Search

Contains fulltext : 244113.pdf (Publisher’s version ) (Open Access), PURPOSE: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS(313)) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. METHODS: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS(313) and CBC risk. RESULTS: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS(313) showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS(313), HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS(313) 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. CONCLUSION: The PRS(313) can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS(313) needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.

Contains fulltext : 244113.pdf (Publisher’s version ) (Open Access), PURPOSE: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS(313)) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. METHODS: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS(313) and CBC risk. RESULTS: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS(313) showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS(313), HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS(313) 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. CONCLUSION: The PRS(313) can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS(313) needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.

Contains fulltext : 244113.pdf (Publisher’s version ) (Open Access), PURPOSE: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS(313)) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. METHODS: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS(313) and CBC risk. RESULTS: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS(313) showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS(313), HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS(313) 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. CONCLUSION: The PRS(313) can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS(313) needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.

Item does not contain fulltext, Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G x E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 x 10(-07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15-1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72-1.11, P for interaction = 3.2 x 10(-05)). Our findings confirm comparable power of the recent methods for detecting G x E interaction and the utility of using G x E interaction analyses to identify new susceptibility loci.

Item does not contain fulltext, Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G x E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 x 10(-07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15-1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72-1.11, P for interaction = 3.2 x 10(-05)). Our findings confirm comparable power of the recent methods for detecting G x E interaction and the utility of using G x E interaction analyses to identify new susceptibility loci.

Item does not contain fulltext, Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G x E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 x 10(-07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15-1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72-1.11, P for interaction = 3.2 x 10(-05)). Our findings confirm comparable power of the recent methods for detecting G x E interaction and the utility of using G x E interaction analyses to identify new susceptibility loci.

Item does not contain fulltext, Bij de vormgeving van de pedagogische functie van het onderwijs worden ook aan de schoolleiding speciale verwachtingen gesteld. Zo wordt van de schoolleiding een inspirerende rol op het gebied van waarden en normen verwacht. Meer in het bijzonder wordt van schoolleiders verwacht dat deze ook waarden en normen ‘stimuleren’ en ‘voorleven’. Met name vanuit de (levensbeschouwelijke en/of pedagogische) missie van de instelling wordt in deze vaak een beroep op de schoolleiding gedaan om (de identiteitgerichte) waarden te laten doorklinken in waardegestuurd leidersgedrag en schoolbeleid. In dit rapport wordt verslag gedaan van een onderzoek naar de pedagogische taakaspecten en de morele moed die van schoolleiders gevraagd wordt om hun taak naar behoren uit te voeren. Aanvrager van dit onderzoek is de Protestants Christelijke Vereniging van Personeel werkzaam in het BVE-veld en VO. Achtergrond van het onderzoek is de gedachte dat de persoonlijke, levensbeschouwelijke en professionele waarden van de schoolleider doorwerken in het alledaags handelen en het nemen van beleidsbeslissingen. De onderzochte schoolleiders blijken gericht te zijn op het inrichten van de school als een morele en pedagogische gemeenschap gerelateerd aan het primaire doel van de school als een leergemeenschap. Morele moed heeft volgens hen te maken met het durven aan te spreken van mensen op het gebied van waarden en normen. Een tweede aspect van morele moed betreft de volharding, oftewel het kunnen en willen vasthouden aan een vastgestelde koers. Een derde aspect van morele moed heeft betrekking op het willen zijn van een moreel voorbeeld voor hun personeelsleden, leerlingen en andere betrokkenen. Schoolleiders in dit onderzoek zien het tonen van morele moed als een noodzaak om goed leiding te kunnen geven aan hun onderwijsinstelling.

Item does not contain fulltext, Bij de vormgeving van de pedagogische functie van het onderwijs worden ook aan de schoolleiding speciale verwachtingen gesteld. Zo wordt van de schoolleiding een inspirerende rol op het gebied van waarden en normen verwacht. Meer in het bijzonder wordt van schoolleiders verwacht dat deze ook waarden en normen ‘stimuleren’ en ‘voorleven’. Met name vanuit de (levensbeschouwelijke en/of pedagogische) missie van de instelling wordt in deze vaak een beroep op de schoolleiding gedaan om (de identiteitgerichte) waarden te laten doorklinken in waardegestuurd leidersgedrag en schoolbeleid. In dit rapport wordt verslag gedaan van een onderzoek naar de pedagogische taakaspecten en de morele moed die van schoolleiders gevraagd wordt om hun taak naar behoren uit te voeren. Aanvrager van dit onderzoek is de Protestants Christelijke Vereniging van Personeel werkzaam in het BVE-veld en VO. Achtergrond van het onderzoek is de gedachte dat de persoonlijke, levensbeschouwelijke en professionele waarden van de schoolleider doorwerken in het alledaags handelen en het nemen van beleidsbeslissingen. De onderzochte schoolleiders blijken gericht te zijn op het inrichten van de school als een morele en pedagogische gemeenschap gerelateerd aan het primaire doel van de school als een leergemeenschap. Morele moed heeft volgens hen te maken met het durven aan te spreken van mensen op het gebied van waarden en normen. Een tweede aspect van morele moed betreft de volharding, oftewel het kunnen en willen vasthouden aan een vastgestelde koers. Een derde aspect van morele moed heeft betrekking op het willen zijn van een moreel voorbeeld voor hun personeelsleden, leerlingen en andere betrokkenen. Schoolleiders in dit onderzoek zien het tonen van morele moed als een noodzaak om goed leiding te kunnen geven aan hun onderwijsinstelling.

Item does not contain fulltext, Bij de vormgeving van de pedagogische functie van het onderwijs worden ook aan de schoolleiding speciale verwachtingen gesteld. Zo wordt van de schoolleiding een inspirerende rol op het gebied van waarden en normen verwacht. Meer in het bijzonder wordt van schoolleiders verwacht dat deze ook waarden en normen ‘stimuleren’ en ‘voorleven’. Met name vanuit de (levensbeschouwelijke en/of pedagogische) missie van de instelling wordt in deze vaak een beroep op de schoolleiding gedaan om (de identiteitgerichte) waarden te laten doorklinken in waardegestuurd leidersgedrag en schoolbeleid. In dit rapport wordt verslag gedaan van een onderzoek naar de pedagogische taakaspecten en de morele moed die van schoolleiders gevraagd wordt om hun taak naar behoren uit te voeren. Aanvrager van dit onderzoek is de Protestants Christelijke Vereniging van Personeel werkzaam in het BVE-veld en VO. Achtergrond van het onderzoek is de gedachte dat de persoonlijke, levensbeschouwelijke en professionele waarden van de schoolleider doorwerken in het alledaags handelen en het nemen van beleidsbeslissingen. De onderzochte schoolleiders blijken gericht te zijn op het inrichten van de school als een morele en pedagogische gemeenschap gerelateerd aan het primaire doel van de school als een leergemeenschap. Morele moed heeft volgens hen te maken met het durven aan te spreken van mensen op het gebied van waarden en normen. Een tweede aspect van morele moed betreft de volharding, oftewel het kunnen en willen vasthouden aan een vastgestelde koers. Een derde aspect van morele moed heeft betrekking op het willen zijn van een moreel voorbeeld voor hun personeelsleden, leerlingen en andere betrokkenen. Schoolleiders in dit onderzoek zien het tonen van morele moed als een noodzaak om goed leiding te kunnen geven aan hun onderwijsinstelling.

INTRODUCTION: Obesity has been recognized as an increasing problem in the western countries. Obesity, determined as a single measurement of weight (and height) at a certain moment, has already been associated with an increased risk for several cancers. Nevertheless, weight change seems to be a more appropriate measure for adiposity in humans. AIM: Systematically review the effect of weight gain (throughout life) on the risk of several types of cancers. MATERIAL AND METHODS: We selected 58 studies, which investigated the relation of weight gain with breast cancer or/and ovarian cancer or/and endometrial cancer or/and prostate cancer or/and colorectal cancer. Furthermore, of all the studies we evaluated the study design, the characteristics of the study populations, the method of exposure assessment, specific cancer outcomes, confounding factors and effect modifiers. RESULTS: The studies discussed differed with respect to study design, sample size and confounding factors (within a certain cancer outcome). The majority of studies assessed weight gain information retrospectively (by recall), and were entailed by numerous biases. Only a few studies assessed weight gain prospectively. However, this studies only investigated the effect of short-term weight gain. Increases of risk for post-menopausal cancers in relation to weight gain were reported in many studies, however only in non-HRT users. Studies which also stratified on menopausal status, did not find this effect in pre-menopausal women. For the other cancers discussed, no consistent increases or decreases in risk were found. CONCLUSION: Weight gain seems to increase the risk for post-menopausal breast cancer. In contrast, weight gain does not seem to change the risk for pre-menopausal breast cancer. Ovarian cancer, endometrial cancer, prostate cancer and colon-rectal cancer were not studied as extensively as breast cancer in relation to weight gain. Before drawing any conclusions about these type of cancer, more la

INTRODUCTION: Obesity has been recognized as an increasing problem in the western countries. Obesity, determined as a single measurement of weight (and height) at a certain moment, has already been associated with an increased risk for several cancers. Nevertheless, weight change seems to be a more appropriate measure for adiposity in humans. AIM: Systematically review the effect of weight gain (throughout life) on the risk of several types of cancers. MATERIAL AND METHODS: We selected 58 studies, which investigated the relation of weight gain with breast cancer or/and ovarian cancer or/and endometrial cancer or/and prostate cancer or/and colorectal cancer. Furthermore, of all the studies we evaluated the study design, the characteristics of the study populations, the method of exposure assessment, specific cancer outcomes, confounding factors and effect modifiers. RESULTS: The studies discussed differed with respect to study design, sample size and confounding factors (within a certain cancer outcome). The majority of studies assessed weight gain information retrospectively (by recall), and were entailed by numerous biases. Only a few studies assessed weight gain prospectively. However, this studies only investigated the effect of short-term weight gain. Increases of risk for post-menopausal cancers in relation to weight gain were reported in many studies, however only in non-HRT users. Studies which also stratified on menopausal status, did not find this effect in pre-menopausal women. For the other cancers discussed, no consistent increases or decreases in risk were found. CONCLUSION: Weight gain seems to increase the risk for post-menopausal breast cancer. In contrast, weight gain does not seem to change the risk for pre-menopausal breast cancer. Ovarian cancer, endometrial cancer, prostate cancer and colon-rectal cancer were not studied as extensively as breast cancer in relation to weight gain. Before drawing any conclusions about these type of cancer, more la