Joseph K. McLaughlin

Cancer risk among statin users: a population-based cohort study.

Hydroxymethylglutaryl‐CoA reductase inhibitors (statins) have been linked with potential chemopreventive effects; however, the data are conflicting. We conducted a population‐based cohort study using data from the Prescription Database of North Jutland County and the Danish Cancer Registry for the period 1989–2002. In a study population of 334,754 county residents, we compared overall and site‐specific cancer incidence among 12,251 statin users (≥2 prescriptions) with cancer incidence among nonusers and users of other lipid‐lowering drugs (n = 1,257). Statistical analyses were based on age‐standardization and Poisson regression analysis, adjusting for age, gender, calendar period and use of NSAIDs, hormone replacement therapy and cardiovascular drugs. We identified 398 cancer cases among statin users during a mean follow‐up period of 3.3 years (range 0–14 years). The age‐ and gender‐standardized incidence rates of cancer overall were 596 per 100,000 person‐years among statin users, 645 per 100,000 person‐years among nonusers and 795 per 100,000 person‐years among users of other lipid‐lowering drugs. Adjusted rate ratios for cancer overall among statin users were 0.86 (95% CI, 0.78–0.95) compared to nonusers and 0.73 (95% CI, 0.55–0.98) compared to users of other lipid‐lowering drugs. No significantly increased or decreased rate ratios were observed for any of the studied site‐specific cancers (liver, colorectum, lung, breast, prostate, female genital organs and lymphatic and haematopoietic tissue), but most estimates tended to be less than 1.0. Stratification by duration of follow‐up or number of prescriptions revealed no clear trends. In summary, individuals prescribed statins experienced a slightly reduced cancer incidence compared to population controls of nonusers and users of other lipid‐lowering drugs. Larger and longer‐term studies are needed to determine the potentially protective effect of statin use on cancer development.

Maternal levels of perfluorinated chemicals and subfecundity

BACKGROUNDnPerfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are ubiquitous man-made compounds that are possible hormonal disruptors. We examined whether exposure to these compounds may decrease fecundity in humans.nnnMETHODSnPlasma levels of PFOS and PFOA were measured at weeks 4-14 of pregnancy among 1240 women from the Danish National Birth Cohort recruited from 1996 to 2002. For this pregnancy, women reported time to pregnancy (TTP) in five categories (<1, 1-2, 3-5, 6-12 and >12 months). Infertility was defined as having a TTP of >12 months or received infertility treatment to establish this pregnancy.nnnRESULTSnLonger TTP was associated with higher maternal levels of PFOA and PFOS (P < 0.001). Compared with women in the lowest exposure quartile, the adjusted odds of infertility increased by 70-134 and 60-154% among women in the higher three quartiles of PFOS and PFOA, respectively. Fecundity odds ratios (FORs) were also estimated using Cox discrete-time models. The adjusted FORs were virtually identical for women in the three highest exposure groups of PFOS (FOR = 0.70, 0.67 and 0.74, respectively) compared with the lowest quartile. A linear-like trend was observed for PFOA (FOR = 0.72, 0.73 and 0.60 for three highest quartiles versus lowest quartile). When all quartiles were included in a likelihood ratio test, the trends were significant for PFOS and PFOA (P = 0.002 and P < 0.001, respectively).nnnCONCLUSIONSnThese findings suggest that PFOA and PFOS exposure at plasma levels seen in the general population may reduce fecundity; such exposure levels are common in developed countries.

Risk of cancer in a large cohort of nonaspirin NSAID users: a population-based study

There is increasing evidence of an inverse association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of colorectal cancer. However, data regarding other cancer sites are limited. Using data from the population-based North Jutland Prescription Database and the Danish Cancer Registry, we compared cancer incidence among 172u2009057 individuals prescribed nonaspirin NSAIDs with expected incidence (based on county-specific cancer rates) during a 9-year study period. A total of 6081 incident cancer cases were diagnosed among NSAID users vs 5722 expected (standardised incidence ratio (SIR) 1.1, 95% confidence interval (CI)1.0–1.1). The SIRs for colon and rectal cancer among persons who obtained 10 or more prescriptions were 0.7 (95% CI 0.6–0.9) and 0.6 (95% CI 0.4–0.9), respectively. Similarly, reduced risk estimates were found for stomach (SIR 0.7, 95% CI 0.4–1.1) and ovarian cancer (SIR 0.7, 95% CI 0.4–1.0). Standardised incidence ratios for other cancers among those with 10 or more prescriptions tended to be close to 1.0, except for lung, kidney, and prostate cancers with SIRs of 1.3 (95% CI 1.1–1.6), 1.4 (95% CI 0.9–2.1), and 1.6 (95% CI 1.3–2.0), respectively. We found protective associations of NSAIDs against colon, rectal, stomach, and ovarian cancer. Reasons for the increased risk for some cancer sites are not clear.

Angiotensin-converting enzyme inhibitors and the risk of cancer: a population-based cohort study in Denmark.

A recent observational study suggested that the use of angiotensin‐converting enzyme (ACE) inhibitors protects against cancer in general and against breast and female reproductive tract cancers in particular. To explore these hypotheses, the authors examined cancer risk among users of ACE inhibitors in North Jutland County, Denmark.

Fetal Growth Indicators and Perfluorinated Chemicals: A Study in the Danish National Birth Cohort

Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) are widespread persistent organic pollutants that have been associated with reduced birth weight at doses expected in many pregnant populations. The authors randomly selected 1,400 pregnant women and their newborns from the Danish National Birth Cohort (1996-2002) to investigate whether these compounds reduce organ growth. PFOS and PFOA were measured in maternal blood samples taken early in pregnancy. Placental weight, birth length, and head and abdominal circumferences were measured shortly after birth by trained midwives or nurses. Maternal PFOA levels in early pregnancy were associated with smaller abdominal circumference and birth length. For each ng/ml increase in PFOA, birth length decreased by 0.069 cm (95% confidence interval: 0.024, 0.113) and abdominal circumference decreased by 0.059 cm (95% confidence interval: 0.012, 0.106). An inverse association was also observed between PFOA and placental weight and head circumference, and a positive association was observed with newborn ponderal index, but none of these associations was statistically significant. Maternal PFOS levels were not associated with any of the five fetal growth indicators. These findings suggest that fetal exposure to PFOA but not PFOS during organ development may affect the growth of organs and the skeleton.

Risk of hospitalization resulting from upper gastrointestinal bleeding among patients taking corticosteroids: A register-based cohort study

PURPOSEnWe assessed the risk of hospitalization for upper gastrointestinal bleeding among patients using systemic corticosteroids, accounting for the use of other drugs that may increase the risk of bleeding.nnnSUBJECTS AND METHODSnWe conducted a population-based cohort study in North Jutland County, Denmark. Data on the use of corticosteroids, nonsteroidal anti-inflammatory drugs, aspirin, and anticoagulants during 1991 to 1995 were obtained from a countywide prescription database. All hospitalizations because of upper gastrointestinal bleeding were identified through the Hospital Discharge Registry. The observed numbers of patients with gastrointestinal bleeding in various exposure categories among corticosteroid users were compared with the expected number based on the North Jutland population who did not receive prescriptions for any of the drugs under study.nnnRESULTSnA total of 45,980 patients accrued 18,379 person-years of corticosteroid use. There were 109 hospital admissions for gastrointestinal bleeding among corticosteroid users, compared with 26 expected, yielding a relative risk of 4.2 [95% confidence interval (CI): 3.4 to 5.0]. Among corticosteroid users who did not use other drugs associated with gastrointestinal bleeding, the relative risk was 2.9 (95% CI: 2.2 to 3.7). The relative risk decreased further to 1.9 (95% CI: 1.4 to 2.5) when current corticosteroid usage was compared with former usage.nnnCONCLUSIONnWe observed an increased risk of hospitalization because of upper gastrointestinal bleeding among patients prescribed corticosteroids, especially among those who use other medications. Confounding from the underlying disease may also have contributed to the observed increase in risk.

A Cohort Study of Antihypertensive Medication Use and Breast Cancer Among Danish Women

BackgroundIt has been suggested that specific antihypertensive medications (AHT) may either increase or decrease breast cancer risk.MethodsWe studied breast cancer incidence among 49,950 women in North Jutland, Denmark in order to determine if breast cancer risk is associated with specific classes of AHT use. Poisson regression analyses were used to calculate rate ratios for ever or exclusive use of each class of AHT, number of prescriptions for AHT, and years of follow-up.ResultsThere was no statistically significant association between ever use of any AHT overall (RRxa0=xa00.95; 95% CIxa0= 0.81–1.10) or any specific class of AHT (diuretics, beta blockers, calcium channel blockers (CCBs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin II antagonists) and breast cancer.ConclusionsThis study should offer further reassurance to women currently using AHT that their medication use is unlikely related to breast cancer risk.

Vitamin D intake and breast cancer risk: a case–control study in Italy

BACKGROUNDnVitamin D has been suggested to play a protective role against several cancers, including breast cancer.nnnPATIENTS AND METHODSnWe used data from a case-control study conducted in Italy from 1991 to 1994 to study the relation between dietary intake of vitamin D and breast cancer risk. Subjects were 2569 women with incident, histologically confirmed breast cancer and 2588 hospital controls. Odds ratios (ORs) and 95% confidence intervals (CIs) according to deciles of vitamin D intake were estimated by multiple logistic regression models.nnnRESULTSnAfter allowance for major risk factors for breast cancer and dietary covariates including calcium and energy intake, there was no association with vitamin D up to the seventh decile. Thereafter, the OR declined, so that the overall trend was statistically significantly inverse. The OR for subjects in the three highest deciles of consumption compared with those in the lowest ones combined was 0.79 (95% CI 0.70-0.90). Intake of vitamin D >3.57 microg or 143 IU appeared to have a protective effect against breast cancer. The inverse association was consistent across strata of menopausal status.nnnCONCLUSIONSnThis study adds to the existing evidence that vitamin D intake in inversely associated with breast cancer risk.

COX-2-selective inhibitors and the risk of upper gastrointestinal bleeding in high-risk patients with previous gastrointestinal diseases: a population-based case–control study

Background :u2002Clinical trials have suggested that cyclo‐oxygenase‐2‐selective inhibitors are associated with a lower risk of upper gastrointestinal bleeding than are non‐selective, non‐aspirin, non‐steroidal anti‐inflammatory drugs. This has not yet been confirmed in studies of patients with an increased susceptibility to upper gastrointestinal bleeding.

Incidence and predictors of end stage renal disease among low-income blacks and whites.

We evaluated whether black race is associated with higher incidence of End Stage Renal Disease (ESRD) among a cohort of blacks and whites of similar, generally low socioeconomic status, and whether risk factor patterns differ among blacks and whites and explain the poorly understood racial disparity in ESRD. Incident diagnoses of ESRD among 79,943 black and white participants in the Southern Community Cohort Study (SCCS) were ascertained by linkage with the United States Renal Data System (USRDS) from 2002 through 2009. Person-years of follow up were calculated from date of entry into the SCCS until date of ESRD diagnosis, date of death, or September 1, 2009, whichever occurred first. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for incident ESRD among black and white participants in relation to baseline characteristics. After 329,003 person-years of follow-up, 687 incident cases of ESRD were identified in the cohort. The age-adjusted ESRD incidence rate was 273 (per 100,000) among blacks, 3.5-fold higher than the rate of 78 among whites. Risk factors for ESRD included male sex (HRu200a=u200a1.6; 95% CI 1.4–1.9), low income (HRu200a=u200a1.5; 95% CI 1.2–1.8 for income below vs. above