Prediction of breast cancer risk based on profiling with common genetic variants

BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

A randomized trial to assess the potential of different beverages to affect hydration status: development of a beverage hydration index

Background: The identification of beverages that promote longer- term fluid retention and maintenance of fluid balance is of real clinical and practical benefit in situations in which free access to fluids is limited or when frequent breaks for urination are not desirable. The postingestion diuretic response is likely to be influenced by several beverage characteristics, including the volume ingested, energy den- sity, electrolyte content, and the presence of diuretic agents. Objective: This study investigated the effects of 13 different com- monly consumed drinks on urine output and fluid balance when ingested in a euhydrated state, with a view to establishing a beverage hydration index (BHI), i.e., the volume of urine produced after drinking expressed relative to a standard treatment (still water) for each beverage. Design: Each subject (n = 72, euhydrated and fasted male subjects) ingested 1 L still water or 1 of 3 other commercially available beverages over a period of 30 min. Urine output was then collected for the subsequent 4 h. The BHI was corrected for the water content of drinks and was calculated as the amount of water retained at 2 h after ingestion relative to that observed after the ingestion of still water. Results: Total urine masses (mean 6 SD) over 4 h were smaller than the still-water control (1337 6 330 g) after an oral rehydration solution (ORS) (1038 6 333 g, P , 0.001), full-fat milk (1052 6 267 g, P , 0.001), and skimmed milk (1049 6 334 g, P , 0.001). Cumulative urine output at 4 h after ingestion of cola, diet cola, hot tea, iced tea, coffee, lager, orange juice, sparkling water, and a sports drink were not different from the response to water ingestion. The mean BHI at 2 h was 1.54 6 0.74 for the ORS, 1.50 6 0.58 for full- fat milk, and 1.58 6 0.60 for skimmed milk. Conclusions: BHI may be a useful measure to identify the short- term hydration potential of different beverages when ingested in a euhydrated state.