Highlights of This Issue

In a Seattle-based cohort of patients diagnosed with clinically localized prostate cancer, patients who reported vigorous physical activity at least once per week during the year before diagnosis were less likely to progress to metastatic–lethal prostate cancer compared to those who had less frequent physical activity (adjusted hazard ratio = 0.63, p-value = 0.029). Dai and colleagues identified a differentially methylated region (associated with both physical activity and metastatic–lethal progression) in the promoter region of CRACR2A, a gene encoding a calcium binding protein involved in innate immune response and neutrophil degranulation.

Previous studies investigating associations of breast cancer with dietary intakes of lignans, phytoestrogens prevalent in whole grains, vegetables, fruits, and seeds, have been inconsistent. Some inconsistency may be related to genetic variation in lignan metabolism. Chang and colleagues investigated the impact of polymorphisms in 29 genes involved in steroid hormone and xenobiotic metabolism on lignan excretion after a flaxseed intervention in African American and European American healthy postmenopausal women. They identified several SNPs associated with lignan excretion, particularly among African American women. Future dietary interventions to reduce breast cancer burden may benefit from incorporating information on genetic variation in metabolism.

Folic acid and vitamin-B12 play key roles in one-carbon metabolism, which has been implicated in the development of cancer. Given current considerations on folic acid fortification globally, it is essential to evaluate potential adverse effects. The aim of this study was to conduct secondary analyses on cancer incidence within the B-PROOF study, a randomized controlled trial on vitamin-B12 and folic acid supplementation on fracture risk. Oliai Araghi and colleagues found that B-vitamin supplementation increased the risk of cancer, and colorectal cancer in particular. This suggests that folic acid and vitamin-B12 supplementation should be limited to patients with proven deficiencies.

Decreasing sequencing costs make population genetic screening increasingly feasible. However, the substantial infrastructure needs require thoughtful consideration of screening eligibility guidelines, which range from full-population testing to testing only those with strong personal or family histories. This study utilized a clinical risk prediction tool (BRCAPRO) to calculate BRCA1/2 carrier-probabilities for a population of Ashkenazi-Jewish women whose mutation status was known. Best and colleagues found that identifying 90% of known BRCA1/2 founder-mutations required testing only 60% of Ashkenazi-Jewish women (carrier-probability>0.56%). An estimated 0.7-1.1 million U.S. Ashkenazi-Jewish women might avoid unnecessary mutation-testing. Low carrier-probability thresholds (<1%) could maximize the public-health benefit of BRCA1/2 screening.