At the ends of chromosomes, telomeres are DNA-protein structures that protect the genome from damage, shorten progressively over time in most somatic tissues,¹ and are proposed physiological markers of aging.^2,3 Shorter leukocyte telomeres are correlated with older age, male sex, and other known risk factors for noncommunicable diseases^4-6 and are generally associated with higher risk for cardiovascular diseases,^7,8 type 2 diabetes,⁹ and nonvascular, non-neoplastic causes of mortality.⁸ Whether these associations are causal, however, is unknown. Telomere length has also been implicated in risk of cancer, but the direction and magnitude of the association is uncertain and contradictory across observational studies.^10-14 The uncertainty reflects the considerable difficulty of designing observational studies of telomere length and cancer incidence that are sufficiently robust to reverse causation, confounding, and measurement error.

Timothy Bishop and colleagues of the GenoMEL Consortium report a genome-wide association study for melanoma, identifying three new susceptibility loci. We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10−5 and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10−3: an SNP in ATM (rs1801516, overall P = 3.4 × 10−9), an SNP in MX2 (rs45430, P = 2.9 × 10−9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 × 10−10). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 × 10−7 under a fixed-effects model and P = 1.2 × 10−3 under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.

Matthew Law, Mark Iles and colleagues report the results of a large-scale genome-wide meta-analysis of cutaneous malignant melanoma. They confirm previously reported association signals and identify five new susceptibility loci, with associated variants mapping within putative melanocyte regulatory elements. Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 × 10−8), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology.

Purpose: To evaluate whether diabetes affects patterns of adjuvant chemotherapy use, toxic effects of chemotherapy, and breast cancer outcomes. Patients and Methods: By using the Surveillance, Epidemiology, and End Results–Medicare database, we identified patients aged 66 years or older who had stages I through III breast cancer that was diagnosed between 1992 and 2002. Multivariable regression analyses were performed to determine the effect of diabetes on use of chemotherapy, toxicities, and outcomes. The risks of all-cause mortality and breast cancer–specific (BCS) mortality were estimated with the Kaplan-Meier method. Results: Our cohort had 70,781 men and women, of whom 14,414 (20.36%) had diabetes. Among people who received chemotherapy (n = 11,826), 21.0% were diabetics. In this group, diabetics had lower odds of receiving anthracyclines (odds ratio [OR], 0.78; 95% CI, 0.71 to 0.87) and taxanes (OR, 0.86; 95% CI, 0.75 to 0.99). Diabetes was associated with increased odds of being hospitalized for any chemotherapy toxicity (OR, 1.38; 95% CI, 1.23 to 1.56), for infection or fever (OR, 1.43; 95% CI, 1.2 to 1.7), for neutropenia (OR, 1.22; 95% CI, 1.03 to 1.45), for anemia (OR, 1.24; 95% CI, 1.05 to 1.47), and for any cause (OR, 1.32; 95% CI, 1.19 to 1.46). Patients with diabetes had higher all-cause mortality (hazard ratio [HR], 1.35; 95% CI, 1.31 to 1.39). There was a significant interaction between diabetes and chemotherapy use for BCS mortality. Diabetic and nondiabetic patients who did not receive chemotherapy had similar BCS mortality, but diabetic patients who did receive chemotherapy had higher BCS mortality than nondiabetic patients (OR, 1.20; 95% CI, 1.07 to 1.35). Conclusion: In this observational, hypothesis-generating study, patients who have breast cancer and diabetes are at increased risk of chemotherapy-related toxicities compared with nondiabetic patients who are receiving chemotherapy and have higher all-cause mortality.

BACKGROUND: Few studies have examined the outcomes for Hispanic men with prostate carcinoma and incorporated socioeconomic factors in association with race/ethnicity in affecting survival, adjusting for factors on cancer stage, grade, comorbidity, and treatment.METHODS: We studied a population‐based cohort of 61,228 men diagnosed with local or regional stage prostate carcinoma at age 65 years or older between 1992 and 1999 in the 11 SEER (Surveillance, Epidemiology, and End Results) areas, identified from the SEER‐Medicare linked data with up to 11 years of followup.RESULTS: Low socioeconomic status was significantly associated with decreasing survival in all men with prostate carcinoma. Those living in the community with the lowest quartile of socioeconomic status were 31% more likely to die than those living in the highest quartile (hazard ratio [HR] of all‐cause mortality: 1.31; 95% confidence interval [CI]: 1.25–1.36) after adjustment for patient age, comorbidity, Gleason score, and treatment. The HR remained almost unchanged after controlling for race/ethnicity (HR: 1.32; 95% CI: 1.26–1.38). Compared with Caucasians, the risk of mortality in African American men was marginally significantly higher (HR: 1.06; 95% CI: 1.01–1.11) after controlling for education, and no longer significant after adjusting for poverty, income, or composite socioeconomic variable; the HR was lower for Hispanic men (HR: 0.80; 95% CI: 0.72–0.89) after adjustment for education and other socioeconomic variables.CONCLUSION: Racial disparity in survival among men with local or regional prostate carcinoma was largely explained by socioeconomic status and other factors. Lower socioeconomic status appeared to be one of the major barriers to achieving comparable outcomes for men with prostate carcinoma. Cancer 2006. © 2006 American Cancer Society.