We conducted a genome-wide association study (GWAS) of breast cancer by genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer and confirmed this association in 1,776 affected individuals and 2,072 controls from three additional studies. Across the four studies, the association with all four SNPs was highly statistically significant (P(trend) for the most strongly associated SNP (rs1219648) = 1.1 x 10(-10); population attributable risk = 16%). Four SNPs at other loci most strongly associated with breast cancer in the initial GWAS were not associated in the replication studies. Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci.

Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 x 10(-13); heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13-1.41; homozygote OR: 1.58, 95% c.i.: 1.40-1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 x 10(-11); rs6983267 P = 6.62 x 10(-10)). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%).

Objectives To quantify trends in pediatric computed tomography (CT) use and associated radiation exposure and cancer risk. Design Retrospective observational study. Setting Seven US healthcare systems. Participants CT use was evaluated in children <15 years from 1996-2010, including 4,857,736 child-years of observation. Radiation doses were calculated for 744 CT scans performed between 2001-2011. Outcome Measures Rates of CT use, organ and effective doses, and projected lifetime attributable cancer risks. Results CT use doubled in children <5 years and tripled in children 5-14 between 1996-2005, stabilized until 2007, then declined. Effective doses varied from 0.03-69.2mSv per scan. An effective dose of ≥20mSv was delivered by 14-25% of abdomen/pelvis CTs, 6-14% of spine CTs, and 3-8% of chest CTs. Projected lifetime attributable risks of solid cancer were higher in younger patients and girls, and for abdomen/pelvis and spine CTs. In girls, a radiation-induced solid cancer is projected to result from every 300-390 abdomen/pelvis CTs, 330-480 chest CTs, and 270-800 spine CTs, depending on age. Leukemia risk was highest for head CTs in children <5 at 1.9/10,000. Nationally, 4 million pediatric CTs of the head, abdomen/pelvis, chest, or spine performed each year are projected to cause 4870 future cancers. Reducing the highest 25% of doses to the median might prevent 43% of these cancers. Conclusions Increased use of pediatric CT combined with wide variability in radiation doses has resulted in many children receiving a high-dose examination. Dose-reduction strategies targeted to the highest quartile of doses could dramatically reduce the number of radiation-induced cancers.

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Patients with large-vessel peripheral arterial disease have a high risk of death from cardiovascular causes.