably of genetic origin and may be inherited as an autosomal recessive with partial limitation to the female.

Background: Extensive mammographic density is associated with an increased risk of breast cancer and makes the detection of cancer by mammography difficult, but the influence of density on risk according to method of cancer detection is unknown. Methods: We carried out three nested case-control studies in screened populations with 1112 matched case-control pairs. We examined the association of the measured percentage of density in the baseline mammogram with risk of breast cancer, according to method of cancer detection, time since the initiation of screening, and age. Results: As compared with women with density in less than 10% of the mammogram, women with density in 75% or more had an increased risk of breast cancer (odds ratio, 4.7; 95% confidence interval [CI], 3.0 to 7.4), whether detected by screening (odds ratio, 3.5; 95% CI, 2.0 to 6.2) or less than 12 months after a negative screening examination (odds ratio, 17.8; 95% CI, 4.8 to 65.9). Increased risk of breast cancer, whether detected by screening or other means, persisted for at least 8 years after study entry and was greater in younger than in older women. For women younger than the median age of 56 years, 26% of all breast cancers and 50% of cancers detected less than 12 months after a negative screening test were attributable to density in 50% or more of the mammogram. Conclusions: Extensive mammographic density is strongly associated with the risk of breast cancer detected by screening or between screening tests. A substantial fraction of breast cancers can be attributed to this risk factor. [ABSTRACT FROM AUTHOR]

Background: Our purpose is to develop a testable biological hypothesis to explain the known increased risk of breast cancer associated with extensive percent mammographic density (PMD), and to reconcile the apparent paradox that although PMD decreases with increasing age, breast cancer incidence increases., Methods: We used the Moolgavkar model of carcinogenesis as a framework to examine the known biological properties of the breast tissue components associated with PMD that includes epithelium and stroma, in relation to the development of breast cancer. In this model, normal epithelial cells undergo a mutation to become intermediate cells, which, after further mutation, become malignant cells. A clone of such cells grows to become a tumor. The model also incorporates changes with age in the number of susceptible epithelial cells associated with menarche, parity, and menopause. We used measurements of the radiological properties of breast tissue in 4454 healthy subjects aged from 15 to 80+ years to estimate cumulative exposure to PMD (CBD) in the population, and we examined the association of CBD with the age-incidence curve of breast cancer in the population., Results: Extensive PMD is associated with a greater number of breast epithelial cells, lobules, and fibroblasts, and greater amounts of collagen and extracellular matrix. The known biological properties of these tissue components may, singly or in combination, promote the acquisition of mutations by breast epithelial cells specified by the Moolgavkar model, and the subsequent growth of a clone of malignant cells to form a tumor. We also show that estimated CBD in the population from ages 15 to 80+ years is closely associated with the age-incidence curve of breast cancer in the population., Conclusions: These findings are consistent with the hypothesis that the biological properties of the breast tissue components associated with PMD increase the probability of the transition of normal epithelium to malignant cells, and that the accumulation of mutations with CBD may influence the age-incidence curve of breast cancer. This hypothesis gives rise to several testable predictions.

Background: Many factors contribute to socioeconomic status (SES), yet in most survival studies only income is used as a measure for determining SES. We used a complex, composite, census-based metric for socioeconomic deprivation to better distinguish individuals with lower SES and assess its impact on survival and staging trends of oral cancers., Methods: Oropharyngeal (OPC) and oral cavity cancer (OCC) cases were identified from the British Columbia cancer registry between 1981-2009 and placed into affluent and deprived neighborhoods using postal codes linked to VANDIX (a composite SES index based on 7 census variables encompassing income, housing, family structure, education, and employment). Stage and cancer-specific survival rates were examined by sex, SES, and time period., Results: Approximately 50 % of OPC and OCC cases of both sexes resided in SES deprived neighborhoods. Numbers of cases have increased in recent years for all but OCC in men. The deprivation gap in survival between affluent and deprived neighborhoods widened in recent years for OPC and OCC in men, while decreasing for OPC and increasing slightly for OCC in women. Greater proportions of OCC cases were diagnosed at later stage disease for both sexes residing in deprived neighborhoods, a trend not seen for OPC., Conclusion: SES remains a significant independent determinant of survival for both OPC and OCC when using a composite metric for SES. OPC survival rates among men have improved, albeit at slower rates in deprived communities. OCC screening programs need to be targeted towards SES-deprived neighborhoods where greater proportions of cases were diagnosed at a later stage and survival rates have significantly worsened in both sexes.

Objectives: The sensitivity of screening mammography is much lower among women who have dense breast tissue, compared with women who have largely fatty breasts, and they are also at much higher risk of developing the disease. Increasing mammography screening frequency from biennially to annually has been suggested as a policy option to address the elevated risk in this population. The purpose of this study was to assess the cost-effectiveness of annual versus biennial screening mammography among women aged 50-79 with dense breast tissue., Methods: A Markov model was constructed based on screening, diagnostic, and treatment pathways for the population-based screening and cancer care programme in British Columbia, Canada. Model probabilities and screening costs were calculated from screening programme data. Costs for breast cancer treatment were calculated from treatment data, and utility values were obtained from the literature. Incremental cost-effectiveness was expressed as cost per quality adjusted life year (QALY), and probabilistic sensitivity analysis was conducted., Results: Compared with biennial screening, annual screening generated an additional 0.0014 QALYs (95% CI: -0.0480-0.0359) at a cost of $819 ($ = Canadian dollars) per patient (95% CI: 506-1185), resulting in an incremental cost effectiveness ratio of $565,912/QALY. Annual screening had a 37.5% probability of being cost-effective at a willingness-to-pay threshold of $100,000/QALY., Conclusion: There is considerable uncertainty about the incremental cost-effectiveness of annual mammography. Further research on the comparative effectiveness of screening strategies for women with high mammographic breast density is warranted, particularly as digital mammography and density measurement become more widespread, before cost-effectiveness can be reevaluated., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Introduction: Percent mammographic density (PMD) is associated with an increased risk of interval breast cancer in screening programs, as are younger age, pre-menopausal status, lower body mass index and hormone therapy. These factors are also associated with variations in PMD. We have examined whether these variables influence the relative frequency of interval and screen-detected breast cancer, independently or through their associations with PMD. We also examined the association of tumor size with PMD and dense and non-dense areas in screen-detected and interval breast cancers., Methods: We used data from three case-control studies nested in screened populations. Interval breast cancer was defined as invasive breast cancer detected within 12 months of a negative mammogram. We used a computer-assisted method of measuring the dense and total areas of breast tissue in the first (baseline) mammogram taken at entry to screening programs and calculated the non-dense area and PMD. We compared these mammographic features, and other risk factors at baseline, in women with screen-detected (n = 718) and interval breast cancer (n = 125)., Results: In multi-variable analysis, the baseline characteristics of younger age, greater dense area and smaller non-dense mammographic area were significantly associated with interval breast cancer compared to screen-detected breast cancer. Compared to screen-detected breast cancers, interval cancers had a larger maximum tumor diameter within each mammographic measure., Conclusions: Age and the dense and non-dense areas in the baseline mammogram were independently associated with interval breast cancers in screening programs. These results suggest that decreased detection of cancers caused by the area of dense tissue, and more rapid growth associated with a smaller non-dense area, may both contribute to risk of interval breast cancer. Tailoring screening to individual mammographic characteristics at baseline may reduce the number of interval cancers.

Background: Fibroglandular breast tissue appears dense on mammogram, whereas fat appears nondense. It is unclear whether absolute or percentage dense area more strongly predicts breast cancer risk and whether absolute nondense area is independently associated with risk., Methods: We conducted a meta-analysis of 13 case-control studies providing results from logistic regressions for associations between one standard deviation (SD) increments in mammographic density phenotypes and breast cancer risk. We used random-effects models to calculate pooled odds ratios and 95% confidence intervals (CIs). All tests were two-sided with P less than .05 considered to be statistically significant., Results: Among premenopausal women (n = 1776 case patients; n = 2834 control subjects), summary odds ratios were 1.37 (95% CI = 1.29 to 1.47) for absolute dense area, 0.78 (95% CI = 0.71 to 0.86) for absolute nondense area, and 1.52 (95% CI = 1.39 to 1.66) for percentage dense area when pooling estimates adjusted for age, body mass index, and parity. Corresponding odds ratios among postmenopausal women (n = 6643 case patients; n = 11187 control subjects) were 1.38 (95% CI = 1.31 to 1.44), 0.79 (95% CI = 0.73 to 0.85), and 1.53 (95% CI = 1.44 to 1.64). After additional adjustment for absolute dense area, associations between absolute nondense area and breast cancer became attenuated or null in several studies and summary odds ratios became 0.82 (95% CI = 0.71 to 0.94; P heterogeneity = .02) for premenopausal and 0.85 (95% CI = 0.75 to 0.96; P heterogeneity < .01) for postmenopausal women., Conclusions: The results suggest that percentage dense area is a stronger breast cancer risk factor than absolute dense area. Absolute nondense area was inversely associated with breast cancer risk, but it is unclear whether the association is independent of absolute dense area., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Oral cancer is an important health issue, with changing incidence in many countries. Oropharyngeal cancer (OPC, in tonsil and oropharygeal areas) is increasing, while oral cavity cancer (OCC, other sites in the mouth) is decreasing. There is the need to identify high risk groups and communities for further study and intervention. The objective of this study was to determine how the incidence of OPC and OCC varied by neighbourhood socioeconomic status (SES) in British Columbia (BC), including the magnitude of any inequalities and temporal trends., Methods: ICDO-3 codes were used to identify OPC and OCC cases in the BC Cancer Registry from 1981-2010. Cases were categorized by postal codes into SES quintiles (q1-q5) using VANDIX, which is a census-based, multivariate weighted index based on neighbourhood average household income, housing tenure, educational attainment, employment and family structure. Age-standardized incidence rates were determined for OPC and OCC by sex and SES quintiles and temporal trends were then examined., Results: Incidence rates are increasing in both men and women for OPC, and decreasing in men and increasing in women for OCC. This change is not linear or proportionate between different SES quintiles, for there is a sharp and dramatic increase in incidence according to the deprivation status of the neighbourhood. The highest incidence rates in men for both OPC and OCC were observed in the most deprived SES quintile (q5), at 1.7 times and 2.2 times higher, respectively, than men in the least deprived quintile (q1). For OPC, the age-adjusted incidence rates significantly increased in all SES quintiles with the highest increase observed in the most deprived quintile (q5). Likewise, the highest incidence rates for both OPC and OCC in women were observed in the most deprived SES quintile (q5), at 2.1 times and 1.8 times higher, respectively, than women in the least deprived quintile (q1)., Conclusion: We report on SES disparities in oral cancer, emphasizing the need for community-based interventions that address access to medical care and the distribution of educational and health promotion resources among the most SES deprived communities in British Columbia.

Physical activity is recognized as a modifiable lifestyle risk factor that may prevent breast cancer. The aim of this cross-sectional study was to compare the physical activity patterns in two populations with different risks for breast cancer. We collected physical activity information from two groups of postmenopausal Canadian women with substantially different risks of developing breast cancer - Caucasians (N=372) and recent Chinese migrants from urban China (N=352). The frequency, duration, and intensity of occupational, household, and recreational activities were measured throughout the lifetime using the interviewer-administered Lifetime Total Physical Activity Questionnaire. Compared with Caucasians, Chinese migrants reported lower average total physical activity over their lifetime and for each age period (0-21, 21-29, 30-39, 40-49, and ≥ 50 years). Compared with Caucasians, Chinese migrants reported greater lifetime occupational activity, but lower levels of lifetime activity for both household and recreation activity. Among Chinese migrants, reported levels of occupational, household, and recreational activities were all greater in migrants from Mainland China than in migrants from Hong Kong. In conclusion, our results show that total activity was greater amongst Caucasians than Chinese migrants, suggesting that the lower breast cancer risk in urban Chinese women is not likely to be explained by greater total physical activity.

There have been recent reports of a rare variant of renal cell carcinoma associated with upregulation of the anaplastic lymphoma kinase gene (ALK) arising as a consequence of chromosomal translocations. The tumours were described as having a characteristic morphology. Here, we describe a case with similar morphology characterised by eosinophilic cells, abundant intracytoplasmic lumina and scattered large ganglion-like tumour cells. There was focal staining for ALK demonstrated by immunohistochemistry. However, rather than exhibiting a chromosomal translocation involving ALK, the use of FISH and a break-apart probe demonstrated that there was increased copy number of intact 2p23, the chromosomal region containing the ALK gene. Furthermore, the use of comparative genomic hybridisation showed increase of the whole of chromosome 2 along with chromosomes 6 and 17. There was no evidence of loss of 3p nor of trisomy of 7 associated with clear cell and papillary carcinoma, respectively. We suggest that this demonstrates a novel mechanism of upregulation of ALK activity by increased copy number occurring during the development of a renal carcinoma with the characteristic ALK-associated morphology.

The poor survival of adenocarcinomas of the gastroesophageal junction (GEJ) makes them clinically important. Discovery of host genetic factors that affect outcome may guide more individualized treatment. This study tests whether constitutional genetic variants in matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) genes are associated with outcome of GEJ adenocarcinoma. Single nucleotide polymorphisms (SNPs) at four TIMP (TIMP1-4) and three MMP genes (MMP2, MMP7 and MMP9) were genotyped in DNA samples from a prospective cohort of patients with primary adenocarcinoma of the GEJ admitted to the British Columbia Cancer Agency. Cox proportional hazards regression, with adjustment for patient, disease and treatment variables, was used to estimate the association of SNPs with survival. Genotypes for 85 samples and 48 SNPs were analyzed. Four SNPs across TIMP3, (rs130274, rs715572, rs1962223 and rs5754312) were associated with survival. Interaction analyses revealed that the survival associations with rs715572 and rs5754312 are specific and significant for 5FU+cisplatin treated patients. Sanger sequencing of the TIMP3 coding and promoter regions revealed an additional SNP, rs9862, also associated with survival. TIMP3 genetic variants are associated with survival and may be potentially useful in optimizing treatment strategies for individual patients.

Background: Percent mammographic density (PMD) is a strong risk factor for breast cancer that changes in response to changes in hormone exposure. We have examined the magnitude of the association of hormone exposure with PMD according to subsequent breast cancer risk., Methods: In three case-control studies, with 1,164 patient cases and 1,155 controls nested in cohorts of women screened with mammography, we examined the association of PMD measured in the baseline mammogram with risk of breast cancer in the following 1 to 8 years (mean, 3 years), according to use of oral contraceptives (OCs) in premenopausal women, menopause, and hormone therapy (HT) in postmenopausal women. All statistical comparisons are adjusted for age and other risk factors., Results: In premenopausal women who later developed breast cancer (patient cases), PMD was 5.3% greater in past users of OCs than in nonusers (P = .06). In controls, OC users had 2% less density than nonusers (P = .44; test for interaction P = .06). The difference in PMD between premenopausal and postmenopausal women for patient cases was 8.5% (P < .001) and for controls, 3.9% (P = .01; test for interaction P = .03). In postmenopausal women, PMD was 6% greater in patients who used HT than in never users (P < .001). Controls who used HT had 1.6% greater PMD (P = .26) than never users (test for interaction P = .001). Differences in PMD resulted mainly from differences in the dense area of the mammogram., Conclusion: Differences in PMD associated with differences in hormone exposure were greater in women who later developed breast cancer than in controls in each of the hormone exposures examined.

Epidemiologic data and animal experiments suggest that dietary fat may influence risk of breast cancer. To determine whether intervention with a low-fat, high-carbohydrate diet would reduce breast cancer incidence in women at increased risk of the disease, we carried out a randomized controlled trial in Canada. We recruited 4,690 women with extensive mammographic density and randomized them to an intervention group or a comparison group. The intervention group received intensive dietary counseling to reduce fat intake to a target of 15% of calories and increase carbohydrate to 65% of calories. Dietary intakes were assessed throughout using food records. Subjects were followed for at least 7 years and for an average of 10 years. The main outcome was invasive breast cancer. Percentage of calories from fat in the intervention group decreased from 30% at baseline to 20% after randomization and remained 9% to 10% lower than the comparison group throughout. There were 118 invasive breast cancers in the intervention group and 102 in the comparison group [adjusted hazard ratio = 1.19 (95% CI: 0.91-1.55)]. Analysis of food records showed that fat intake at baseline and after randomization was not associated with total breast cancer incidence. Greater weight and lower carbohydrate intake at baseline and after randomization were associated with an increased risk of estrogen receptor (ER)-positive breast cancer. Our findings suggest that a sustained reduction in dietary fat intake did not reduce risk of breast cancer in women with extensive mammographic density. Weight and carbohydrate intakes were associated with risk of ER-positive breast cancer., (© 2011 AACR.)

International differences in breast cancer rates and diet, and studies in migrants, suggest that diet may be a modifiable risk factor for breast cancer. The goal of this cross-sectional study was to examine the dietary intakes of women from populations considered to be at different risks for breast cancer. We collected four 24-h food recalls in 3 groups of postmenopausal Canadian women: Caucasians (n = 392), Chinese women born in the West or who migrated to the West before age 21 (n = 156), and recent Chinese migrants (n = 383). Compared to Caucasians, recent Chinese migrants had lower energy and fat intakes and higher protein and carbohydrate intakes. Recent Chinese migrants consumed higher amounts of grains, vegetables, fish, and soy and lower amounts of alcohol, meat, dairy products, and sweets than Caucasians. Western-born Chinese and early Chinese migrants had intakes intermediate between the other 2 groups. The differences in intake between the ethnic groups suggest foods and nutrients that may contribute to the differences in risk of breast cancer between women in Canada and China. Future work will examine whether these dietary differences are associated with biological markers of breast cancer risk.

The use of comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays has dramatically altered the approach to identification of genetic alterations that can explain intellectual disability and /or congenital anomalies. However, the discovery of numerous copy number changes with benign or unknown clinical significance has made interpretation problematic. Submicroscopic duplication of Xp22.31 has been reported as either a possible cause of intellectual disability and/or developmental delay or a benign variant. Here we report 29 individuals with the microduplication found as part of microarray analysis of 7793 samples submitted to an international group of 13 clinical laboratories. The referral reasons varied and included developmental delay, intellectual disability, autism, dysmorphic features and/or multiple congenital anomalies. The size of the Xp22.31 duplication varied between 149 kb and 1.74 Mb and included the steroid sulfatase (STS) gene with the male to female ratio of 0.7. Duplication within this segment is seen at a frequency of 0.15% in a healthy control population, whereas a frequency of 0.37% was observed in our cohort of individuals with abnormal phenotypes. We present a detailed comparison of the breakpoints, inheritance, X-inactivation and clinical phenotype in our cohort and a review of the literature for a total of 41 patients. To date, this report is the largest compilation of clinical and array data regarding the microduplication of Xp22.31 and will serve to broaden the knowledge of regions involving copy number variation (CNV)., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Introduction: Striking differences exist between countries in the incidence of breast cancer. The causes of these differences are unknown, but because incidence rates change in migrants, they are thought to be due to lifestyle rather than genetic differences. The goal of this cross-sectional study was to examine breast cancer risk factors in populations with different risks for breast cancer., Methods: We compared breast cancer risk factors among three groups of postmenopausal Canadian women at substantially different risk of developing breast cancer - Caucasians (N = 413), Chinese women born in the West or who migrated to the West before age 21 (N = 216), and recent Chinese migrants (N = 421). Information on risk factors and dietary acculturation were collected by telephone interviews using questionnaires, and anthropometric measurements were taken at a home visit., Results: Compared to Caucasians, recent Chinese migrants weighed on average 14 kg less, were 6 cm shorter, had menarche a year later, were more often parous, less often had a family history of breast cancer or a benign breast biopsy, a higher Chinese dietary score, and a lower Western dietary score. For most of these variables, Western born Chinese and early Chinese migrants had values intermediate between those of Caucasians and recent Chinese migrants. We estimated five-year absolute risks for breast cancer using the Gail Model and found that risk estimates in Caucasians would be reduced by only 11% if they had the risk factor profile of recent Chinese migrants for the risk factors in the Gail Model., Conclusions: Our results suggest that in addition to the risk factors in the Gail Model, there likely are other factors that also contribute to the large difference in breast cancer risk between Canada and China.