Genetic variants in the MRPS30 region and postmenopausal breast cancer risk

Abstract{no abstract

Association between dietary inflammatory potential and breast cancer incidence and death: results from the Women\u27s Health Initiative

BACKGROUND: Diet modulates inflammation and inflammatory markers have been associated with cancer outcomes. In the Women\u27s Health Initiative, we investigated associations between a dietary inflammatory index (DII) and invasive breast cancer incidence and death. METHODS: The DII was calculated from a baseline food frequency questionnaire in 122 788 postmenopausal women, enrolled from 1993 to 1998 with no prior cancer, and followed until 29 August 2014. With median follow-up of 16.02 years, there were 7495 breast cancer cases and 667 breast cancer deaths. We used Cox regression to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (95% CIs) by DII quintiles (Q) for incidence of overall breast cancer, breast cancer subtypes, and deaths from breast cancer. The lowest quintile (representing the most anti-inflammatory diet) was the reference. RESULTS: The DII was not associated with incidence of overall breast cancer (HRQ5vsQ1, 0.99; 95% CI, 0.91-1.07; Ptrend=0.83 for overall breast cancer). In a full cohort analysis, a higher risk of death from breast cancer was associated with consumption of more pro-inflammatory diets at baseline, after controlling for multiple potential confounders (HRQ5vsQ1, 1.33; 95% CI, 1.01-1.76; Ptrend=0.03). CONCLUSIONS: Future studies are needed to examine the inflammatory potential of post-diagnosis diet given the suggestion from the current study that dietary inflammatory potential before diagnosis is related to breast cancer death

Placebo Adherence, Clinical Outcomes, and Mortality in the Womenʼs Health Initiative Randomized Hormone Therapy Trials

Medication adherence may be a proxy for healthy behaviors and other factors that affect outcomes. Prior studies of the association between placebo adherence and health outcomes have been limited primarily to men enrolled in clinical trials and cardiovascular disease outcomes. We examined associations between adherence to placebo and the risk of fracture, coronary heart disease, cancer, and all-cause mortality in the two Women’s Health Initiative (WHI) hormone therapy randomized trials

Dietary vitamin D and calcium intake and mammographic density in postmenopausal women

Dietary intake of vitamin D and calcium may be related to risk of breast cancer, possibly by affecting mammographic density. However, the few studies that have evaluated the association between these nutrients and mammographic density in postmenopausal women have had inconsistent results

Hematopoietic prostaglandin D synthase (HPGDS): A high stability, Val187Ile isoenzyme common among African Americans and its relationship to risk for colorectal cancer

Intestinal tumors in ApcMin/+ mice are suppressed by over-production of HPGDS, which is a glutathione transferase that forms prostaglandin D2 (PGD2). We characterized naturally occurring HPGDS isoenzymes, to see if HPGDS variation is associated with human colorectal cancer risk. We used DNA heteroduplex analysis and sequencing to identify HPGDS variants among healthy individuals. HPGDS isoenzymes were produced in bacteria, and their catalytic activities were tested. To determine in vivo effects, we conducted pooled case-control analyses to assess whether there is an association of the isoenzyme with colorectal cancer. Roughly 8% of African Americans and 2% of Caucasians had a highly stable Val187lle isoenzyme (with isoleucine instead of valine at position 187). At 37 °C, the wild-type enzyme lost 15% of its activity in one hour, whereas the Val187Ile form remained >95% active. At 50 °C, the half life of native HPGDS was 9 minutes, compared to 42 minutes for Val187Ile. The odds ratio for colorectal cancer among African Americans with Val187Ile was 1.10 (95% CI, 0.75–1.62; 533 cases, 795 controls). Thus, the Val187Ile HPGDS isoenzyme common among African Americans is not associated with colorectal cancer risk. Other approaches will be needed to establish a role for HPGDS in occurrence of human intestinal tumors, as indicated by a mouse model

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc

Severity of comorbid conditions and early-stage breast cancer therapy: linked SEER-Medicare data from 1993 to 2005.

Comorbidity burden has been suggested as influencing early-stage breast cancer therapy but previous studies have not considered the severity of these comorbidities. Therefore, we examined the influence of comorbidity severity by age and race/ethnicity on early-stage breast cancer treatment over time. We used linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data to determine whether comorbidity severity influences receipt of definitive and preferred early-stage breast cancer treatment and explains racial/ethnic and age disparities in receiving such therapy. Definitive surgical therapy was defined as any primary surgery other than breast conserving surgery (BCS) without radiation therapy (RT). Preferred surgical therapy was defined as BCS plus RT. Comorbidities were defined as either "unstable" (life threatening or difficult to control) or "stable" (less serious but with potential to influence daily activity). Surgical treatment trends from 1993 to 2005 were analyzed in regression models adjusting for comorbidity burden, age, and race/ethnicity in 93,596 elderly female Medicare beneficiaries with stage 1-2 invasive breast cancer. Receipt of BCS alone (compared with any definitive surgical therapy) was independently associated with neighborhood socioeconomic status, unmarried status (OR [odds ratio] 1.18, 95% CI: 1.12-1.23), tumor size (OR 0.78, 95% CI: 0.69-0.87 for tumors ≥4 cm vs. <2 cm), tumor grade (OR = 0.89, 0.88, and 0.81 for grades 2-4 vs. 1, respectively), stable comorbidities (OR = 0.76, 0.71, and 0.72 for 1, 2, and 3 vs. 0 stable comorbidities, respectively), and unstable comorbidities (OR 1.20, 95% CI: 1.14-1.28). Black women were 4-5% more likely to receive suboptimal therapy (BCS alone), even after adjusting for all available patient, tumor, and regional characteristics. Black race/ethnicity was associated with higher probability of receiving suboptimal treatment, independent of comorbidities, although we do not know whether this effect was due to clinicians' failure to offer RT or patients' failure to accept it

Severity of comorbid conditions and early-stage breast cancer therapy: linked SEER-Medicare data from 1993 to 2005.

Comorbidity burden has been suggested as influencing early-stage breast cancer therapy but previous studies have not considered the severity of these comorbidities. Therefore, we examined the influence of comorbidity severity by age and race/ethnicity on early-stage breast cancer treatment over time. We used linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data to determine whether comorbidity severity influences receipt of definitive and preferred early-stage breast cancer treatment and explains racial/ethnic and age disparities in receiving such therapy. Definitive surgical therapy was defined as any primary surgery other than breast conserving surgery (BCS) without radiation therapy (RT). Preferred surgical therapy was defined as BCS plus RT. Comorbidities were defined as either "unstable" (life threatening or difficult to control) or "stable" (less serious but with potential to influence daily activity). Surgical treatment trends from 1993 to 2005 were analyzed in regression models adjusting for comorbidity burden, age, and race/ethnicity in 93,596 elderly female Medicare beneficiaries with stage 1-2 invasive breast cancer. Receipt of BCS alone (compared with any definitive surgical therapy) was independently associated with neighborhood socioeconomic status, unmarried status (OR [odds ratio] 1.18, 95% CI: 1.12-1.23), tumor size (OR 0.78, 95% CI: 0.69-0.87 for tumors ≥4 cm vs. <2 cm), tumor grade (OR = 0.89, 0.88, and 0.81 for grades 2-4 vs. 1, respectively), stable comorbidities (OR = 0.76, 0.71, and 0.72 for 1, 2, and 3 vs. 0 stable comorbidities, respectively), and unstable comorbidities (OR 1.20, 95% CI: 1.14-1.28). Black women were 4-5% more likely to receive suboptimal therapy (BCS alone), even after adjusting for all available patient, tumor, and regional characteristics. Black race/ethnicity was associated with higher probability of receiving suboptimal treatment, independent of comorbidities, although we do not know whether this effect was due to clinicians' failure to offer RT or patients' failure to accept it