The multidrug resistance 1 (MDR1) gene polymorphism G-rs3789243-A is not associated with disease susceptibility in Norwegian patients with colorectal adenoma and colorectal cancer; a case control study

<p>Abstract</p> <p>Background</p> <p>Smoking, dietary factors, and alcohol consumption are known life style factors contributing to gastrointestinal carcinogenesis. Genetic variations in carcinogen handling may affect cancer risk. The multidrug resistance 1(<it>MDR1/ABCB1</it>) gene encodes the transport protein P-glycoprotein (a phase III xenobiotic transporter). P-glycoprotein is present in the intestinal mucosal lining and restricts absorption of certain carcinogens, among these polycyclic aromatic hydrocarbons. Moreover, P-glycoprotein transports various endogenous substrates such as cytokines and chemokines involved in inflammation, and may thereby affect the risk of malignity. Hence, genetic variations that modify the function of P-glycoprotein may be associated with the risk of colorectal cancer (CRC). We have previously found an association between the <it>MDR1 </it>intron 3 G-rs3789243-A polymorphism and the risk of CRC in a Danish study population. The aim of this study was to investigate if this <it>MDR1 </it>polymorphism was associated with risk of colorectal adenoma (CA) and CRC in the Norwegian population.</p> <p>Methods</p> <p>Using a case-control design, the association between the <it>MDR1 </it>intron 3 G-rs3789243-A polymorphism and the risk of colorectal carcinomas and adenomas in the Norwegian population was assessed in 167 carcinomas, 990 adenomas, and 400 controls. Genotypes were determined by allelic discrimination. Odds ratio (OR) and 95 confidence interval (95% CI) were estimated by binary logistic regression.</p> <p>Results</p> <p>No association was found between the <it>MDR1 </it>polymorphism (G-rs3789243-A) and colorectal adenomas or cancer. Carriers of the variant allele of MDR1 intron 3 had odds ratios (95% CI) of 0.97 (0.72–1.29) for developing adenomas, and 0.70 (0.41–1.21) for colorectal cancer, respectively, compared to homozygous wild type carriers.</p> <p>Conclusion</p> <p>The <it>MDR1 </it>intron 3 (G-rs3789243-A) polymorphism was not associated with a risk of colorectal adenomas or carcinomas in the present Norwegian study group. Thus, this <it>MDR1 </it>polymorphism does not seem to play an important role in colorectal carcinogenesis in this population.</p

Trends in incidence, mortality and survival in women with breast cancer from 1985 to 2012 in Granada, Spain: a population-based study

The incidence of breast cancer has increased since the 1970s. Despite favorable trends in prognosis, the role of changes in clinical practice and the introduction of screening remain controversial. We examined breast cancer trends to shed light on their determinants Overall, age-adjusted (European Standard Population) incidence rates increased from 48.0 cases × 100,000 women in 1985–1989 to 83.4 in 2008–2012, with an annual percentage change (APC) of 2.5% (95%CI, 2.1–2.9) for 1985–2012. The greatest increase was in women younger than 40 years (APC 3.5, 95%CI, 2.4–4.8). For 2000–2012 the incidence trend increased only for stage I tumors (APC 3.8, 95%CI, 1.9–5.8). Overall age-adjusted breast cancer mortality decreased (APC − 1, 95%CI, − 1.4 – − 0.5), as did mortality in the 50–69 year age group (APC − 1.3, 95%CI, − 2.2 – − 0.4). Age-standardized net survival increased from 67.5% at 5 years in 1985–1989 to 83.7% in 2010–2012. All age groups younger than 70 years showed a similar evolution. Five-year net survival rates were 96.6% for patients with tumors diagnosed in stage I, 88.2% for stage II, 62.5% for stage III and 23.3% for stage IV. Breast cancer incidence is increasing – a reflection of the evolution of risk factors and increasing diagnostic pressure. After screening was introduced, the incidence of stage I tumors increased, with no decrease in the incidence of more advanced stages. Reductions were seen for overall mortality and mortality in the 50–69 year age group, but no changes were found after screening implementation. Survival trends have evolved favorably except for the 70–84 year age group and for metastatic tumors.This study was supported by a grant from the Acción Estratégica en Salud plan for the High Resolution Project on Prognosis and Care of Cancer Patients (No. AC14/00036) awarded by the Spanish Ministry of Economy and Competitiveness and co-funded by the European Regional Development Fund (ERDF)

Alcohol intake and risk of colorectal cancer: results from the UK Dietary Cohort Consortium.

BACKGROUND: Epidemiological studies have suggested that excessive alcohol intake increases colorectal cancer (CRC) risk. However, findings regarding tumour subsites and sex differences have been inconsistent. METHODS: We investigated the prospective associations between alcohol intake on overall and site- and sex-specific CRC risk. Analyses were conducted on 579 CRC cases and 1996 matched controls nested within the UK Dietary Cohort Consortium using standardised data obtained from food diaries as a main nutritional method and repeated using data from food frequency questionnaire (FFQ). RESULTS: Compared with individuals in the lightest category of drinkers (>0-or=45 g per day. No clear associations were observed between site-specific CRC risk and alcohol intake in either sex. Analyses using FFQ showed similar results. CONCLUSION: We found no significantly increased risk of CRC up to 30 g per day of alcohol intake within the UK Dietary Cohort Consortium