Citations

Abstract Background: Folate-associated one-carbon metabolism (FOCM) may play an important role in colorectal carcinogenesis. Variation in FOCM genes may explain some of the underlying risk of colorectal cancer. Methods: This study utilized data from 1,805 population-based colorectal cancer cases and 2,878 matched sibling controls from the Colon Cancer Family Registry. We used a comprehensive haplotype tagging single nucleotide polymorphism (tagSNP) approach to select 395 tagSNPs in 15 genes involved in folate and vitamin B12 metabolism. Genotyping was done using the Illumina GoldenGate or Sequenom platforms. Risk factor and dietary data were collected using self-completed questionnaires. Microsatellite instability (MSI) status was determined using standard techniques, and tumor subsite was obtained from pathology reports. The association between SNPs and colorectal cancer was assessed using conditional logistic regression with sibships as the matching factor and assuming a log additive or codominant model. Results: In the log additive model, two linked (r2 = 0.99) tagSNPs in the DHFR gene (rs1677693 and rs1643659) were associated with a significant decrease in colorectal cancer risk after correction for multiple testing (odds ratio, 0.87; 95% confidence interval, 0.71-0.94; P = 0.029; and odds ratio, 0.87; 95% confidence interval, 0.71-0.95; P = 0.034 for rs1677693 and rs1643659, respectively). These two linked (r2 = 0.99) tagSNPs and one tagSNP in the MTR gene (rs4659744) were significantly associated with reduced colorectal cancer risk only among individuals not using multivitamin supplements. Conclusions: Overall, we found only moderate evidence that genetic variation in 15 folate pathway genes may affect colorectal cancer risk except in non–multivitamin users. Impact: This study suggests that multivitamin supplement use may modify the association between folate pathway genes and colorectal cancer risk in a post-folic-acid-supplemented population. Cancer Epidemiol Biomarkers Prev; 19(7); 1812–21. ©2010 AACR.

This study was performed to review the safety and outcome of total shoulder replacements in patients who are ≥ 80 years of age. A total of 50 total shoulder replacements in 44 patients at a mean age of 82 years (80 to 89) were studied. Their health and shoulder status, the operation and post-operative course were analysed, including pain, movement, patient satisfaction, medical and surgical complications, radiographs, the need for revision surgery, and implant and patient survival. A total of 27 patients had an ASA classification of III or IV and medical abnormalities were common. Of the 13 shoulders with bony deficiency of the glenoid, nine required grafting. The duration of hospital stay was prolonged and blood transfusions were common. There were no peri-operative deaths. The mean follow-up was for 5.5 years (2 to 12). Pain was significantly reduced (p < 0.001) and movement improved in active elevation and both external and internal rotation (p < 0.001). Using the Neer scale for assessing outcome, 40 (80%) shoulders had an excellent or satisfactory result. There were medical or surgical complications in 17 cases. Four shoulders developed radiological evidence of loosened glenoid components, and three of these had a poor outcome. Three other shoulders required revision, two for instability. By the time of this review 39 of the patients had died from unrelated causes at a mean of 7.5 years (0.8 to 16.4) after surgery. Total shoulder replacement is a relatively effective treatment in this elderly group of patients. However, there is a requirement for more intense patient care in the peri-operative period, and non-fatal medical or surgical complications are common. Most of these elderly patients will have a comfortable functional shoulder for the rest of their lives.