American Cancer Society

About: American Cancer Society is a nonprofit organization based out in Atlanta, Georgia, United States. It is known for research contribution in the topics: Cancer & Population. The organization has 1339 authors who have published 3700 publications receiving 688166 citations. The organization is also known as: American Cancer Society, ACS & American Society for the Control of Cancer.

Gimme 5 Fruit and Vegetables for Fun and Health: Process Evaluation:

Abstract: Gimme 5 (Georgia) was a school-based nutrition education effectiveness trial to help fourth- and fifth-grade students eat more fruit, 100% juice, and vegetables (FJV). Process evaluation assessed fidelity of implementation, reach, and use of intervention materials and environmental mediators: teacher training, curriculum delivery, participation in family activities, attendance at evening point-of-purchase grocery store activities, and availability and accessibility of FJV at home. Approximately half of the curriculum activities were implemented in fourth and fifth grades. The lowest proportion completed were those most pertinent to behavior change. Eighty-seven percent of parents reported participating in homework activities with their fourth grader, 66% with fifth graders. Sixty-five percent of parents reported viewing a video with their child in both grades. Ten percent attended evening point-of-purchase grocery store activities. The low level of implementation and modest level of participation in famil...

Family History and Risk of Fatal Prostate Cancer

Abstract: To examine the relation between fatal prostate cancer and family history of prostate cancer in a first-degree relative, we analyzed data from a prospective mortality study of 481,011 men with no history of cancer at enrollment in 1982. During 9 years of follow-up, 1,922 deaths from prostate cancer occurred. Results from Cox proportional hazard models showed that family history of prostate cancer was related to fatal prostate cancer [rate ratio (RR) = 1.60; 95% confidence interval (CI) = 1.31-1.97]; men with two or more affected relatives had a greater than threefold increase in risk (RR = 3.19; 95% CI = 1.51-6.71). Men whose relatives were diagnosed with prostate cancer before age 65 years (RR = 2.03; 95% CI = 1.33-3.09) had a greater effect of family history than men whose relatives were diagnosed at older ages (RR = 1.50; 95% CI = 1.17-1.91). Rate ratios did not increase with decreasing age of the study participants. The 60% increase in risk for men with at least one affected relative is lower than that reported in previous studies.

Variation in KLK genes, prostate-specific antigen and risk of prostate cancer

Abstract: Genome-wide association studies have identified SNPs associated with prostate cancer. Recently, SNPs in KLK3 were related to prostate cancer risk in a genome-wide association study (GWAS; 1,854 cases)1 and two candidate gene investigations (596 and 209 cases, respectively)2,3, raising the possibility that this gene and its encoded protein PSA (prostate specific antigen; kallikrein-related peptidase), which is widely-used as a biomarker for prostate cancer detection, are etiologically related to this disease. Understanding the contribution of common genetic variation in KLK3 to prostate cancer risk is daunting because SNPs in KLK3 are determinants of serum PSA concentrations1,2,4, and thus, observed risk relationships could be due to differential identification of cases, in settings where PSA is used in screening or clinical diagnosis of this disease. Therefore, we evaluated the association of 24 tagSNPs in the KLK region (including KLK3 and nearby genes KLK1, KLK2, and KLK15, chromosome 19: 56022744–56073589) and prostate cancer risk in 1,172 prostate cancer cases and 1,157 PSA screened controls in men of European ancestry from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial5,6, in which serum PSA was used in screening for this disease. We also examined the prostate cancer risk relationship for 12 of these tagSNPs in the KLK3 region (chromosome 19: 56031744–56063231) in four independent studies including 4,020 prostate cancer cases and 4,028 controls (American Cancer Society Cancer Prevention Study II, the Health Professionals Follow-up Study, the CeRePP French Prostate Case-Control Study, and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study)6, as a component of the Cancer Genetic Markers of Susceptibility (CGEMS)-GWAS6 (http://cgems.cancer.gov; Supplementary Methods). None of the 24 KLK-region tagSNPs showed strong evidence for association with prostate cancer in PLCO (Table 1: Cases vs Controls in PLCO) and none of the 12 KLK3-region SNPs was significant in the CGEMS combined analyses (Table 1: Cases vs Controls in CGEMS combined). No substantial differences in risk were noted by disease aggressiveness (Supplement Table 1). Two tagSNPs (rs1058205 and rs2735839), located in the 3′ untranslated region of KLK3, in high linkage disequilibrium (LD; r2=0.8; Figure 1), along with four variants 8–23 kb upstream of the gene (rs2659056, rs2569729, rs266849, and rs266870) and several variants about 7 kb downstream (rs1506684 and rs2569739, in high LD, r2=1.0), were associated with strong differentials in serum PSA concentrations (e.g., rs2735839, p trend=4.1×10−9; Table 1, Adjusted Mean PSA Level, and Figure 1-Panel A). However, when these SNPs were simultaneously included in the multivariate model, associations remained for rs2735839, but others were no longer significantly associated with PSA concentrations. Figure 1 Associations of tagSNPs in the KLK region with PSA concentrations and prostate cancer risk in the PLCO Trial Table 1 Associations of tagSNPs in the KLK region with prostate cancer risk and PSA concentrations in the PLCO Cancer Screening Trial and with prostate cancer in the combined CGEMS follow-up study. Eeles et al 1 reported strong associations between three KLK3 SNPs (p-values for stage 1 were 1.2×10−7, 1.0×10−16 and 2.4×10−20 for rs2659056, rs266849, and rs2735839) and prostate cancer, in a GWAS, where controls were selected by design for low PSA (<0.5 ng/ml) and no limitations were placed on case-group PSA values. The replications in non-PSA selected groups showed attenuated associations (p-values for stage 2 were 0.424, 0.228 and 0.0002, respectively). Pal et al 2 also reported a strong association of prostate cancer with KLK3 variants, where control subjects were also preferentially selected by PSA levels (< 2.5 ng/ml). When we preferentially limited the men in the control group in the PLCO Trial GWAS to those with PSA <0.5 ng/ml, as an exercise, we show prostate cancer risk associations (Figure 1-Panel B [▴] and Supplement Table 2) greater than 5-fold for some genotypes (rs1058205, OR=0.19, 95%CI=0.10–0.36, p=0.000015), whereas the same SNPs showed no clear association when the full control group was employed (Figure 1-Panel B [●] and Table 1). Furthermore, modest KLK3 associations with prostate cancer risk observed in our full case-control series and in other studies where controls are not selected by design for PSA level3 may still be related to PSA-based case ascertainment, because PSA is widely used as a clinical aid in selecting men for biopsy for suspect prostate cancer. In PLCO, KLK SNPs were also not associated with prostate cancer when only cases and controls with high PSA levels or only cases and controls with low PSA levels were compared (Supplement Table 3). Thus, the observed associations between the KLK SNPs and prostate cancer risk in earlier studies4,5,3 and in our exercise in PLCO may be due to selection for PSA differentials and not causally related to underlying disease risk. PSA is a serine protease, functioning in the liquefaction of seminal coagulum7; consistent with our data, Pal et al2 showed serum PSA associations with rs266849 and rs1058205, and Cramer et al4 showed that two SNPs in the 5′ region of KLK3 are related to increased KLK3 promoter activity and serum PSA level. In our study, the association with PSA was strongest with rs2735839, which is highly correlated with rs1058205 (r2=0.8); associations observed with the other SNPs in our study appeared to be largely driven by their linkage disequilibrium with rs2735839. Sliding window haplotype analysis (Supplement Figure 1) and close inspection of the most strongly associated haplotype window (Supplementary Table 4) suggested that additional unmeasured risk variant(s) may influence PSA concentrations. PSA is an early marker predictive for the presence of prostate cancer and its use has contributed to the near doubling of diagnosed cases over the past two decades in countries where use is common8. While trials are underway to determine whether screening with PSA reduces prostate cancer mortality5,9, it is apparent that many men are diagnosed with clinically indolent cancer on the basis of PSA screening; the over-detection rate is estimated to range from 18 to 56%9,10. In addition, the majority of men with an elevated PSA have a negative biopsy11. In our study, KLK3 variant status was related to PSA test-positivity in control men (Supplementary Table 5). While we show that KLK3 SNPs are not risk factors highly correlated with prostate cancer per se, a combination of KLK3 SNP and serum PSA monitoring, possibly including a broader spectrum of protein and DNA tests12, is a potential tool for advancement in prostate cancer early detection. In conclusion, SNPs in the KLK3 region were not associated strongly with prostate cancer in large series of cases and controls, where controls are not selected by design for low PSA and even the modest KLK3-prostate cancer risk associations observed in non-selected populations may be due to PSA-directed differential identification of prostate cancer cases with particular KLK3-PSA profiles.

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Abstract: Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.