Andrea Z. LaCroix

Bio: Andrea Z. LaCroix is an academic researcher from Fred Hutchinson Cancer Research Center. The author has contributed to research in topics: Women's Health Initiative & Osteoporosis. The author has an hindex of 88, co-authored 273 publications receiving 25538 citations. Previous affiliations of Andrea Z. LaCroix include Group Health Cooperative & University of California, San Diego.

Low-Fat Dietary Pattern and Risk of Colorectal Cancer: The Women's Health Initiative Randomized Controlled Dietary Modification Trial

Abstract: ContextObservational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer, necessitating a primary prevention trial.ObjectiveTo evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women.Design, Setting, and ParticipantsThe Women’s Health Initiative Dietary Modification Trial, a randomized controlled trial conducted in 48 835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States.InterventionsParticipants were randomly assigned to the dietary modification intervention (n = 19 541; 40%) or the comparison group (n = 29 294; 60%).The intensive behavioral modification program aimed to motivate and support reductions in dietary fat, to increase consumption of vegetables and fruits, and to increase grain servings by using group sessions, self-monitoring techniques, and other tailored and targeted strategies. Women in the comparison group continued their usual eating pattern.Main Outcome MeasureInvasive colorectal cancer incidence.ResultsA total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 (SD, 1.7) years. Intervention group participants significantly reduced their percentage of energy from fat by 10.7% more than did the comparison group at 1 year, and this difference between groups was mostly maintained (8.1% at year 6). Statistically significant increases in vegetable, fruit, and grain servings were also made. Despite these dietary changes, there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period. There were 201 women with invasive colorectal cancer (0.13% per year) in the intervention group and 279 (0.12% per year) in the comparison group (hazard ratio, 1.08; 95% confidence interval, 0.90-1.29). Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status (P = .01 for each). Colorectal examination rates, although not protocol defined, were comparable between the intervention and comparison groups. Similar results were seen in analyses adjusting for adherence to the intervention.ConclusionIn this study, a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up.Clinical Trials RegistrationClinicalTrials.gov Identifier: NCT00000611

Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer

Abstract: We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.

Association between alcohol and cardiovascular disease:Mendelian randomisation analysis based on individual participant data

Abstract: OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies. PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.

Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer

Abstract: We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.

Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial

Abstract: Context Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain Objective To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States Design Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 85 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998 Interventions Participants received conjugated equine estrogens, 0625 mg/d, plus medroxyprogesterone acetate, 25 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102) Main outcomes measures The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes Results On May 31, 2002, after a mean of 52 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits This report includes data on the major clinical outcomes through April 30, 2002 Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 129 (102-163) with 286 cases; breast cancer, 126 (100-159) with 290 cases; stroke, 141 (107-185) with 212 cases; PE, 213 (139-325) with 101 cases; colorectal cancer, 063 (043-092) with 112 cases; endometrial cancer, 083 (047-147) with 47 cases; hip fracture, 066 (045-098) with 106 cases; and death due to other causes, 092 (074-114) with 331 cases Corresponding HRs (nominal 95% CIs) for composite outcomes were 122 (109-136) for total cardiovascular disease (arterial and venous disease), 103 (090-117) for total cancer, 076 (069-085) for combined fractures, 098 (082-118) for total mortality, and 115 (103-128) for the global index Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures The absolute excess risk of events included in the global index was 19 per 10 000 person-years Conclusions Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 52-year follow-up among healthy postmenopausal US women All-cause mortality was not affected during the trial The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD

2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

Abstract: Preamble and Transition to ACC/AHA Guidelines to Reduce Cardiovascular Risk S2 The goals of the …

Randomized Trial of Estrogen Plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal Women

Abstract: Context.—Observational studies have found lower rates of coronary heart disease (CHD) in postmenopausal women who take estrogen than in women who do not, but this potential benefit has not been confirmed in clinical trials.Objective.—To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease.Design.—Randomized, blinded, placebo-controlled secondary prevention trial.Setting.—Outpatient and community settings at 20 US clinical centers.Participants.—A total of 2763 women with coronary disease, younger than 80 years, and postmenopausal with an intact uterus. Mean age was 66.7 years.Intervention.—Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily (n=1380) or a placebo of identical appearance (n=1383). Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment were taking it at the end of 1 year, and 75% at the end of 3 years.Main Outcome Measures.—The primary outcome was the occurrence of nonfatal myocardial infarction (MI) or CHD death. Secondary cardiovascular outcomes included coronary revascularization, unstable angina, congestive heart failure, resuscitated cardiac arrest, stroke or transient ischemic attack, and peripheral arterial disease. All-cause mortality was also considered.Results.—Overall, there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes: 172 women in the hormone group and 176 women in the placebo group had MI or CHD death (relative hazard [RH], 0.99; 95% confidence interval [CI], 0.80-1.22). The lack of an overall effect occurred despite a net 11% lower low-density lipoprotein cholesterol level and 10% higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group (each P<.001). Within the overall null effect, there was a statistically significant time trend, with more CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5. More women in the hormone group than in the placebo group experienced venous thromboembolic events (34 vs 12; RH, 2.89; 95% CI, 1.50-5.58) and gallbladder disease (84 vs 62; RH, 1.38; 95% CI, 1.00-1.92). There were no significant differences in several other end points for which power was limited, including fracture, cancer, and total mortality (131 vs 123 deaths; RH, 1.08; 95% CI, 0.84-1.38).Conclusions.—During an average follow-up of 4.1 years, treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease. The treatment did increase the rate of thromboembolic events and gallbladder disease. Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events, we do not recommend starting this treatment for the purpose of secondary prevention of CHD. However, given the favorable pattern of CHD events after several years of therapy, it could be appropriate for women already receiving this treatment to continue.

CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials

Abstract: Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. It was first published in 1996 and updated in 2001. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have endorsed the CONSORT statement. The statement facilitates critical appraisal and interpretation of RCTs. During the 2001 CONSORT revision, it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports. A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement. After an expert meeting in January 2007, the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement. This update improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias. This explanatory and elaboration document-intended to enhance the use, understanding, and dissemination of the CONSORT statement-has also been extensively revised. It presents the meaning and rationale for each new and updated checklist item providing examples of good reporting and, where possible, references to relevant empirical studies. Several examples of flow diagrams are included. The CONSORT 2010 Statement, this revised explanatory and elaboration document, and the associated website (www.consort-statement.org) should be helpful resources to improve reporting of randomised trials.