Maternal risk of breast cancer following multiple births: a nationwide study in Sweden

The association between multiple births and subsequent maternal breast cancer risk was explored in a nested case-control study in Sweden encompassing 19,368 parous women with breast cancer diagnosed up to age 65 years, and 100,459 parous controls. Among cases and controls, there were 329 and 2,031 women, respectively, with a history of at least one live multiple birth. Compared with singleton mothers, breast cancer risk was 12 percent lower (odds ratio=0.088, 95 percent confidence interval=0.78–0.99) in women who had had a multiple birth. After stratification for age at diagnosis, evidence of a significant inverse association was found only in women aged 54 years or younger. Birth order of the multiple pregnancy had no apparent risk-modifying effect. Age at earliest multiple birth was unrelated to breast cancer risk. The inverse association between twinning and breast cancer risk may reflect protective physiological features of twin pregnancies. Further research is needed to investigate the role, if any, of in creased levels of steroid hormone-binding globulins in mothers of twins and the proposed inhibitory effects of human chorionic gonadotropin and -fetoprotein, both of which are increased during multiple gestations, on breast carcinogenesis. Breast feeding patterns in mothers of twins also may modify their risk of developing breast cancer.Ambors are with the Department of Cancer Epidemiology (Drs Lambe Ekbom, Adami) and Department of Social Medicine (Lambe), University Hospital, Uppsala, Sweden: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA (Drs Hsieb, Tsilib, Adami, Ekbom, Trichopoulos); UMASS Cancer Center, Worcester, MA, USA (Dr Hsieb). Address correspondece to Dr Lambe, Department of Cancer Epidemiology, University Hospital, S-751 85 Uppsala, Sweden. This project is funded by grants from the Swedish Cencer Societv. the Swedish Societv of Medicine. and the Wahlmarks Fund at Uppsala City Council.     

Case-control study on colon cancer regarding previous diseases and drug intake

Some diseases and drugs have previously been associated with increased risk for colon cancer. A case-control study on colon adenocarcinoma was conducted encompassing 329 cases and 658 controls. History of previous diseases and drug intake was assessed by questionnaire. Appendectomy was associated with a protective effect with odds ratio (OR) 0.5 and 95% confidence interval (CI) 0.2-0.9. Cholecystectomy was associated with increased risk, especially in females, for right sided and transverse colon cancer, OR 1.5 (CI 0.9-2.5) and OR 1.8 (CI 0.8-3.5), respectively. Ulcerative colitis increased the risk, OR 11 (CI 3.5-38). Also hyperplasia of the prostate gland and diabetes in men were related to an increased risk with OR 4.4 (CI 1.5-13) and OR 2.9 (CI 1.4-6.0), respectively. For men and women together diabetes mellitus yielded an increased OR of 1.7 (1.0-3.0). Regarding drugs somewhat increased risks were found for beta-2-stimulating agents, OR 1.9 (CI 0.6-5.4), benzodiazepine, OR 1.7 (CI 0.9-3.3), iron, OR 1.9 (CI 0.5-6.7), and paracetamol, OR 2.5 (0.6-8.5). Increased risks were found for hydralazine in men, OR 2.3 (CI 0.7-7.0), methyldopa in men, OR 4.3 (1.1-18), sulfonylurea, OR 2.9 (CI 1.2-6.7), and verapamil, OR 22 (CI 2.4-480). Somewhat decreased risk was found for indometacin, OR 0.6 (0.2-1.6).     

Selective inhibition of group II phospholipase A2 by quercetin

The influence of quercetin, chlorpromazine, aristolochic acid, and indomethacin on group I phospholipase A₂ (PLA₂) from porcine pancreas and on group II PLA₂ fromVipera russelli was compared. Quercetin and chlorpromazine were found to inhibit PLA₂ activity in lower concentrations (< 100M), while aristolochic acid and indomethacin were inhibitory only in higher concentrations (> 100M). The order of potency againstVipera PLA₂ was: quercetin >chlorpromazin aristolochic acid > indomethacin, while the order of potency against pancreatic PLA₂ was: chlorpromazine > aristolochic acid > indomethacin> quercetin. Thus, quercetin was a potent inhibitor towards group II PLA₂ (IC₅₀=2M), but a very weak inhibitor against group I PLA₂, with maximum 30% inhibition. Aristolochic acid and indomethacin were three to four times more potent towards group II PLA₂ than towards group I PLA₂, while chlorpromazine was equally potent towards the two PLA₂ types. Quercetin and chlorpromazine were also tested against two PLA₂ fractions purified from the plasma of septic shock patients; chlorpromazine was then equally potent towards the two PLA₂ fractions, whereas quercetin was a potent inhibitor of only one of the two PLA₂ fractions (IC₅₀=4M). Together, these results indicate that (1) different PLA₂ inhibitors have different potency depending on which type of PLA₂ they are used against, (2) quercetin selectively inhibits group II PLA₂ and may therefore be used to discriminate between different PLA₂ forms in biological materials, and (3) both PLA₂ of group I and group II are present in septic shock plasma.     

Interferon-beta treatment for patients with multiple sclerosis: the patients' perceptions of the side-effects

The aims of this study were to investigate (i) the self-reported frequency and intensity of systemic side-effects and their impact on the daily lives of patients suffering from Multiple Sclerosis (MS) and undergoing interferon-beta therapy and (ii) the self-reported frequency and perceptions of any local-tissue reactions. Forty patients aged 22 - 59 years (27 females) with relapsing/remitting MS were consecutively recruited for the study (17 on interferon-beta-1a and 23 on interferon-beta-1b). Two self-administered questionnaires were used before and after 1, 4, 8 and 16 weeks of therapy. The interferon therapy was found to be associated with flu-like symptoms. Most systemic side-effects were reported to be mild and to have little impact on the patients' daily lives. Asthenia and fatigue were more often rated as moderate or severe. The most frequently reported local-tissue side-effects were redness and local pain at the injection sites. A considerable inter-individual variation was found among patients regarding the perceptions of both the systemic and local side-effects. This suggests that it is of importance to identify early those patients who may need more support or other interventions to maintain a successful compliance. Multiple Sclerosis (2000) 6 349 - 354     

Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: no difference in related compared with unrelated transplant in first complete remission.

PURPOSE: The role of unrelated allogeneic stem-cell transplantation in acute lymphoblastic leukemia (ALL) patients is still not clear, and only limited data are available from the literature. We analyzed factors affecting clinical outcome of ALL patients receiving a related or unrelated stem-cell graft from matched donors. PATIENTS AND METHODS: The total study population was 264 adult patients receiving a myeloablative allogeneic stem-cell transplant for ALL at nine bone marrow transplantation centers between 1990 and 2002. Of these, 221 patients receiving a matched related or unrelated graft were analyzed. One hundred forty-eight patients received transplantation in complete remission; 62 patients were in relapse; and 11 patients were refractory to chemotherapy before transplant. Fifty percent of patients received bone marrow, and 50% received peripheral blood stem cell from a human leukocyte antigen-identical related (n = 103), or matched unrelated (n = 118) donor. RESULTS: Disease-free survival (DFS) at 5 years was 28%, with 76 patients (34%) still alive (2.2 to 103 months post-transplantation), and 145 deceased (65 relapses, transplant-related mortality, 45%). We observed an advantage regarding DFS in favor of patients receiving transplantation during their first complete remission (CR) in comparison with patients receiving transplantation in or after second CR (P =.014) or who relapsed (P <.001). We observed a clear trend toward improved survival in favor of B-lineage ALL patients compared with T-lineage ALL patients (P =.052), and Philadelphia chromosome-positive patients had no poorer outcome than Philadelphia chromosome-negative patients. Total-body irradiation-based conditioning improved DFS in comparison with busulfan (P =.041). CONCLUSION: Myeloablative matched related or matched unrelated allogeneic hematopoietic stem-cell transplantation in ALL patients should be performed in first CR.     

No association between immunohistochemical expression of p53, c-erbB-2, Ki-67, estrogen and progesterone receptors in female papillary thyroid cancer and ionizing radiation

An association has previously been reported between exposure to medical diagnostic ionizing radiation and papillary thyroid cancer in women. To further evaluate potential mechanisms in carcinogenesis, the expression of p53, c-erbB-2, as well as Ki-67, estrogen and progesterone receptors were analyzed by immunohistochemistry in 19 women exposed to X-rays and for comparison in nine women without such reported exposure. They all had papillary thyroid cancer. No difference was found between these groups. The results of this study showed that p53, c-erbB-2, Ki-67, estrogen and progesterone receptors are not involved in papillary thyroid cancer associated with exposure to medical diagnostic ionizing radiation.     

Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 polymorphisms with the pharmacokinetics of paclitaxel.

PURPOSE: To retrospectively evaluate the effects of six known allelic variants in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes on the pharmacokinetics of the anticancer agent paclitaxel (Taxol). EXPERIMENTAL DESIGN: A cohort of 97 Caucasian patients with cancer (median age, 57 years) received paclitaxel as an i.v. infusion (dose range, 80-225 mg/m(2)). Genomic DNA was analyzed using PCR RFLP or using Pyrosequencing. Pharmacokinetic variables for unbound paclitaxel were estimated using nonlinear mixed effect modeling. The effects of genotypes on typical value of clearance were evaluated with the likelihood ratio test within NONMEM. In addition, relations between genotype and individual pharmacokinetic variable estimates were evaluated with one-way ANOVA. RESULTS: The allele frequencies for the CYP2C8*2, CYP2C8*3, CYP2C8*4, CYP3A4*3, CYP3A5*3C, and ABCB1 3435C>T variants were 0.7%, 9.2%, 2.1%, 0.5%, 93.2%, and 47.1%, respectively, and all were in Hardy-Weinberg equilibrium. The population typical value of clearance of unbound paclitaxel was 301 L/h (individual clearance range, 83.7-1055 L/h). The CYP2C8 or CYP3A4/5 genotypes were not statistically significantly associated with unbound clearance of paclitaxel. Likewise, no statistically significant association was observed between the ABCB1 3435C>T variant and any of the studied pharmacokinetic variables. CONCLUSIONS: This study indicates that the presently evaluated variant alleles in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes do not explain the substantial interindividual variability in paclitaxel pharmacokinetics.     

Risk of suicide in men with low-risk prostate cancer

PurposeRisk of suicide is increased among men with prostate cancer. We investigated this association among men with low-risk cancer, usually detected by prostate specific antigen (PSA)-testing.Patients and MethodsRelative risk (RR) of suicide was calculated by use of Poisson regression analysis within the Prostate Cancer data Base Sweden (PCBaSe) 2.0, a nation-wide, population-based database, comparing 105,736 men diagnosed with prostate cancer between 1997–2009 to 528,658 matched prostate cancer-free men.ResultsDuring the first 6 months after diagnosis, there were 38 suicides among men with prostate cancer; incidence rate 0.73 per 1000 person-years (PY) and 30 suicides in the comparison cohort; 0.11 per 1000 PY, corresponding to a RR of suicide of 6.5 (95% confidence interval (CI) 4.0–10). Risk was highest among men with distant metastases, incidence rate 1.25 per 1000 PY, RR 10 (95% CI 5.1–21) but risk was also increased for men with low-risk tumours, incidence rate difference 0.45 per 1000 PY and RR 5.2 (95% CI 2.3–12) and across categories of socioeconomic status and comorbidity. Eighteen months after diagnosis, risk of suicide had decreased to 0.27 per 1000 PY, RR 1.0 (95% CI 0.68–1.5) for low-risk prostate cancer but remained increased among men with metastases, 0.57 per 1000 PY, RR 1.8 (95% CI 1.1–2.9).ConclusionAlthough the increase in absolute risk of suicide was modest, our findings reflect the severe psychological stress that prostate cancer patients may experience after diagnosis. The increased risk of suicide observed in men with prostate cancer, including low-risk, calls for increased awareness.     

Changes in dental conditions during a decade in a middle-aged and older Swedish population

A questionnaire measuring dental conditions was sent to 2708 individuals aged 55–79 years in O¨rebro County, who about 10 years earlier had been randomly selected for a similar study. The response rate was 68% (1848 individuals). Of those, 1665 had participated also in the 1989 study. The objectives were to study changes in dental conditions having occurred during a decade and to evaluate whether impairment in dental conditions among the participants had resulted in prosthodontic treatments. Only small changes in dental conditions were registered among those who participated both in 1989 and in 1999. Loss of a single tooth was the most frequently reported change. Ten per cent fewer reported that they had all teeth remaining in 1999 compared with conditions in 1989. The number of subjects wearing removable dentures increased only slightly. Although the reported changes in dental conditions were small, there had been a need for prosthodontic treatment in many of the subjects. Ten percent of the subjects reported that they had received FPD treatment during the past 10 years. To conclude, the present study showed that only small changes in dental conditions had occurred among the participants during a decade. Nevertheless, a substantial increase in the prevalence of prosthodontic appliances, especially of fixed restorations, was noted.