Janet E. Olson

Diet and risk of colon cancer in a large prospective study of older women: An analysis stratified on family history (Iowa, United States)

Objective: The purpose was to investigate whether dietary associations with risk of colon cancer in women differ by family history of the disease.Methods: Data were analyzed from a prospective cohort study of 35,216 Iowa (United States) women aged 55 to 69 years at baseline. Through 31 December 1995, 241 colon cancers were identified through record linkage with the State Health Registry. The cohort was stratified on family history of colon cancer in first-degree relatives; nutrient intakes were divided into tertiles.Results: Analyses using Cox regression revealed that the association of most dietary components with colon cancer incidence were similar for individuals with and without a family history. However, total calcium intake was associated inversely with colon cancer among women with a negative family history (relative risk [RR]=0.50 for upper cf lower tertile, P < 0.001), but was unrelated to incidence for women with a positive family history (RR=1.1 for upper cf lower tertile, P=0.69). Similarly, total vitamin E intake was associated with lower risk among women with a negative family history (RR=0.67 for upper cf lower tertile, P=0.04), but not among women with a positive family history (RR=0.87 for upper cf lower tertile, P=0.67). High intakes of fiber, fruits, and vegetables were each weakly inversely associated with risk among family-history negative women, but not among family-history positive women.Conclusions: These data, if corroborated, suggest that dietary factors typically associated with lower risk may be less effective risk-reduction interventions against colon cancer for individuals with a family history of colon cancer.

Association Between a Germline OCA2 Polymorphism at Chromosome 15q13.1 and Estrogen Receptor–Negative Breast Cancer Survival

BACKGROUNDnTraditional prognostic factors for survival and treatment response of patients with breast cancer do not fully account for observed survival variation. We used available genotype data from a previously conducted two-stage, breast cancer susceptibility genome-wide association study (ie, Studies of Epidemiology and Risk factors in Cancer Heredity [SEARCH]) to investigate associations between variation in germline DNA and overall survival.nnnMETHODSnWe evaluated possible associations between overall survival after a breast cancer diagnosis and 10 621 germline single-nucleotide polymorphisms (SNPs) from up to 3761 patients with invasive breast cancer (including 647 deaths and 26 978 person-years at risk) that were genotyped previously in the SEARCH study with high-density oligonucleotide microarrays (ie, hypothesis-generating set). Associations with all-cause mortality were assessed for each SNP by use of Cox regression analysis, generating a per rare allele hazard ratio (HR). To validate putative associations, we used patient genotype information that had been obtained with 5 nuclease assay or mass spectrometry and overall survival information for up to 14 096 patients with invasive breast cancer (including 2303 deaths and 70 019 person-years at risk) from 15 international case-control studies (ie, validation set). Fixed-effects meta-analysis was used to generate an overall effect estimate in the validation dataset and in combined SEARCH and validation datasets. All statistical tests were two-sided.nnnRESULTSnIn the hypothesis-generating dataset, SNP rs4778137 (C>G) of the OCA2 gene at 15q13.1 was statistically significantly associated with overall survival among patients with estrogen receptor-negative tumors, with the rare G allele being associated with increased overall survival (HR of death per rare allele carried = 0.56, 95% confidence interval [CI] = 0.41 to 0.75, P = 9.2 x 10(-5)). This association was also observed in the validation dataset (HR of death per rare allele carried = 0.88, 95% CI = 0.78 to 0.99, P = .03) and in the combined dataset (HR of death per rare allele carried = 0.82, 95% CI = 0.73 to 0.92, P = 5 x 10(-4)).nnnCONCLUSIONnThe rare G allele of the OCA2 polymorphism, rs4778137, may be associated with improved overall survival among patients with estrogen receptor-negative breast cancer.

Family histories of diabetes mellitus and breast cancer and incidence of postmenopausal breast cancer.

Diabetes-associated endocrine factors may influence the growth of some breast tumors. Therefore, one might expect an association of family history of diabetes mellitus with breast cancer incidence. We analyzed data from a cohort study of 41,837 women ages 55-69 years. During 10 years of follow-up, we identified 1,013 incident cases of breast cancer. There was no consistent association between family history of diabetes mellitus and family history of breast cancer, except among sisters. Women with a family history of diabetes had a higher prevalence of breast cancer risk factors, but family history of diabetes was not associated with risk of postmenopausal breast cancer, regardless of family history of breast cancer status.

Caudal vena cava obstruction caused by redundant pacemaker lead in a dog.

Inferior vena cava obstruction, a rare but serious complication of transvenous pacemaker lead placement in humans, has not been reported in dogs. We describe this complication in a dog that developed ascites 8 months after pacemaker implantation. Radiography disclosed a loop of redundant lead within the caudal vena cava (CVC), and angiography demonstrated obstruction to blood flow. Withdrawal of the loop from the CVC did not restore blood flow. Persistent obstruction was suspected secondary to fibrosis resulting from vascular damage caused by the loop of lead. Angioplasty of the CVC obstruction restored blood flow and resolved the dogs clinical signs.

RAD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.

Palliative balloon angioplasty in a cat with right pulmonary arterial branch stenoses and concurrent absence of the left pulmonary artery.

Unilateral absence of the left or right pulmonary artery with concurrent contralateral pulmonary arterial branch stenoses is an exceptionally rare disorder. We describe this anomaly in a cat with severe exercise intolerance and respiratory distress. Transthoracic echocardiography and angiography demonstrated the absence of the left pulmonary artery with concurrent right pulmonary branch stenosis. Palliative balloon angioplasty of the right pulmonary artery substantially reduced right ventricular systolic pressure load and alleviated the patients clinical signs.

Patent ductus arteriosus occlusion in small dogs utilizing a low profile Amplatz® canine duct occluder prototype.

OBJECTIVESnTo develop procedural methodology and assess the safety, utility and effectiveness of a low profile Amplatz(®) canine duct occluder (ACDO) prototype in dogs deemed too small to undergo ductal occlusion with the commercially-available ACDO device.nnnANIMALSnTwenty-one dogs with left-to-right shunting patent ductus arteriosus (PDA). Dogs were ≥1.5xa0kg but considered too small to accommodate a 6xa0Fr catheter or 4xa0Fr sheath within the femoral artery.nnnMETHODSnProspective canine study using a low profile ACDO prototype delivered through a 4xa0Fr catheter via a femoral arterial approach. Procedural methods, fluoroscopy time, perioperative complications, and residual ductal flow were evaluated, and angiographic ductal morphology and dimensions were tabulated.nnnRESULTSnAll 21 dogs underwent successful ductal occlusion using the prototype device, 4xa0Fr catheter, and right femoral artery approach. No perioperative complications or device embolization occurred. The median minimal ductal diameter was 1.9xa0mm (range, 0.4-3.4), and the median device size deployed was 4xa0mm (range, 3-6). Complete ductal occlusion was noted in 17 dogs (81%) on post-deployment angiography. Twenty dogs (95%) had no residual flow on echocardiography performed the following day. In the 17 dogs (81%) that returned for a long-term (≥3months) follow-up evaluation, all had complete ductal occlusion based on echocardiography.nnnCONCLUSIONSnThe low profile ACDO prototype is a safe and effective method of PDA occlusion in the small dog. The deployment procedure appears of similar technical difficulty to the commercially available ACDO.