Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Input: Consider Input: Context: Women with a family history of breast cancer face considerable uncertainty about whether to pursue standard screening, intensive screening, or prophylactic surgery. Accurate and individualized risk-estimation approaches may help these women make more informed decisions. Although highly penetrant genetic variants have been associated with familial breast cancer (FBC) risk, many individuals do not carry these variants, and many carriers never develop breast cancer. Common risk variants have a relatively modest effect on risk and show limited potential for predicting FBC development. As an alternative, we hypothesized that additional genomic data types, such as gene-expression levels, which can reflect genetic and epigenetic variation, could contribute to classifying a person's risk status. Specifically, we aimed to identify common patterns in gene-expression levels across individuals who develop FBC.", 'We profiled peripheral blood mononuclear cells from women with a family history of breast cancer (with or without a germline BRCA1/2 variant) and from controls. We used the support vector machines algorithm to differentiate between patients who developed FBC and those who did not. Our study used two independent datasets, a training set of 124 women from Utah (USA) and an external validation (test) set from Ontario (Canada) of 73 women (197 total). We controlled for expression variation associated with clinical, demographic, and treatment variables as well as lymphocyte markers.', 'Our multigene biomarker provided accurate, individual-level estimates of FBC occurrence for the Utah cohort (AUC = 0.76 [0.67-84]) . Even at their lower confidence bounds, these accuracy estimates meet or exceed estimates from alternative approaches. Our Ontario cohort resulted in similarly high levels of accuracy (AUC = 0.73 [0.59-0.86]), thus providing external validation of our findings. Individuals deemed to have "high" risk by our model would have an estimated 2.4 times greater odds of developing familial breast cancer than individuals deemed to have "low" risk.
Answer: Together, these findings suggest that gene-expression levels in peripheral blood cells reflect genomic variation associated with breast cancer risk and that such data have potential to be used as a non-invasive biomarker for familial breast cancer risk.

Output: Do gene-expression patterns in peripheral blood classify familial breast cancer susceptibility?


Input: Consider Input: Context: Long-QT syndrome (LQTS), a cardiac arrhythmia disorder with variable phenotype, often results in devastating outcomes, including sudden cardiac death. Variable expression, independently from the primary disease-causing mutation, can partly be explained by genetic modifiers. This study investigates variants in a known LQTS-causative gene, AKAP9, for potential LQTS-type 1-modifying effects.', "Members of a South African LQTS-type 1 founder population (181 noncarriers and 168 mutation carriers) carrying the identical-by-descent KCNQ1 p.Ala341Val (A341V) mutation were evaluated for modifying effects of AKAP9 variants on heart rate-corrected QT interval (QTc), cardiac events, and disease severity. Tag single nucleotide polymorphisms in AKAP9 rs11772585, rs7808587, rs2282972, and rs2961024 (order, 5'-3'positive strand) were genotyped. Associations between phenotypic traits and alleles, genotypes, and haplotypes were statistically assessed, adjusting for the degree of relatedness and confounding variables. The rs2961024 GG genotype, always represented by CGCG haplotype homozygotes, revealed an age-dependent heart rate-corrected QT interval increase (1% per additional 10 years) irrespective of A341V mutation status (P=0.006). The rs11772585 T allele, found uniquely in the TACT haplotype, more than doubled (218%) the risk of cardiac events (P=0.002) in the presence of A341V; additionally, it increased disease severity (P=0.025). The rs7808587 GG genotype was associated with a 74% increase in cardiac event risk (P=0.046), whereas the rs2282972 T allele, predominantly represented by the CATT haplotype, decreased risk by 53% (P=0.001).
Answer: AKAP9 has been identified as an LQTS-type 1-modifying gene. Variants investigated altered heart rate-corrected QT interval irrespective of mutation status, as well as cardiac event risk, and disease severity, in mutation carriers.

Output: Is aKAP9 a genetic modifier of congenital long-QT syndrome type 1?


Input: Consider Input: Context: Cardiac surgery produces a proinflammatory response characterized by cytokine production. Proinflammatory cytokines such as interleukin 6 (IL-6) may contribute to morbidity and mortality after cardiopulmonary bypass (CPB). Elderly patients undergoing CPB are at increased risk of morbidity and mortality. We hypothesized that patients aged >70 y produce more IL-6 during CPB.', 'Twenty-three patients (ages 23-80) undergoing cardiac surgery had blood sampled from the ascending aorta and coronary sinus on initial cannulation for bypass, at 30 min of aortic cross-clamp time, on release of the aortic cross-clamp, and at 20 min after reperfusion. Group 1 patients (n = 8) were aged <60 y, group 2 patients (n = 7) were aged between 60 and 70 y, and group 3 patients (n = 8) were aged >70 y. Plasma levels of tumor necrosis factor-alpha, IL-1, and IL-6 were analyzed.', 'The three groups did not differ with respect to preoperative ejection fraction, New York Heart Association classification, mean aortic cross-clamp time, or mean CPB time. IL-6 levels rose throughout myocardial ischemia and reperfusion in all three age groups. The increase in IL-6 during ischemia and reperfusion in the age group >70 was greater than the increase in younger patients. IL-6 was similar in the coronary sinus and the ascending aorta.
Answer: These data suggest that patients aged >70 y undergoing cardiac operations generate more IL-6 during CPB. The increased circulating IL-6 in elderly patients may incite a proinflammatory state that could subsequently underlie the associated higher mortality and morbidity of these procedures in elderly patients.


Output: Does interleukin 6 production during cardiac surgery correlate with increasing age?