Cadmium exposure and cancer mortality in the Third National Health and Nutrition Examination Survey cohort.

Objective This study examined prospective data from the Third National Health and Nutrition Examination Survey (NHANES III) cohort to investigate the relationship between cadmium exposure and cancer mortality, and the specific cancers associated with cadmium exposure, in the general population. Methods Vital status and cause of death through 31 December 2006 were obtained by the National Center for Health Statistics for NHANES III participants. The cadmium concentration of spot urine samples was measured and corrected for urine creatinine (uCd). Weighted Cox proportional hazards regression with age as the time metric was applied to estimate sex-specific adjusted HRs (aHRs) of mortality associated with uCd for all cancers and the cancers responsible for the most deaths in the USA. Estimates were stratified by smoking history and adjusted for education, body mass index and race. Results uCd was associated with cancer mortality (aHR per twofold higher uCd (95% CI), men: 1.26 (1.07 to 1.48); women: 1.21 (1.04 to 1.42)). In men, mortality from lung cancer, pancreatic cancer and non-Hodgkin lymphoma was associated with uCd; an association with leukaemia mortality was suggested. In women, associations were suggested with mortality due to lung cancer, leukaemia, ovarian and uterine cancer, but evidence was weaker than in men. Conclusions Cadmium appears to be associated with overall cancer mortality in men and women, but the specific cancers associated differ between men and women, suggesting avenues for future research. Limitations of the study include the possibility of uncontrolled confounding by cigarette smoking or other factors, and the limited number of deaths due to some cancers

Cigarette Smoking Before and After Breast Cancer Diagnosis: Mortality From Breast Cancer and Smoking-Related Diseases

Cigarette smoking increases overall mortality, but it is not established whether smoking is associated with breast cancer prognosis

Post-diagnosis dietary factors and survival after invasive breast cancer.

Little is known about the effects of diet after breast cancer diagnosis on survival. We prospectively examined the relation between post-diagnosis dietary factors and breast cancer and all-cause survival in women with a history of invasive breast cancer diagnosed between 1987 and 1999 (at ages 20-79 years). Diet after breast cancer diagnosis was measured using a 126-item food frequency questionnaire. Among 4,441 women without a history of breast cancer recurrence prior to completing the questionnaire, 137 subsequently died from breast cancer within 7 years of enrollment. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for intake of macronutrients as well as selected micronutrients and food groups from Cox proportional hazards regression models. After adjustment for factors at diagnosis (age, state of residence, menopausal status, smoking, breast cancer stage, alcohol, history of hormone replacement therapy), interval between diagnosis and diet assessment, and at follow-up (energy intake, breast cancer treatment, body mass index, and physical activity), women in the highest compared to lowest quintile of intake of saturated fat and trans fat had a significantly higher risk of dying from any cause (HR = 1.41, 95% CI = 1.06-1.87, P trend = 0.03) for saturated fat; (HR = 1.78, 95% CI = 1.35-2.32, P trend = 0.01) for trans fat intake. Associations were similar, though did not achieve statistical significance, for breast cancer survival. This study suggests that lower intake of saturated and trans fat in the post-diagnosis diet is associated with improved survival after breast cancer diagnosis

BRAF Mutation Status and Survival after Colorectal Cancer Diagnosis According to Patient and Tumor Characteristics

BRAF mutations in colorectal cancer (CRC) are disproportionately observed in tumors exhibiting microsatellite instability (MSI), and are associated with other prognostic factors. The independent association between BRAF-mutation status and CRC survival, however, remains unclear

Genetic variation in prostaglandin synthesis and related pathways, NSAID use and colorectal cancer risk in the Colon Cancer Family Registry

Although use of non-steroidal anti-inflammatory drugs (NSAIDs) generally decreases colorectal cancer (CRC) risk, inherited genetic variation in inflammatory pathways may alter their potential as preventive agents. We investigated whether variation in prostaglandin synthesis and related pathways influences CRC risk in the Colon Cancer Family Registry by examining associations between 192 single nucleotide polymorphisms (SNPs) and two variable nucleotide tandem repeats (VNTRs) within 17 candidate genes and CRC risk. We further assessed interactions between these polymorphisms and NSAID use on CRC risk. Using a case-unaffected-sibling-control design, this study included 1621 primary invasive CRC cases and 2592 sibling controls among Caucasian men and women aged 18–90. After adjustment for multiple comparisons, two intronic SNPs were associated with rectal cancer risk: rs11571364 in ALOX12 [ORhet/hzv = 1.87, 95% confidence interval (CI) = 1.19–2.95, P = 0.03] and rs45525634 in PTGER2 (ORhet/hzv = 0.49, 95% CI = 0.29–0.82, P = 0.03). Additionally, there was an interaction between NSAID use and the intronic SNP rs2920421 in ALOX12 on risk of CRC (P = 0.03); among those with heterozygous genotypes, risk was reduced for current NSAID users compared with never or former users (ORhet = 0.60, 95% CI = 0.45–0.80), though not among those with homozygous wild-type or variant genotypes. The results of this study suggest that genetic variation in ALOX12 and PTGER2 may affect the risk of rectal cancer. In addition, this study suggests plausible interactions between NSAID use and variants in ALOX12 on CRC risk. These results may aid in the development of genetically targeted cancer prevention strategies with NSAIDs

Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer.

While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP-CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20-1.79, P=1.68x10−4). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92-1.18, P=0.49), 0.94 (95% CI: 0.84-1.05, P= 0.27), and 0.98 (95% CI: 0.85-1.12, P=0.75) respectively. A genetic risk score for 3-hydoxy-3-methylglutaryl-coenzyme A reductase (HMGCR) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR=0.69, 95% CI: 0.49-0.99, P=0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia. This article is protected by copyright. All rights reserved

Oral bisphosphonate use and colorectal cancer incidence in the Women's Health Initiative.

Bisphosphonates are widely prescribed to increase bone density in postmenopausal women with osteopenia or osteoporosis. Aminobisphosphonates have numerous anticancer properties and reduce bone metastases in cancer patients. Several studies, including the Women's Health Initiative (WHI), have found that use of oral bisphosphonates is associated with reduced risk of developing breast cancer, but less is known about associations with other common malignancies in women such as colorectal cancer (CRC). A few case-control and retrospective cohort studies have reported decreased risk of CRC among bisphosphonate users. In contrast, a prospective cohort study found no association. We evaluated the association between oral bisphosphonate use and CRC incidence in 156,826 postmenopausal women, ages 50 to 79 years, who participated in WHI clinical trials and observational study. A detailed health interview was conducted at baseline, and bisphosphonate use was ascertained from an inventory of regularly used medications at baseline and over follow-up. A total of 1931 women were diagnosed with incident invasive CRC during a median follow-up of 12 years. Alendronate was the most commonly used bisphosphonate, accounting for >90% of the total person-years of use. The association between oral bisphosphonate use and CRC risk did not reach statistical significance (hazard ratio [HR] from multivariable-adjusted models = 0.88; 95% confidence interval [CI] 0.72-1.07; p = 0.19). Furthermore, we did not observe greater risk reductions for women with longer duration of use. Uncontrolled confounding may explain why previous studies have observed an association