Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study.

BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. CONCLUSIONS: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior

Trajectory of overall health from self-report and factors contributing to health declines among cancer survivors

PURPOSE: This study aims to quantify trajectories of overall health pre- and post-diagnosis of cancer, trajectories of overall health among cancer-free individuals, and factors affecting overall health status. METHODS: Overall health status, derived from self-rated health report, of Atherosclerosis Risk in Communities (ARIC) cohort participants diagnosed with incident cancer (lung (N=400), breast (N=522), prostate (N=615), colorectal (N=303)), and cancer-free participants (N=11,634) over 19 years was examined. Overall health was evaluated in two ways: 1) overall health was assessed until death or follow-up year 19 (survivorship model) and 2) same as survivorship model except that a SRH value of zero was used for assessments after death to follow-up year 19 (cohort model). Mean overall health at discrete times was used to generate overall health trajectories. Differences in repeated measures of overall health were assessed using linear growth models. RESULTS: Overall health trajectories declined dramatically within one-year of cancer diagnosis. Lung, breast, and colorectal cancer were associated with a significant decreased overall health score (β) compared to the cancer-free group (survivorship model: lung −7.00, breast −3.97, colorectal −2.12; cohort model: lung −7.63, breast −5.07, colorectal −2.30). Other predictors of decreased overall health score included low education, diabetes, cardiovascular disease, and age. CONCLUSIONS: All incident cancer groups had declines in overall health during the first year post-diagnosis, which could be due to cancer diagnosis or intensive treatments. Targeting factors related to overall health declines could improve health outcomes for cancer patients

Correlation Between Obesity and High Density Lipoprotein Cholesterol (HDL-C) in Breast Cancer Patients of Southern Rajasthan

Despite advances in management of breast cancer, etiology is still elusive. Diet, obesity and other life style factors have been implicated in its etiology. We assessed the role of obesity and HDL-C levels in patients with rural background in etiology of breast cancer. To know the relation between obesity and incidence of breast cancer in local population. Also to know serum HDL-C level in breast cancer and its correlation with breast cancer. A nested pilot study of 50 breast cancer patients was done and matched with 50 healthy women as controls. Obesity was measured by weight, height, BMI (Body Mass Index), waist circumference (WC), Hip Circumference (HC), WC/HC ratio, and Serum High Density Lipoprotein Cholesterol (HDL-C) was measured in patients and in controls. There was no significant difference in distribution of weight (p = 0.298), height (p = 0.653), BMI (p = 0.459) and WHR (p = 0.052) among cases and controls. HDL-C level was observed to be significantly lower in cases than control group (p = 0.017).Breast cancer patients of pre menopausal age had significantly low Weight (p = 0.037) and BMI (p = 0.011) than post menopausal patients. In our study population only low HDL-C level had significant correlation with breast cancer and none of the other anthropometric measurements were associated with breast cancer. However, large population based case control and cohort studies are needed to identify low serum HDL-C as an independent predictor of increased risk of breast cancer