Biomedical subjects

P H Peeters

Publications and source records attributed to P H Peeters.

At least 19 recordsLinked to original sources

PubMed2006

Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions.

It is becoming increasingly evident that single-locus effects cannot explain complex multifactorial human diseases like cancer. We applied the multi-factor dimensionality reduction (MDR) method to a large cohort study on gene-environment and gene-gene interactions. The study (case-control nested in the EPIC cohort) was established to investigate molecular changes and genetic susceptibility in relation to air pollution and environmental tobacco smoke (ETS) in non-smokers. We have analyzed 757 controls and 409 cases with bladder cancer (n=124), lung cancer (n=116) and myeloid leukemia (n=169). Thirty-six gene variants (DNA repair and metabolic genes) and three environmental exposure variables (measures of air pollution and ETS at home and at work) were analyzed. Interactions were assessed by prediction error percentage and cross-validation consistency (CVC) frequency. For lung cancer, the best model was given by a significant gene-environment association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism, the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the exposure variable 'distance from heavy traffic road', an indirect and robust indicator of air pollution (mean prediction error of 26%, P<0.001, mean CVC of 6.60, P=0.02). For bladder cancer, we found a significant 4-loci association between the BER APE1-Asp148Glu polymorphism, the DSBR RAD52-3'-untranslated region (3'-UTR) polymorphism and the metabolic gene polymorphisms COMT-Val158Met and MTHFR-677C>T (mean prediction error of 22%, P<0.001, mean CVC consistency of 7.40, P<0.037). For leukemia, a 3-loci model including RAD52-2259C>T, MnSOD-Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P<0.001) and a maximum CVC of 4.40 (P=0.086). The MDR method seems promising, because it provides a limited number of statistically stable interactions; however, the biological interpretation remains to be understood.

Drug Resistance, Multiple↗

PubMed2006

Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition.

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.

Adenocarcinoma↗

PubMed2005

DNA repair polymorphisms and cancer risk in non-smokers in a cohort study.

Environmental carcinogens contained in air pollution, such as polycyclic aromatic hydrocarbons, aromatic amines or N-nitroso compounds, predominantly form DNA adducts but can also generate interstrand cross-links and reactive oxygen species. If unrepaired, such lesions increase the risk of somatic mutations and cancer. Our study investigated the relationships between 22 polymorphisms (and their haplotypes) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases (bladder cancer, 131; lung cancer, 134; oral-pharyngeal cancer, 41; laryngeal cancer, 47; leukaemia, 179; death from emphysema and chronic obstructive pulmonary disease, 84). The design was a case-control study nested within a prospective investigation. Among the many comparisons, few polymorphisms were associated with the diseases at the univariate analysis: XRCC1-399 Gln/Gln variant homozygotes [odds ratios (OR) = 2.20, 95% confidence intervals (CI) = 1.16-4.17] and XRCC3-241 Met/Met homozygotes (OR = 0.51, 95% CI = 0.27-0.96) and leukaemia. The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1-399Gln/Gln in lung cancer (OR = 0.22, 95% CI = 0.05-0.98), and confirmed an opposite effect (OR = 2.47, 95% CI = 1.02-6.02) in the leukaemia group. Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia (OR = 1.28, 95% CI = 1.02-1.61), bladder cancer (OR = 1.38, 95% CI = 1.06-1.79) and possibly other cancer risks. Further investigations of the combined effects of polymorphisms within these DNA repair genes, smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process.

Adult↗

PubMed2001

[Breast complaints during the Dutch nationwide breast cancer screening program: increased risk of referral and of breast cancer].

OBJECTIVE: To determine the prevalence of breast complaints reported on a questionnaire among participants in the first round of the national breast cancer screening programme in the Netherlands, and to assess the relationship between these complaints and referral and diagnosis of breast cancer. DESIGN: Retrospective controlled study. METHOD: Women in the South screening region of the Dutch nation-wide breast cancer screening programme (Stichting Bevolkingsonderzoek Borstkander Zuid (BoBZ)) received a medical questionnaire together with the invitation for participation in the screening programme. This questionnaire was only reviewed by the radiologist if there were doubts concerning referral. The study assessed whether participants with these complaints had higher risks of referral and screen-detected breast cancer than those without these complaints. In this study two random and independent samples were drawn from the screening files: 1116 women who attended the first screening round and 1113 women who were referred for medical checkup in the same screening round. RESULTS: The prevalence of breast complaints reported in the first screening round was 5.1% (95% CI = 3.9-6.6). More than half of the complaints included pain not related to menses; nipple secretion; changes in skin (retraction or discolouration) or tumours. The referral risk for women with these complaints was more than twice that for women without complaints (adjusted odds ratio (OR) = 2.3; 95% CI = 1.4-3.8) and their risk of screen-detected breast cancer was more than three times as high (adjusted OR = 3.3; 95% CI = 1.4-3.8). Up to 5.8% of the screen-detected breast cancers could be attributed to the breast complaints. CONCLUSION: Breast complaints at the time of breast cancer screening increased the risk of breast cancer being detected, but it is not clear as yet whether the screening will benefit from the explicit incorporation of questions regarding complaints.

Adult↗

PubMed2001

[Diagnostics in clinically occult, radiologically suspect breast lesions more often surgery than needle diagnostics with image monitoring].

OBJECTIVE: To inventory the diagnostic methods used in patients with clinically occult, radiologically suspect breast lesions. DESIGN: Enquiry. METHOD: The departments of radiology of all Dutch hospitals were sent a list in January 2000 containing questions concerning the number of thread localizations in 1999 and the use of cytological or histological needle diagnostics with image monitoring prior to surgical intervention in clinically occult, radiologically suspect breast lesions. Of the 120 questionnaires mailed, 74 (62%) were completed and returned by clinics throughout the country. RESULTS: Fifty-one of the 74 hospitals (69%) had prior to operation carried out histological or cytological examinations and in these 51 hospitals this was done in 1743 of the 2857 lesions (61%): fine-needle aspiration cytology was performed in 1046 (/1743 = 60%; /4140 lesions in all 74 hospitals = 25%) and/or histological needle biopsy in 784 (45%; /4140 = 19%). CONCLUSION: In less than half of all non-palpable breast abnormalities non-surgical methods of diagnosis are used, histological needle biopsy less often than fine needle aspiration cytology.

Biopsy↗

PubMed2001

Cost comparison between stereotactic large-core-needle biopsy versus surgical excision biopsy in The Netherlands.

Yearly, approximately 7200 Dutch women with non-palpable breast lesions are referred for a diagnostic surgical excision biopsy. Recently, less invasive alternatives such as stereotactic large-core-needle biopsy have emerged. The aim of this study was to compare the costs of surgical excision biopsy and large-core-needle biopsy. As stereotactic equipment is expensive, the costs of large-core-needle biopsy depend on the extent of centralisation of this facility. Therefore, we assessed the extent of economies of scale in four different scenarios of (de)centralisation. We collected cost data in five Dutch hospitals. The cost of surgical excision biopsy amounted to 1184 Euros. In cases where large-core-needle biopsy would be employed decentralised in all 114 hospitals in The Netherlands, the average costs were estimated to be 1186 Euros compared with 572 Euros in a centralised scenario with involvement of 10 hospitals. Therefore, centralisation of stereotactic equipment for core-needle biopsies would be advisable from an economic perspective.

Biopsy↗

PubMed2001

Determinants of circulating insulin-like growth factor (IGF)-I and IGF binding proteins 1-3 in premenopausal women: physical activity and anthropometry (Netherlands).

OBJECTIVE: Epidemiologic studies suggest that subjects with elevated plasma concentrations of insulin-like growth factor (IGF)-I are at increased risk of developing cancer. The objective of our study was to assess whether cancer risk factors such as lack of physical activity, obesity, and central body fat distribution are associated with plasma levels of IGF-I and related proteins (i.e. IGF binding proteins 1-3 and C-peptide). METHODS: A cross-sectional study was conducted in a population of 225 premenopausal women, aged 49-57, participating in the Prospect-EPIC study in the Netherlands. Plasma concentrations of IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, and C-peptide were determined. On the day of blood collection height, weight, and waist and hip circumference were measured. Habitual physical activity was assessed using a validated self-administered questionnaire. RESULTS: Mean concentrations of plasma IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, and C-peptide were 156.1, 14.3, 434.4, 3062, and 2.86 ng/ml, respectively. Women in the highest tertile for physical activity had lower plasma concentrations of IGF-I, IGFBP-3, and C-peptide, and higher concentrations of IGFBP-1 and IGFBP-2, as compared to women in the lowest tertile. However, these differences were not statistically significant. BMI and related measures were significantly inversely associated with IGFBP-1 and IGFBP-2, and positively with IGFBP-3 and C-peptide. Linear regression analyses showed that the non-significant association of physical activity with components of the plasma IGF system was further attenuated by adjusting for obesity and central body fat distribution. CONCLUSIONS: Our data suggest that an active lifestyle is not independently associated with the plasma IGF system. We did confirm that a lean body shape is associated with higher concentrations of IGFBP-1 and IGFBP-2, and possibly also with lower concentrations of IGF-I and IGFBP-3.

Aged↗

PubMed2001

Prospect-EPIC Utrecht: study design and characteristics of the cohort population. European Prospective Investigation into Cancer and Nutrition.

The European Prospective Investigation into Cancer and Nutrition (EPIC), which has been established in order to investigate the relations between nutrition and cancer, was initiated in 1990 and involves 10 European countries with heterogeneous dietary patterns and differing cancer incidence rates. This manuscript presents the design, recruitment and baseline characteristics of the Prospect-EPIC cohort co-ordinated in Utrecht, The Netherlands. The cohort is based on volunteers recruited among women participating in a regional breast cancer screening program. It comprises of 17,357 subjects aged 50-69 years at enrolment from Utrecht and vicinity, who have consented to participate in the study and its follow-up. Each participant filled out a general questionnaire and a food frequency questionnaire. Participants were also physically examined and have donated a blood sample. Participation rate was 34.5%. Blood samples were donated by most participants (97.5%) and detailed informed consents were obtained from 87.4% of participants. Mean age at enrolment was 57 years. Anthropometric, lifestyle and morbidity characteristics of the cohort population did not differ largely from those of similar study populations in The Netherlands. Based on the Prospect-EPIC population, we intend to conduct prospective total cohort, nested case-control or case-cohort studies, in order to investigate relations between consumption of certain food groups or nutrients and chronic diseases, including hormone dependant cancers such as breast, colon, endometrial and ovary cancers.

Aged↗

PubMed2001

Impact of stereotactic large-core needle biopsy on diagnosis and surgical treatment of nonpalpable breast cancer.

INTRODUCTION: Stereotactic large-core needle biopsy is increasingly replacing needle-localized breast biopsy for the diagnosis of nonpalpable breast disease. In this prospective study, the impact of the introduction of this technique on diagnosis and surgical treatment of nonpalpable breast cancer was assessed in two hospitals in The Netherlands. PATIENTS AND METHODS: A total of 84 patients with nonpalpable breast cancer, diagnosed by means of stereotactic large-core needle biopsy (needle biopsy group) were compared with 80 patients diagnosed with nonpalpable breast cancer before the introduction of large-core needle biopsy. These patients were diagnosed by means of needle-localized open breast biopsy (control group). Clinical outcome measures evaluated included: duration of diagnostic and therapeutic intervals and number of surgical procedures required for complete surgical treatment. Subgroup analysis was performed for the category of microcalcifications without tissue distortion. RESULTS: For the needle biopsy group, the median interval between initial referral to the surgeon and the availability of histological diagnosis was 9 days and the interval between initial referral and complete surgical treatment was 31 days. These intervals were significantly longer for the control group (19 days and 44 days respectively); 75% of patients in the needle biopsy group were treated in a single step surgical procedure compared to 16% of the patients in the control group (67 vs 25% respectively for the subgroup). The mean number of surgical procedures required to complete surgical treatment was 1.31 for needle biopsy group vs 1.91 for the open biopsy group (1.46 vs 1.84 for the subgroup). CONCLUSION: Introduction of stereotactic large-core needle biopsy leads to a reduction of the time to diagnosis and the time to complete surgical treatment of nonpalpable breast cancer. It also reduces the number of surgical procedures required for complete surgical treatment of nonpalpable breast cancer. The benefits of large-core needle biopsy may also be anticipated for patients with microcalcifications without tissue distortion.

Adult↗

PubMed2001

Oral contraceptive use in relation to age at menopause in the DOM cohort.

BACKGROUND: We investigated the hypothesis that long-term use of oral contraceptives (OCs), in particular high-dose OCs, could postpone age at menopause. METHODS: Data was used from 8701 women who participated in a breast cancer screening programme in Utrecht (DOM-3 cohort), and who did not use hormone replacement therapy (HRT) or OCs in the 4 years prior to their last menses. Data on OC-use, menopausal status, age at menopause, year of birth, parity, smoking behaviour, socio-economic status, body mass index and age at menarche was available. Use of high-dose OCs has been defined in this study as OC-use before 1972. The data was analysed by means of linear regression and Cox's proportional hazards analysis. Women still menstruating, women with surgical menopause and women lost to follow-up were censored at their last known date of menstruation. Endpoint was the natural menopause (n = 4589). RESULTS: The use of high-dose OCs advanced the onset of menopause by approximately 1.2 months for every year of OC-use compared with no OC-use. High-dose OC-use for > or = 3 years, adjusted for confounding variables, increased the risk of earlier menopause compared with no OC-use (adjusted hazard ratio 1.12; 95% CI 1.03--1.21). The use of lower dose OCs did not increase the risk of earlier menopause (adjusted hazard ratio 1.00; 95% CI 0.91--1.09). CONCLUSIONS: These results are inconsistent with the hypothesis that long-term use of OCs could postpone the onset of menopause by inhibiting follicle depletion. Possible explanations are discussed.

Age Factors↗

PubMed2001

Risk factors for cancellation of stereotactic large core needle biopsy on a prone biopsy table.

Among patients undergoing stereotactic needle biopsy of the breast on a prone biopsy table, a substantial proportion of planned procedures are terminated prematurely. This study was undertaken to identify risk factors for cancellation of these procedures and to derive a clinical rule for predicting cancellation. Risk factors for cancellation were assessed in a group of 476 consecutive patients with non-palpable lesions planned for large core needle biopsy. 64 (13%) of these planned procedures were cancelled. Multivariate regression analysis was applied to identify independent risk factors for cancellation. Validation took place by applying the logistic rule on a validation set, including 5 cancelled and 35 successful biopsy procedures. Mammograms that were difficult to interpret owing to extremely dense breast tissue, axillary location of the non-palpable lesion, body mass index below 20, less than 15 mm distance from the lesion to the chest wall or the presence of more than one non-palpable lesion were identified as independent risk factors. The logistic rule discriminated patients with successful and cancelled biopsy procedures with a receiver operator characteristic (ROC) area of 0.72. In the validation set, the area under the ROC curve was 0.92. The prediction rule, based on mammographic and clinical findings, discriminated patients with successful and cancelled needle biopsy procedures to a certain extent. The risk of cancellation of the stereotacic biopsy procedure is considerable in cases of very dense breast tissue or the presence of multiple risk factors.

Biopsy, Needle↗

PubMed2001

Urinary phytoestrogens and postmenopausal breast cancer risk.

Phytoestrogens are defined as plant substances that are structurally or functionally similar to estradiol. We report the associations of two major phytoestrogens, genistein and enterolactone, with breast cancer risk, using urinary specimens collected 1-9 years before breast cancer was diagnosed. The subjects were 88 breast cancer cases and 268 controls, selected from a cohort of postmenopausal women (n = 14,697) who participated in a breast cancer screening program. Mean levels of urinary genistein and enterolactone were determined by time resolved fluoroimmunoassay, using an average of two overnight urinary samples obtained from each participant on the first and the second screening rounds with a time interval of approximately 1 year. Odds ratios (ORs) of the highest to the lowest tertile of urinary phytoestrogen/creatinine concentrations and 95% confidence intervals (CIs) were computed. Higher urinary genistein excretion was weakly and nonsignificantly associated with a reduced breast cancer risk. OR for the highest tertile compared with lowest tertile was 0.83; 95% CI, 0.46-1.51. Higher urinary enterolactone excretion was weakly and nonsignificantly associated with an increased breast cancer risk. OR for the highest tertile compared with the lowest tertile was 1.43; 95% CI, 0.79-2.59. Tests for trends for both phytoestrogens were nonsignificant. We were not able to detect the previously reported protective effects of genistein and enterolactone on breast cancer risk in our postmenopausal population of Dutch women. Such an effect may be smaller than expected and/or limited to specific subgroups of the population.

4-Butyrolactone↗

PubMed2000

Long-term oral contraceptive use increases breast cancer risk in women over 55 years of age: the DOM cohort.

The role of past oral contraceptive use in the development of breast cancer is unclear, particularly in postmenopausal women. The authors investigated this relationship among pre- and postmenopausal middle-aged women in a nested case-control study within the population-based DOM cohort, Utrecht, the Netherlands. Among a total population of 12,184 women followed up for an average of 7.5 years, 309 breast cancer cases aged 42 to 63 years, diagnosed from November 1982 through May 1996, and 610 controls were examined. Overall, duration of oral contraceptive use was not clearly related to breast cancer. In women older than 55 years, however, oral contraceptive use for more than 10 years was associated with a 2-fold increased risk of breast cancer (odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.0). We conclude that long duration of oral contraceptive use increases the risk of breast cancer in women over 55 years of age but not in younger women.

Adult↗

PubMed2000

Diagnostic accuracy of needle-localized open breast biopsy for impalpable breast disease.

BACKGROUND: Needle-localized open breast biopsy (NLBB) is considered the gold standard procedure for the diagnosis of impalpable breast disease. In an observational follow-up study the sensitivity and negative predictive value of this procedure was determined in a clinical population with long-term follow-up. METHODS: Some 199 consecutive patients with a benign histological diagnosis on NLBB were followed for the occurrence of breast cancer, using information from the Dutch National Morbid-Anatomical Record Department. Based on a review of mammograms and histological slides, an expert panel decided whether the carcinomas detected during follow-up were newly developed, or were present already at the time of the NLBB. RESULTS: After a median follow-up of 60.5 months, seven carcinomas were detected. At panel review, six appeared to have been missed by NLBB. The sensitivity of NLBB was 99 per cent after 2 years of follow-up, but dropped to 96 per cent after 5 years. Similarly, the negative predictive value dropped from 99 per cent after 2 years to 94 per cent after 5 years of follow-up. CONCLUSION: NLBB is an accurate diagnostic procedure for the evaluation of impalpable breast disease. However, with longer follow-up the accuracy becomes lower than generally reported.

Adult↗

PubMed2000

Diagnostic accuracy of large-core needle biopsy for nonpalpable breast disease: a meta-analysis.

For the evaluation of non-palpable lesions of the breast, image-guided large-core needle biopsies are increasingly replacing needle-localized open breast biopsies. In this study, the diagnostic accuracy of this minimally invasive technique was evaluated by reviewing the available literature. Five cohort studies were included in a meta-analysis. Sensitivity rate, histological agreement between needle biopsy and subsequent surgery or long-term mammographic follow-up and clinical consequences for different disease prevalences were assessed. The sensitivity rate of large-core needle biopsy for the diagnosis of breast cancer was high (97%). The reclassified agreement rate between core biopsy and subsequent surgical biopsy or long-term mammographic follow-up was also high (94%). In case of 20% breast cancer prevalence among women referred after screening (as in the US), the risk of breast cancer despite benign large-core needle biopsy result is less than 1%. In European countries, however, prevalence of breast cancer among referred women is 60-70%. This would result in a risk of breast cancer despite benign large-core needle biopsy result of 4-6%. The results of this meta-analysis indicate that the image guided large-core needle biopsy is a promising alternative for the needle localized breast biopsy. However, additional research is needed to explore the limiting factors of the technique. Without such detailed knowledge, a benign histological diagnosis on large-core needle biopsy in countries with high prevalence of malignancy among referred women should be interpreted with caution.

Biopsy, Needle↗

PubMed2000

Functional results after treatment of hip fracture: a multicentre, prospective study in 215 patients.

OBJECTIVE: To find out which factors influence outcome after a fractured hip, so that the optimum treatment may be chosen for each patient. DESIGN: Prospective cohort study. SETTING: 3 teaching and 2 rural hospitals, The Netherlands. SUBJECTS: 215 patients aged 55-102 years (median 82) who presented with a fractured hip during 1994. INTERVENTIONS: Interviews shortly after the injury and 4 and 12 months later, study of radiographs, and evaluation of casenotes. MAIN OUTCOME MEASURES: Mobility and functional recovery. RESULTS: 38 patients had died by the 4-month follow up, at which time 64/177 (36%) had regained the level of mobility that they had before the injury. At 12 months the figure was 58/148 (39%). The corresponding figures for functional recovery were 52/177 (29%) and 36/148 (24%). Factors that militated against recovery were increasing age, coexisting diseases, general complications and local complications. CONCLUSIONS: The chance of a patient with a hip fracture making any further recovery after 4 months is minimal. Local complications are the most important risk factor.

Aged↗

PubMed2000

Age at menopause, body mass index, and the risk of colorectal cancer mortality in the Dutch Diagnostisch Onderzoek Mammacarcinoom (DOM) cohort.

We investigated whether age at menopause is associated with subsequent mortality from colorectal cancer along with the possible modification of this association by body mass index. Our data are from the Diagnostisch Onderzoek Mammacarcinoom cohort of 10,671 postmenopausal women in the Netherlands, enrolled between 1974 and 1977, with a median follow-up of 18 years. During this follow-up, 95 women died of colorectal cancer. Women 49 years of age or older at menopause showed a lower risk of colorectal cancer mortality compared with women younger than 49 at menopause. This protective effect, however, was found only among nonoverweight women (< or =24 kg/m2), for whom the hazard ratio was 0.46 (95% confidence interval = 0.21-1.03). In larger women, the hazard ratio was 1.17 (95% confidence interval = 0.68-2.00).

Age Factors↗

PubMed2000

Hypertension and breast cancer risk in a 19-year follow-up study (the DOM cohort). Diagnostic investigation into mammarian cancer.

BACKGROUND: To investigate whether hypertension and the use of anti-hypertensive drugs are associated with breast cancer risk. METHODS: This was a prospective study of 11, 011 women living in Utrecht, the Netherlands, aged 50-65 years at enrolment in a breast cancer screening project (DOM cohort). Women attended screening rounds between 1974 and 1985 at which blood pressure was measured and information on drug use and breast cancer risk factors was ascertained. Since 1974 (median follow-up time 19 years), information on breast cancer occurrence and death has been registered. Hypertension was defined as a systolic blood pressure > 160 mmHg or a diastolic blood pressure > 95 mmHg or current use of drugs for the indication hypertension. Cox's regression analysis was used to investigate the association between hypertension (treated or untreated) and subsequent breast cancer risk. Analyses were adjusted for age, body mass index, height, parity, familial breast cancer, smoking and oral contraceptive use. RESULTS: A total of 523 women were diagnosed with breast cancer. Hypertensive women experienced a statistically significant increased breast cancer risk of 23% (age-adjusted hazard ratio (HRa) = 1.23; 95% confidence interval (CI) 1.01 -1.49). After adjustment for all confounders, the increase was 14% (HR = 1.14; 95% CI 0.93-1.40). The decline in risk was mainly attributable to the effect of BMI. The risk was similar in treated (HR = 1.22; 95% CI 0.91-1.63) and untreated hypertensive women (HR = 1.13; 95% CI 0.91-1.40). CONCLUSION: These results do not support an association between hypertension and breast cancer, and if there is a link, it is likely to be positive and relatively small in size (+14%). This relation, if present, is not attributable to anti-hypertensive drugs, since the relation is also present in non-drug users.

Aged↗