Genetic variation in C-reactive protein in relation to colon and rectal cancer risk and survival

C-reactive protein (CRP), a biomarker of inflammation, has been shown to be influenced by genetic variation in the CRP gene. In this study, we test the hypothesis that genetic variation in CRP influences both the risk of developing colon and rectal cancer and survival. Two population-based studies of colon cancer (n = 1,574 cases, 1,970 controls) and rectal (n = 791 cases, 999 controls) were conducted. We evaluated four CRP tagSNPs: rs1205 (G > A, 3' UTR); rs1417938 (T > A, intron); rs1800947 (G > C, L184L); and rs3093075 (C > A, 3' flanking). The CRP rs1205 AA genotype was associated with an increased risk of colon cancer (OR 1.3, 95%CI 1.1-1.7), whereas the rs3093075 A allele was associated with a reduced risk of rectal cancer (OR 0.7, 95%CI 0.5-0.9). The strongest association for the rs1205 polymorphism and colon cancer was observed among those with KRAS2 mutations (OR 1.5, 95%CI 1.1-2.0). The CRP rs1205 AA genotype also was associated with an increased risk of CIMP+ rectal tumors (OR 2.5, 95%CI 1.2-5.3); conversely, the rs1417938 A allele was associated with a reduced risk of CIMP+ rectal tumors (OR 0.5, 95%CI 0.3-0.9). We observed interactions between CRP rs1800947 and BMI and family history of CRC in modifying risk of both colon and rectal cancer. These data suggest that genetic variation in the CRP gene influences risk of both colon and rectal cancer development.     

Vegetable intake is associated with reduced breast cancer recurrence in tamoxifen users: a secondary analysis from the Women’s Healthy Eating and Living Study

The protective effect of vegetables on the risk of breast cancer recurrence is uncertain. We sought to evaluate the association between breast cancer recurrence and vegetable intake including analyses stratified on tamoxifen use. Experimental evidence of anti-carcinogenic activity of phytochemicals in cruciferous vegetables in combination with tamoxifen led to specific evaluation of this class of vegetables as well. To assess the association between vegetable intake and breast cancer recurrence, vegetable intake from repeat 24-h dietary recalls were examined as a secondary analysis of 3,080 breast cancer survivors enrolled in the Women’s Healthy Eating and Living (WHEL) Study. At the time of enrollment women were, on average, 23.5 months post-diagnosis. The hazard of recurrence, controlling for relevant and significant clinical and demographic variables, with vegetable intake was assessed overall and separately for women taking tamoxifen. WHEL participants reported mean baseline intakes ( [`(\text x)]{\bar{\text {x}}}, SE) of 3.1 ± 0.05 and 0.5 ± 0.02 servings/day of total and cruciferous vegetables, respectively. Baseline vegetable intake in the highest as compared to lowest tertiles was associated with an overall lower adjusted hazard ratios (HR) for recurrence of 0.69, 95% CI 0.55–0.87. Among women taking tamoxifen, the HRs were 0.56, 95% CI 0.41–0.77 for total vegetables and 0.65, 95% CI 0.47–0.89 for cruciferous vegetable intake. The hazard in women using tamoxifen who reported cruciferous vegetable intake above the median and who were within the highest tertile of total vegetable intake was HR 0.48; 95% CI 0.32–0.70. This secondary analysis in over 3,000 breast cancer survivors suggests that baseline vegetable intake may be associated with a reduction in the risk of breast cancer recurrent or new events particularly for those using tamoxifen. Such associations should be explored further as the possibility that vegetable intake is simply a surrogate for other health-promoting behaviors cannot be ruled out.     

Update in the methodology of the chronic stress paradigm: internal control matters

To date, the reliability of induction of a depressive-like state using chronic stress models is confronted by many methodological limitations. We believe that the modifications to the stress paradigm in mice proposed herein allow some of these limitations to be overcome. Here, we discuss a variant of the standard stress paradigm, which results in anhedonia. This anhedonic state was defined by a decrease in sucrose preference that was not exhibited by all animals. As such, we propose the use of non-anhedonic, stressed mice as an internal control in experimental mouse models of depression. The application of an internal control for the effects of stress, along with optimized behavioural testing, can enable the analysis of biological correlates of stress-induced anhedonia versus the consequences of stress alone in a chronic-stress depression model. This is illustrated, for instance, by distinct physiological and molecular profiles in anhedonic and non-anhedonic groups subjected to stress. These results argue for the use of a subgroup of individuals who are negative for the induction of a depressive phenotype during experimental paradigms of depression as an internal control, for more refined modeling of this disorder in animals.     

Dietary intake of folate and co-factors in folate metabolism, <Emphasis Type="Italic">MTHFR</Emphasis> polymorphisms,and reduced rectal cancer

Little is known about the contribution of polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and the folate metabolism pathway in rectal cancer alone. Data were from participants in a case–control study conducted in Northern California and Utah (751 cases and 979 controls). We examined independent associations and interactions of folate, B vitamins, methionine, alcohol, and MTHFR polymorphisms (MTHFR C677T and A1298C) with rectal cancer. Dietary folate intake was associated with a reduction in rectal cancer OR 0.66, 95% CI 0.48–0.92 (>475 mcg day compared to < = 322 mcg) as was a combination of nutrient intakes contributing to higher methyl donor status (OR 0.79, 95% CI 0.66–0.95). Risk was reduced among women with the 677 TT genotype (OR 0.54, 95% CI 0.30–0.9), but not men (OR 1.11, 95% CI 0.70–1.76) and with the 1298 CC genotype in combined gender analysis (OR 0.67, 95% CI 0.46–0.98). These data are consistent with a protective effect of increasing dietary folate against rectal cancer and suggest a protective role of the MTHFR 677 TT genotype in women and 1298 CC in men and women. Folate intake, low methyl donor status, and MTHFR polymorphisms may play independent roles in the etiology of rectal cancer.     

Smoking and survival after breast cancer diagnosis: a prospective observational study and systematic review

The association of smoking with outcomes following breast cancer prognosis is not well understood. In a cohort study called Life After Cancer Epidemiology (LACE), 2,265 women diagnosed with breast cancer were followed for a median of 12?years. We used multivariable proportional-hazards models to determine whether smoking, assessed approximately two years post-diagnosis, was associated with risk of death among these women. We also undertook a systematic review of all cohort studies to date that have examined the association between smoking and breast cancer mortality. Compared with never smokers, women who were current smokers had a twofold higher rate of dying from breast cancer [hazard ratio (HR)?=?2.01, 95?% confidence interval (CI) 1.27?C3.18] and an approximately fourfold higher rate of dying from competing (non-breast cancer) causes (HR?=?3.84, 95?% CI 2.50?C5.89). Among seven studies that met the inclusion criteria in the systematic review, three studies and our own reported significantly increased risk of breast cancer death with current smoking. We found little evidence of an association between former smoking and breast cancer mortality (HR?=?1.24, 95?% CI 0.94?C1.64). Consistent with findings from our prospective observational study, the systematic review of seven additional studies indicates positive association of current smoking with breast cancer mortality, but weak association with former smoking. Women who smoke following breast cancer diagnosis and treatment are at higher risk of death both from breast cancer and other causes.