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Janet E Olson

Publications and source records attributed to Janet E Olson.

16 recordsLinked to original sources
PubMed2006

A method for automatically interpreting mass spectra of 18O-labeled isotopic clusters.

16O/18O labeling is one differential proteomics technology among many that promises diagnostic and prognostic biomarkers of disease. Although the incorporation of 18O in the C-terminal carboxyl group during endoproteinase digestion in the presence of H2 18O makes the process of labeling facile, the ease and effectiveness of label incorporation have in some regards been outweighed by the difficulties in interpreting the resulting spectra. Complex isotope patterns result from the composition of unlabeled (18O(0)), singly labeled (18O(1)), and doubly labeled species (18O(2)) as well as contributions from the naturally occurring isotopes (e.g. 13C and 15N). Moreover because labeling is enzymatic, the number of 18O atoms incorporated can vary from peptide to peptide. Finally it is difficult to distinguish highly up-regulated from highly down-regulated or C-terminal peptides. We have developed an algorithm entitled regression analysis applied to mass spectrometry (RAAMS) that automatically, rapidly, and confidently interprets spectra of 18O-labeled peptides without requiring chemical composition information derived from product ion spectra. The algorithm is able to measure the effective 18O incorporation rate due to variable enzyme substrate specificity of the pseudosubstrate during the isotope exchange reaction and corrects for the 18O(0) abundance that remains in the labeled sample when using a two-step digestion/labeling procedure. We have also incorporated a method for distinguishing pure 18O(0) from pure 18O(2) peptides utilizing impure H2 18O. The algorithm operates on centroided peak lists and is therefore very fast: nine chromatograms of, on average, 1,168 spectra and containing, on average, 6,761 isotopic clusters were interpreted in, on average, 45 s per chromatogram. RAAMS is fast enough (average, 38 ms/spectrum) to allow the possibility of performing information-dependent MS/MS on a chromatographic time scale on species exceeding predetermined ratio thresholds. We describe in detail the operation of the algorithm and demonstrate its use on datasets with known and unknown ratios.

Algorithms↗
PubMed2006

A comprehensive examination of CYP19 variation and risk of breast cancer using two haplotype-tagging approaches.

BACKGROUND: Numerous studies point to a positive relationship between elevated levels of estrogens and increased risk of breast. Androgens are converted to estrogens by the aromatase enzyme, which is encoded by the CYP19 gene. We recently published resequencing data on 88 polymorphisms identified in that gene. The hypothesis tested in this study was that polymorphisms, or haplotypes, in CYP19 are related to risk of breast cancer. METHODS: Incident cases of breast cancer were identified through the Division of Medical Oncology at the Mayo Clinic in Rochester, MN. Controls were patients visiting Mayo for an annual medical examination. Controls were frequency matched to cases based on age and region of residence. Tag-polymorphisms were selected using 2 methods: (1) 12 variants using the tag-selection method of Carlson et al. (Am J Hum Genet 74:106-120, 2004); and (2) 12 variants using the haplotype method of Stram (Genet Epidemiol 27:365-374, 2004). Six SNPs were selected by both methods. Genotyping was conducted using SNPStream, TaqMan and RFLP analyses. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Analyses were conducted among all cases and controls, or stratified by estrogen receptor alpha (ER) status and/or menopausal status. RESULTS: A total of 750 cases (60% postmenopausal) and 732 controls (75% postmenopausal) were included. No association with breast cancer risk was detected for individual variants, selected tagSNPs or hap-tag SNPs despite 80% power to detect OR as low as 1.49 for minor allele frequency (MAF) of 0.10. Similarly, stratified analyses based on ER status or menopausal status failed to detect any association with breast cancer risk. CONCLUSION: These analyses suggest that variants of CYP19 are not associated with risk of breast cancer.

Alleles↗
PubMed2006

Association of family history of specific cancers with a younger age of onset of pancreatic adenocarcinoma.

BACKGROUND & AIMS: Pancreatic adenocarcinoma has been associated with several familial cancer syndromes that also predispose to other malignancies. Younger ages of onset of pancreatic cancer (PC) have been reported in families with these syndromes. METHODS: Six hundred twenty-four consecutive patients (probands) from the Mayo Clinic Pancreatic Cancer Patient Registry who completed questionnaires were analyzed for family history of cancer and cigarette smoking. The ages at diagnosis of those probands who reported a family history (first- or second-degree relative) of PC, breast, ovarian, colorectal cancer, or melanoma were compared with those probands who did not. Multivariable regression analyses were performed with age at diagnosis as the primary outcome variable. RESULTS: As expected, smokers had a younger median age of onset of PC than nonsmokers in dose-dependent fashion (P = .0003). After controlling for tobacco exposure and gender, those probands with a family history of breast (-3.23 years, P = .001), ovarian (-5.63 years, P = .005), colorectal (-3.19 years, P = .002) cancers, and melanoma (-5.75 years, P = .017) had a younger age of onset of PC than those who did not. Those with a family history of PC (-.61 years, P = .65) exhibited no difference. Probands reporting other cancers in relatives showed no difference (+.78 years, P = .49) in age of onset of PC. CONCLUSION: A family history of cancers (breast, ovarian, colorectal, melanoma) associated with specific cancer syndromes that are known to contribute also to PC risk is associated with a younger onset of PC. A family history of PC does not appear to affect age of onset of PC.

Adenocarcinoma↗
PubMed2005

Estrogen bioactivation, genetic polymorphisms, and ovarian cancer.

Recent experimental evidence has shown that catechol estrogens can be activated through metabolism to form depurinating DNA adducts and thereby initiate cancer. Limited data are available regarding this pathway in epithelial ovarian cancer. We conducted a case-control study of 503 incident epithelial ovarian cancer cases at the Mayo Clinic in Rochester, MN, and Jacksonville, FL, and a 48-county region in North Carolina. Six hundred nine cancer-free controls were frequency matched to the cases on age, race, and residence. After an interview to obtain data on risk factors, a sample of blood was collected for DNA isolation. Subjects were genotyped for seven common single nucleotide polymorphisms in four genes involved in catechol estrogen formation (CYP1A1 and CYP1B1) or conjugation (COMT and SULT1A1). Data were analyzed using logistic regression, stratified by race, and with adjustment for design factors and potential confounders. None of the individual genotypes were significantly associated with ovarian cancer risk. However, an oligogenic model that considered the joint effects of the four candidate genes provided evidence for an association between combinations of these genes and ovarian cancer status (P = 0.015). Although preliminary, this study provides some support for the hypothesis that low-penetrance susceptibility alleles may influence risk of epithelial ovarian cancer.

Adult↗
PubMed2005

Prepregnancy exposure to cigarette smoking and subsequent risk of postmenopausal breast cancer.

OBJECTIVE: To examine the association of cigarette smoking before first pregnancy with risk of postmenopausal breast cancer in a large population-based cohort. PATIENTS AND METHODS: The Iowa Women's Health Study is a prospective cohort study of 55- to 69-year-old women at baseline in 1986. In January 1986, a questionnaire was mailed to 99,826 postmenopausal women to Identify risk factors for cancer and other chronic diseases; 41,836 women responded (42.7% response rate). The primary analyses examined the associations among smoking, parity, age at first birth, and postmenopausal breast cancer. RESULTS: Of the 37,105 women in the cohort at risk, 7095 (19%) and 4186 (11%) initiated smoking before and after first pregnancy, respectively, and 2017 breast cancers were identified before December 31, 1999. Compared with parous women who never smoked, women who began smoking after their first full-term pregnancy were not at increased risk of postmenopausal breast cancer (multivariate-adjusted risk ratio, 1.03; 95% confidence interval, 0.88-1.21). However, women who began smoking before their first pregnancy had a slightly elevated risk of breast cancer (risk ratio, 1.21; 95% confidence Interval, 1.07-1.37). Results were not attenuated by adjustment for age at first pregnancy or number of live births. CONCLUSION: These data suggest that cigarette smoking is associated with a slightly greater risk of postmenopausal breast cancer for women who started smoking before their first full-term pregnancy.

Age Factors↗
PubMed2004

Bilateral oophorectomy and breast cancer risk reduction among women with a family history.

PURPOSE: We investigated whether removal of the ovaries is an appropriate risk reduction option for women at elevated risk of breast cancer based on family history of breast cancer. PATIENTS AND METHODS: This question was investigated among a group of 851 women less than age 60 who underwent bilateral oophorectomy between 1970 and 1994 for various reasons. Questionnaire information was collected from 680 (80%) and women were grouped into family risk categories. Reported occurrences of breast cancer were compared to expected rates based on the Gail model. RESULTS: The number of observed breast cancers among women in the cohort was lower than expected for all levels of familial risk, with women in the highest risk groups experiencing about half to one-fourth the number of cancers expected. The apparent protective effect of oophorectomy was stronger among women who were both premenopausal and less than age 50 at time of surgery. CONCLUSION: These data support oophorectomy as a valid breast cancer prevention option for women of all risk levels.

Adult↗
PubMed2004

Interaction of adolescent anthropometric characteristics and family history on breast cancer risk in a Historical Cohort Study of 426 families (USA).

OBJECTIVE: To determine whether the association of adolescent anthropometric characteristics with breast cancer is modified by a family history of the disease. METHODS: These interactions were evaluated in a historical cohort of 426 families of breast cancer probands diagnosed between 1944 and 1952 at the University of Minnesota. The occurrence of breast cancer and the measurement of risk factors in sisters, daughters, granddaughters, nieces and marry-ins was determined through telephone interviews and mailed questionnaires conducted from 1991-1996. Cox proportional hazards regression, accounting for age, birth cohort, adult body mass index (BMI), and clustering within families, was used to estimate relative risks (RR) and 95% confidence intervals (CIs) of breast cancer. RESULTS: Among 4632 women from 426 families available for analysis, there were 175 breast cancers. There was a strong interaction between degree of relationship to proband and relative weight at age 12 on breast cancer risk ( p < 0.001). Among sisters and daughters of the probands, risk of breast cancer was slightly increased in those with below average weight at age 12 (RR = 1.55; 95% CI = 0.66-3.64), and strongly increased in those with above average weight (RR = 4.25; 95% CI = 1.71-10.5), compared to those with average weight. In contrast, among marry-ins, there was a weak positive association for those with below average weight at age 12 (RR = 1.61; 95% CI = 0.91-2.83), while there was an inverse association for above average weight (RR = 0.75; 95% CI = 0.26-2.16), compared to those with average weight. There were no significant interactions between degree of relationship to proband and height ( p = 0.55), weight at age 18 ( p = 0.22) and BMI at age 18 ( p = 0.63) on breast cancer risk. CONCLUSIONS: Family history appears to modify the effect of obesity in early adolescence on subsequent breast cancer risk, and may identify differing etiologic pathways.

Adolescent↗
PubMed2004

Does folate intake decrease risk of postmenopausal breast cancer among women with a family history?

BACKGROUND: Several recent studies suggest that adequate dietary folate may attenuate the risk of breast cancer associated with intake of alcohol. We examined whether the putative benefit extends to women with a family history (FH) of breast cancer using a cohort of 33,552 postmenopausal women aged 55-69 years in 1986. METHOD: Folate and alcohol intake was estimated from a food frequency questionnaire completed at baseline. Folate was categorized as upper 50th, 31st-50th, 11th-30th, and <10th percentiles. Alcohol use was initially classified into three levels; never drinkers, less than the median and greater than the median. Subsequent models collapsed levels of intake to any versus none. Occurrence of breast cancer was determined through linkage to the Iowa SEER registry. Multivariate-adjusted relative risks (RR) and 95% confidence intervals (CI) were estimated through Cox proportional hazards regression, stratified on FH using non-drinkers with high folate and no FH as the referent group. RESULTS: Through 14 years, 1823 incident cases were identified, 308 among FH+ women. Among FH- women, low folate was not a risk factor among non-drinkers (RR = 0.96, CI = 0.73-1.26), but was among drinkers (RR = 1.40, CI = 1.05-1.86). Drinkers with high folate were not at elevated risk (RR = 1.03, CI = 0.89-1.19). Among FH+ women, low folate was a risk factor among drinkers (RR = 2.21, CI = 1.43-3.41) and non-drinkers (RR = 2.39, CI = 1.36-4.20). Further, drinkers with high folate remained at increased risk (RR = 1.67, CI= 1.30-2.14). However, FH+ women with high folate who did not drink alcohol had no elevated risk. CONCLUSION: These results suggest that folate may attenuate the risks of postmenopausal breast cancer associated with family history, but only if alcohol use is avoided or minimized.

Aged↗
PubMed2002

The continuing increase in the incidence of primary central nervous system non-Hodgkin lymphoma: a surveillance, epidemiology, and end results analysis.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an extranodal form of non-Hodgkin lymphoma arising in the craniospinal axis. The incidence of PCNSL appears to be increasing. METHODS: PCNSL incidence data from 1973-1997 were obtained from the nine Surveillance, Epidemiology and End Results (SEER) registries. To limit the influence of the human immunodeficiency virus on incidence rates, data of never-married males and females and persons of unknown marital status were excluded. As a surrogate for new technology, SEER data were reviewed by dates of diagnosis (surrogate for imaging) and compared with glioma incidence (surrogate for stereotactic neurosurgery and improved diagnostic neuropathology). Age-adjusted incidence rates were estimated and compared for the period prior to computed tomography (CT) (1973-1984) and the magnetic resonance imaging (MRI) period (1985-1997). The estimated annual percent change was calculated based on linear regression analyses using SEER*STAT. RESULTS: The incidence of PCNSL appears to be increasing in all SEER registries examined. All age groups demonstrated an increase over time. This increase was observed both in the CT era as well as in the MRI era. PCNSL age-adjusted incidence (0.15 to 0.48, a 3-fold increase) outpaced that of systemic lymphoma (14.1 to 18.5, a 33% increase) for the same registries over the same time periods. The rate of increase has begun to slow since 1985; the estimated annual percent change for PCNSL was three-fold higher during the period 1973-1985 compared with 1986-1997. CONCLUSION: The incidence rate of PCNSL continues to rise. The increase is evident in all age groups and in both genders. Data from the current study suggest that improved diagnostic tools, such as CT or MRI, cannot explain this increase.

Adult↗
PubMed2002

Postmenopausal cancer risk after self-reported endometriosis diagnosis in the Iowa Women's Health Study.

BACKGROUND: Endometriosis, the presence of endometrial tissue outside the uterus, has an estimated prevalence between 4% and 10%. A recent study reported that women with a hospital discharge diagnosis of endometriosis were at increased risk of cancer at any site, breast cancer, ovarian cancer, and hematopoietic malignancies, especially non-Hodgkin lymphoma (NHL). METHODS: The authors examined whether self-reported diagnosis of endometriosis was associated with increased risk of various cancers in the Iowa Women's Health Study. Incident cancer cases were identified from 1986 through 1998. Cox proportional hazards regression models were used to calculate relative risks and 95% confidence intervals for the particular cancers of interest. RESULTS: Of 37,434 participants in this analysis, 3.8% reported a history of endometriosis at baseline in 1986. After 13 years of follow-up, 1795 breast, 188 ovarian, and 243 NHL cases were detected in the cohort. Endometriosis was not associated with risk of all cancers combined (age-adjusted relative risk [RR], 0.9; 95% confidence interval [CI], 0.7-1.2), breast carcinoma (RR, 1.0; 95% CI, 0.8-1.3), or ovarian carcinoma (RR, 0.8; 95% CI, 0.2-2.4). However, endometriosis was significantly associated with risk of NHL (age-adjusted RR, 1.8; 95% CI, 1.0-3.0), especially diffuse NHL (RR, 3.2; 95% CI, 1.8-5.6). Multivariate adjustment had minimal effect on the point estimates of risk (NHL RR, 1.7; 95% CI, 0.97-2.7; diffuse NHL RR, 3.3; 95% CI, 1.9-5.9). Endometriosis was not associated with elevated risk of lung, urinary tract, endometrial, melanoma, or colorectal carcinomas (RRs, 1.2, 0.8, 1.2, 0.7, and 0.7, respectively). CONCLUSIONS: These results corroborate a previously reported association between endometriosis and increased risk of NHL but not cancer at other sites.

Aged↗
PubMed2002

Interaction of waist/hip ratio and family history on the risk of hormone receptor-defined breast cancer in a prospective study of postmenopausal women.

The authors previously reported an interaction of waist/hip ratio and family history on the risk of breast cancer in the Iowa Women's Health Study. Here they reexamine this association based on 9 additional years of follow-up, stratifying on tumor receptors for estrogen and progesterone. Data on risk factors and family history of breast cancer were ascertained in 1986. The occurrences of breast cancer and estrogen receptor/progesterone receptor were determined through the Iowa Surveillance, Epidemiology, and End Results' registry. Rate ratios were elevated with increasing weight and body mass index and decreasing body mass index at age 18 years, but they did not vary by family history. There was no association with height, waist circumference, or waist/hip ratio. A linear trend of increasing risk with increasing waist/hip ratio was observed among family history-positive women (p = 0.06) but not among family history-negative women (p = 0.87). This apparent interaction (p = 0.09) was examined by estrogen receptor or progesterone receptor status. When stratified on family history and estrogen receptor, no clear patterns were evident. In contrast, family history-positive women in the upper quintile of the waist/hip ratio were at 2.2-fold greater risk of progesterone receptor-negative tumors compared with those in the lowest quintile (95% confidence interval: 0.9, 5.8). Thus, the previously reported interaction between family history and waist/hip ratio is still (weakly) evident and appears to reflect risk for progesterone receptor-negative tumors.

Abdomen↗
PubMed2002

A prospective, blinded assessment of the impact of preoperative staging on the management of rectal cancer.

BACKGROUND & AIMS: The influence of preoperative staging of rectal carcinoma on therapeutic decisions is uncertain. The use of fine-needle aspiration (FNA) of perirectal nodes in this setting has not been evaluated. The aim of this prospective, blinded study of patients with rectal cancer was to assess the impact of preoperative staging on treatment decisions and compare the tumor (T), nodal (N) staging performance characteristics of pelvic computed tomography (CT), rectal endoscopic ultrasonography (EUS), and EUS FNA. METHODS: Eighty consecutive patients with newly diagnosed rectal cancer were prospectively evaluated. Therapy decisions were recorded after sequential disclosure of staging information to the patient's surgeon. RESULTS: In 31% of patients (95% confidence interval, 21%-42%), EUS staging information changed the surgeon's original treatment plan based on CT alone. The further addition of FNA changed therapy in one patient. T staging accuracy was 71% (CT) and 91% (EUS) (P = 0.02); N staging accuracy was 76% (CT), 82% (EUS), and 76% (EUS FNA) (P = NS). CONCLUSIONS: Preoperative staging with EUS results in more frequent use of preoperative neoadjuvant therapy than if staging was performed with CT alone. The addition of FNA only changed the management of one patient, whereas FNA did not significantly improve N staging accuracy over EUS alone. FNA seems to offer the most potential for impacting management in those patients with early T stage disease, and its use should be confined to this subgroup of patients. EUS is more accurate than CT for determining T stage of rectal carcinoma.

Aged↗
PubMed2002

High-folate diets and breast cancer survival in a prospective cohort study.

Recent evidence suggests that adequate dietary folate may attenuate the risk of breast cancer associated with intake of alcohol. However, patients with breast cancer have been commonly treated with antifolate chemotherapies. The present analysis was performed to test the hypothesis that high folate intake may diminish the effectiveness of chemotherapy and, therefore, adversely influence survival. Women at risk of postmenopausal breast cancer (n = 37,105) participated in the Iowa Women's Health Study. Total folate intake (diet + supplements) was estimated from a food frequency questionnaire administered at baseline in 1986 and categorized into tertiles. From all incident breast cancer cases ascertained in the cohort, we selected those with a diagnosis between 1986 and 1994, chemotherapy as first course of treatment, and adequate diet assessment. Mortality was determined through the State Health Registry of Iowa and the National Death Index. Cox regression was used to estimate survival while adjusting for important covariates. Through 14 yr of follow-up, 80 deaths occurred among the 177 breast cancer cases treated with chemotherapy. Among these patients, high folate intake was not associated with worse survival. After adjustment for age, extent of disease, total calories, alcohol, and estrogen receptor status, women with total folate intake in the highest tertile had a mortality risk ratio of 0.88 (95% confidence interval = 0.44-1.76) compared with cases in the lowest tertile of folate. These findings, although preliminary, afford some reassurance that folate supplementation is unlikely to have a significant adverse effect on survival after chemotherapy for breast cancer.

Aged↗
PubMed2002

Interaction of dietary folate intake, alcohol, and risk of hormone receptor-defined breast cancer in a prospective study of postmenopausal women.

Alcohol intake is an established risk factor for breast cancer, but the underlying mechanism remains unknown. Four recent studies have described interactions of alcohol and low folate intake. We examined this interaction on the risk of postmenopausal breast cancer stratified by tumor receptor status for estrogen (ER) and progesterone (PR). The Iowa Women's Health Study is a prospective cohort study of 34,393 at-risk women. Alcohol use and folate intake from diet and supplements were estimated at baseline in 1986 through a semiquantitative food frequency questionnaire. Through 1999, 1,875 cases of breast cancer were identified through linkage to the Iowa Surveillance, Epidemiology, and End Results registry. Compared with nondrinkers with folate intakes above the 50(th) percentile, women with low folate and high alcohol were at 1.43-fold greater risk (1.02-2.02). When stratified by tumor receptor status for ER or PR, the risks for low folate/high alcohol were 2.1 (1.18-3.85), 1.0 (0.76-1.42), 1.2 (0.88-1.70), and 1.2 (0.69-2.02) for ER-, ER+, PR+, and PR- tumors, respectively. Because the results were limited primarily to ER- tumors, one plausible interpretation of these data is that alcohol influences breast cancer through its metabolite, acetaldehyde, rather than through effects on ER levels and receptor-mediated pathways.

Acetaldehyde↗
PubMedDate not supplied

Recreational physical activity and risk of postmenopausal breast cancer based on hormone receptor status.

BACKGROUND: Physical activity is a potentially modifiable breast cancer risk factor. There is considerable recent evidence to suggest that risk factors for breast cancer differ based on its subtype, particularly estrogen receptor (ER)/progesterone receptor (PR) status, but this has been less well studied for physical activity. The objective of this study was to examine the association of physical activity with breast cancer incidence based on ER/PR status of the tumor. METHODS: The Iowa Women's Health Study is a prospective cohort study of 41 836 postmenopausal women. Recreational physical activity was self-reported on the baseline questionnaire, and 3 levels (high, medium, and low) were defined. Breast cancer incidence and ER/PR status, through 18 years of follow-up, were ascertained by linkage with the Iowa Surveillance, Epidemiology, and End Results Cancer Registry. Cox proportional hazards models were used to estimate multivariate relative risks (RRs) and 95% confidence intervals (CIs) of breast cancer, adjusting for other breast cancer risk factors. RESULTS: During 554 819 person-years of follow-up, 2548 incident cases of breast cancer were observed. Compared with low physical activity, high physical activity levels were inversely associated with risk of breast cancer (RR, 0.86; 95% CI, 0.78-0.96), and there were inverse associations for ER-positive (ER+)/PR-positive (RR, 0.87; 95% CI, 0.75-1.00), ER+/PR-negative (PR-) (RR, 0.67; 95% CI, 0.47-0.96), and ER-negative/PR- (RR, 0.80; 95% CI, 0.56-1.14) tumors. Further adjustment for body mass index attenuated the overall association with breast cancer (RR, 0.91; 95% CI, 0.82-1.01) and for ER+/PR-positive tumors (RR, 0.94; 95% CI, 0.81-1.08), while there was no change for ER+/PR- tumors (RR, 0.66; 95% CI, 0.46-0.94). CONCLUSIONS: Higher recreational physical activity might reduce the risk of postmenopausal breast cancer overall. Risk reduction varies by ER/PR status of the tumor, being most marked for ER+/PR- tumors, which, in general, have been associated with a clinically more aggressive tumor phenotype. If confirmed in additional studies, these results would suggest that additional mechanisms, besides an effect on body mass, may account for observed protective effects of physical activity in reducing breast cancer.

Aged↗