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Background:The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk.Methods:We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. Anti-Mullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (ORlog2). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics.Results:Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (ORlog2: 1.07 (0.99-1.17)), or with any of the examined subgroups.Conclusions:Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to examine the associations between aromatase inhibitors (AIs) and side effects less frequently reported in the literature, including difficulty concentrating, forgetfulness, hair loss, and numbness in the extremities.Methods: Data were analyzed from a cohort of 146 breast cancer patients initiating AI therapy and followed for 1 year and a cohort of 144 postmenopausal women without a history of cancer followed for 6 months. At baseline (prior to AI therapy for breast cancer patients), and at 3 months, 6 months, and 1 year (for breast cancer patients only), a comprehensive questionnaire was administered that ascertained data on symptoms. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression for new onset of symptoms among the breast cancer patients compared to the women without a history of cancer.Results: Among the breast cancer patients, 34.2% were treated with chemotherapy prior to AI treatment. Over the first 6 months of AI treatment, breast cancer patients had significantly higher odds of reporting new onset of forgetfulness (OR 4.00; 95% CI 1.67, 9.59), difficulty concentrating (OR 2.73; 95% CI 1.29; 5.78), hair loss (OR 4.12; 95% CI 1.86, 9.17), and numbness/tingling in the extremities (OR 2.47; 95% CI 1.09, 5.62) compared to women without a history of cancer. Similar increases in odds were observed for the subgroup of women not treated with chemotherapy versus the comparison group.Conclusions: AI-related symptoms should be monitored and addressed so that adherence to therapy is maintained. [ABSTRACT FROM AUTHOR]

Purpose: Biologic evidence suggests that the Insulin-like growth factor (IGF)-family may be involved in the etiology of epithelial invasive ovarian cancer (EOC). However, prospective studies investigating the role of IGF-I in ovarian carcinogenesis have yielded conflicting results.Methods: We pooled and harmonized data from 6 case-control studies nested within the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis IGF-I concentrations and subsequent risk of EOC. We evaluated IGF-I concentrations and risk of EOC overall and by tumor subtype (defined by histology, grade, stage) in 1,270 cases and 2,907 matched controls. Multivariable conditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI).Results: Doubling of IGF-I concentration was associated with significantly lower risk of overall EOC [ORlog2 = 0.82; CI 0.72-0.93]. We observed no heterogeneity by tumor characteristics (e.g., histology, p het = 0.62), menopausal status at blood collection (p het = 0.79), or age at diagnosis (p het = 0.60).Conclusions: These results suggest that IGF-I concentrations are inversely associated with EOC risk, independent of histological phenotype. Future prospective research should consider potential mechanisms for this association, including, considering other members of the IGF-family to better characterize the role of IGF-signaling in the etiology of EOC. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome components have been associated with colorectal cancer in several studies; however, evidence for colorectal adenomas is limited. Thus, we evaluated the association between markers of the metabolic syndrome with colorectal adenoma development in a nested case-control study.Methods: Colorectal adenoma cases (n = 132) and matched controls, who had a negative sigmoidoscopy or a colonoscopy (n = 260), were identified between baseline in 1989 and 2000 among participants in the CLUE II cohort of Washington County, Maryland. Concentrations of C-peptide, insulin-like growth factor binding protein-1, glycosylated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured in baseline blood specimens. Body mass index was calculated using baseline height and weight. Use of medications to treat diabetes mellitus was self-reported at baseline. Blood pressure was measured at baseline. Distributional cutpoints of the latter markers were used to define the metabolic syndrome components (hyperinsulinemia, hyperglycemia, obesity, dyslipidemia, and hypertension) present at baseline.Results: No statistically significant associations with adenomas were observed for the markers of the metabolic syndrome, with the exception of a strong positive association for use of diabetes medications (OR, 8.00; 95% CI, 1.70-37.67), albeit based on small numbers.Conclusion: Our findings do not support that components of the metabolic syndrome influence risk of colorectal adenomas, except possibly for severe diabetes mellitus warranting medical treatment. [ABSTRACT FROM AUTHOR]

Statin drugs appear to protect against advanced and possibly high-grade prostate cancer, perhaps through cholesterol-lowering. Thus, we evaluated the association between plasma cholesterol and prostate cancer. We conducted a prospective study in the CLUE II cohort of Washington County, MD. Included were 6,816 male county residents aged 35+ years old who did not have a cancer diagnosis at baseline in 1989. Plasma cholesterol, measured enzymatically at baseline, was categorized by clinical cutpoints. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for total (n = 438) and high-grade (Gleason sum > or =7, n = 137) prostate cancer. Compared to men with high cholesterol (> or =240 mg/dl), men with desirable (<200 mg/dl) or borderline (200 to <240 mg/dl) levels were less likely to develop high-grade prostate cancer, particularly when restricting to organ-confined cases (HR: 0.68, 95% CI 0.40-1.18; P trend = 0.12) and among men with higher BMI (HR: 0.36, 95% CI 0.16-0.79; P trend = 0.02). Results were unchanged after excluding cholesterol-lowering drug users. Cholesterol was not associated with total prostate cancer. Our study supports two prior ones suggesting that cholesterol influences risk of high-grade prostate cancer, and indirectly supports the hypothesis that cholesterol-lowering is a mechanism by which statins are protective. [ABSTRACT FROM AUTHOR]

Objective and Methods: The association of 17 candidate single nucleotide polymorphisms (SNPs) in IL10 and other immune response genes (CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and genes related to obesity (PPARG, TCF7L2, ADIPOQ, LEP) with colorectal cancer was investigated. Haplotype tagging SNPs were chosen for IL10, CRP, and TLR4. Incident colorectal cancer cases (n = 208) and matched controls (n = 381) were identified between baseline in 1989 and 2003 among participants in the CLUE II cohort. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression.Results: Compared with the AA genotype at the candidate IL10-1082 locus (rs1800896), carrying one (OR, 0.79; 95% CI, 0.53-1.18) or two (OR, 0.58; 95% CI, 0.35-0.95) G alleles, a known higher producer of the anti-inflammatory cytokine IL-10, was associated with lower risk of colorectal cancer (p trend = 0.03). Statistically significant associations with colorectal cancer were observed for three tagSNPs in IL10 (rs1800890, rs3024496, rs3024498) and one common haplotype, but these associations were due to high linkage disequilibrium with IL10-1082. Two CRP haplotypes (global p = 0.04) and TLR4 tagSNPs (rs7873784, rs11536891), but not TLR4 haplotypes, were associated with colorectal cancer.Conclusions: Our study suggests that polymorphisms in IL10, and also possibly in CRP and other genes related to immune response or obesity may be associated with colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: The association between prediagnostic interleukin-6 (IL-6) concentrations and risk of colorectal cancer was evaluated in a nested case-control study and a meta-analysis of prospective studies.Methods: Colorectal cancer cases (n = 173) and matched controls (n = 345) were identified between 1989 and 2000 among participants in the CLUE II cohort of Washington Country, Maryland. Matched odds ratios and the corresponding 95 % confidence intervals (CIs) were estimated using conditional logistic regression models.Results: Participants in the highest third of plasma IL-6 concentration had a 2.48 times higher risk of colon cancer compared to participants in the bottom third (95 % CI 1.26-4.87; p-trend 0.02) after multivariate adjustment. This association did not differ according to the stage of disease, age, sex, or other potential modifying variables and remained statistically significant after adjustment for C-reactive protein concentrations. No statistically significant association was observed for rectal cancer risk. The meta-analysis of six prospective studies yielded an increased but borderline statistically significant risk of colon cancer per 1 U increase in naturally logarithm-transformed IL-6 (summary RR 1.22; 95 % CI 1.00-1.49; I (2) 46 %). An inverse association was noted for rectal cancer (RR 0.69; 95 % CI 0.54-0.88; I (2) 0 %), but there was evidence for small-study effects (p 0.02).Conclusion: Our findings provide support for a modest positive association between IL-6 concentrations and colon cancer risk. More work is needed to determine whether IL-6 is a valid marker of colorectal inflammation and whether such inflammation contributes to colon and rectal cancer risk. [ABSTRACT FROM AUTHOR]

Purpose: Although cancer is often thought of as a teachable moment, many cancer survivors do not adhere to behavioral recommendations that might improve their health. This study explored health care providers' perspectives on the importance and feasibility of addressing behavior change, specifically healthy diet, with cancer survivors.Methods: In-depth interviews were conducted with 33 health care providers who care for posttreatment survivors of breast cancer, prostate cancer, and non-Hodgkin's lymphoma. Interviews were analyzed thematically.Results: Health care providers emphasized the strength of evidence linking diet/obesity to recurrence in their assessment of the importance of promoting dietary change among their survivor patients. Cancer specialists (e.g., oncologists, surgeons) generally brought up dietary change with patients if they considered the evidence to be strong. In contrast, primary care providers viewed health promotion as important for all patients and reported treating cancer survivor patients the same as others when it came to making dietary recommendations. There was a lack of consensus among providers on the best timing to bring up behavior change. Providers described specific subgroups of patients who they saw as more motivated to make behavior changes and patient barriers to making dietary changes.Conclusions: Health care providers can play an important role in promoting healthy diet among cancer survivors. As the evidence base around diet and cancer recurrence/prognosis grows, it is important that this information is communicated to providers. Strategies such as incorporating behavior change messages into survivor care plans may help standardize recommendations to survivors. [ABSTRACT FROM AUTHOR]

Objective: This study aims to examine the associations between musculoskeletal pain and health-related quality of life (HR-QOL) among breast cancer patients on aromatase inhibitors (AIs) and women without a history of breast cancer. Methods: A cross-sectional study was conducted among 68 breast cancer patients on AIs for an average of 3.5 years and 137 postmenopausal women without a history of cancer. Musculoskeletal pain was assessed using a 10-cm visual analog scale; HR-QOL was examined using the Medical Outcomes Study Short Form (SF-36) health survey. Linear regression was used to estimate the associations between pain and HR-QOL in both groups. Results: Approximately 64 % of the breast cancer patients and women in the comparison group reported musculoskeletal pain. Among women with breast cancer, those with pain had significantly lower HR-QOL scores in the physical (52.2 vs. 42.6; p < 0.001) and mental (52.7 vs. 45.5; p = 0.01) component summary scores compared with those without pain. In the comparison group, pain was associated with significantly lower scores in the physical (55.4 vs. 46.0; p < 0.001), but not the mental, component summary score (52.1 vs. 52.4; p = 0.82). The significant associations between pain and HR-QOL persisted after confounder adjustment in both groups. Among women with similar severity of pain, breast cancer patients reported significantly lower HR-QOL in the mental summary component compared with the women in the comparison group. Conclusions: Among breast cancer patients, musculoskeletal pain adversely affects both mental and physical components of HR-QOL. Preventing or treating AI-associated musculoskeletal pain may improve overall HR-QOL among breast cancer patients treated with AIs. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to examine differences in physical functioning limitations among African-American and white breast cancer survivors. Methods: Data were analyzed from 115 African-American and 712 white breast cancer survivors who responded to a hospital registry-based survey. Physical functioning limitations were assessed using a series of eight questions in which individuals were asked about their ability to perform a physical task such as walking a quarter of a mile. A four-category summary score, representing overall severity of limitation, was created using participant responses to the eight questions. Ordinal logistic regression was used to estimate the odds ratio (OR) and 95 % confidence interval (CI) for the association between race and physical functioning limitation adjusted for potential confounders. Results: In the unadjusted model, the African-American breast cancer survivors were more than twice as likely to have a greater degree of physical functioning limitation compared to their white counterparts (OR 2.31; 95 % CI 1.59, 3.38). After adjustment for covariates, including body mass index (BMI), the race OR was attenuated and no longer statistically significant (OR 1.44; 95 % CI 0.92, 2.27). Conclusions: Findings from this study showed that African-American breast cancer survivors were more likely to have worse physical functioning limitations than their white counterparts; however, much of this disparity was due to racial differences in other variables such as BMI. Future research should focus on effective interventions targeting modifiable risk factors of physical functioning limitations among breast cancer survivors with the goal of improving quality of life. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the associations between aromatase inhibitor therapy and hair loss or hair thinning among female breast cancer survivors. Data were analyzed from 851 female breast cancer survivors who responded to a hospital registry-based survey. Data on hair loss, hair thinning, demographic characteristics, and health habits were based on self-report; data on aromatase inhibitor therapy were collected on the survey and verified using medical record review. Logistic regression was used to estimate the odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations between aromatase inhibitor therapy and the hair outcome variables adjusted for potential confounders, including age and chemotherapy treatment. The results showed that 22.4 % of the breast cancer survivors reported hair loss and 31.8 % reported hair thinning. In the confounder-adjusted analyses, breast cancer survivors who were within 2 years of starting aromatase inhibitor treatment at the time of survey completion were approximately two and a half times more likely to report reporting hair loss (OR 2.55; 95 % CI 1.19–5.45) or hair thinning (OR 2.33; 95 % CI 1.10–4.93) within the past 4 weeks compared to those who were never treated with an aromatase inhibitor. Current aromatase inhibitor use for two or more years at the time of the survey and prior use were significantly associated with hair thinning (current users, ≥2 years: OR 1.86; prior users: OR 1.62), but not hair loss. Findings from this study suggest that aromatase inhibitor use is associated with an increased risk of hair loss and hair thinning independent of chemotherapy and age; these side effects are likely due to the substantial decrease in estrogen concentrations resulting from treatment with this drug. Future research should focus on examining these associations in a prospective manner using more detailed and objective measures of hair loss and thinning. [ABSTRACT FROM AUTHOR]

Little is known about the decisions and perspectives of participants undergoing direct-to-consumer genetic testing (DTCGT). The aims of this study were to examine the views, attitudes and decision-making factors of primary care patients regarding DTCGT. Their experience of and reactions to testing also emerged during the study. In this longitudinal, qualitative study, 20 primary care patients participated in DTCGT and individual interviews: (1) prior to testing after the informed consent session, (2) after receiving results, (3) 3 months post-test, and (4) 12 months post-test. Interviews included open-ended questions and all transcripts were analyzed using grounded theory, constant comparison methods. Five key themes emerged from data analysis as participants underwent DTCGT and reflected on their decision over time: (1) limited concerns about DTCGT, (2) motivations for testing, (3) expectations of testing, (4) understanding of results, and (5) impact of testing and results. While a few participants expressed concerns before testing, participants were motivated to test by curiosity, gaining actionable knowledge, and altruism. Most were uncertain of what to expect from DTCGT and needed assistance in understanding results. While many reported testing had no significant impact on them, being relieved or pleased after testing was the most common emotional effect. Notably, a few participants made positive health changes in response to testing. Given the paucity of information about primary care patients and DTCGT, this study adds more in-depth information to the emerging research on how such participants' view, make decisions about, experience and react to DTCGT over time. Because uncertainty remains about the accuracy of DTCGT, the response of primary care patients to this testing requires further investigation. [ABSTRACT FROM AUTHOR]

Purpose: Musculoskeletal pain is a common side effect of aromatase inhibitors (AIs), the adjuvant hormonal treatment of choice for postmenopausal estrogen-receptor-positive breast cancer. Although the pain is usually attributed to the estrogen depletion associated with AIs, not all women on AIs experience these symptoms. Thus, the goal of this study was to examine whether changes in the insulin-like growth factor (IGF) axis were associated with pain among women initiating AI therapy or a comparison group of women without a history of cancer. Methods: Data were analyzed from a cohort study of 52 breast cancer patients for whom AI therapy was planned and 88 women without a history of cancer. Questionnaire data on pain symptoms were collected, and blood was drawn at baseline (prior to AI therapy for patients) and 6 months after baseline. The blood samples were assayed for IGF-1 and IGF-binding protein-3 (IGFBP-3). Results: While results showed no statistically significant changes in any of the measures across time for either the breast cancer or the comparison group, increases in both IGF-1 concentrations and the IGF-1/IGFBP-3 ratio over the first 6 months of AI treatment were significantly associated with the onset or increase in musculoskeletal pain among the breast cancer patients. Associations between IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 ratio and pain were not observed in the comparison group. Conclusions: Although preliminary, findings from this study implicate the IGF axis in the development of AI-associated musculoskeletal pain and represent a first step in developing effective interventions to alleviate this side effect. [ABSTRACT FROM AUTHOR]

Purpose: Sleep-related complaints are common in cancer survivors. Although daytime sleepiness and sleep duration are associated with poor functional status, quality of life, and mortality in the general population, little is known about these issues in long-term cancer survivors. This study examined differences in daytime sleepiness and sleep duration between long-term cancer survivors and non-cancer controls. Methods: Survey data were analyzed from individuals diagnosed with cancer ≥2 years in the past ( n = 1,171, mean age = 64.30, 80.8% white, 22.8% male) and spouse/friends controls ( n = 250, mean age = 60.78, 88.0% white, 64.8% male). Daytime sleepiness was assessed using the Epworth Sleepiness Scale. Associations between sleep-related variables and history of cancer were estimated with multivariable logistic regression, adjusting for potential confounders. Stratified analyses were conducted to identify subgroups of survivors most at risk for sleep problems. Results: Cancer survivors were more likely than controls to report excessive daytime sleepiness (OR = 1.64, 95% CI: 1.07, 2.50). A cancer diagnosis was associated with longer sleep duration among males (OR = 1.25, 95% CI: 1.02, 1.53), but not in females (OR = 0.87, 95% CI: 0.37, 1.05). All other associations were similar regardless of cancer site, histology, time since diagnosis, treatment history, and history of multiple cancers. Conclusions: Disturbances in daytime sleepiness and sleep duration persist among long-term cancer survivors and should be monitored in routine survivorship care. More research is needed to identify cancer survivors who are at increased risk for daytime sleepiness and disturbed sleep duration, as well as to identify causal mechanisms for, and interventions to mitigate, persistent differences. [ABSTRACT FROM AUTHOR]

This study compared type, severity and location of musculoskeletal symptoms and associations with 25-hydroxyvitamin D (25(OH)D) and C-reactive protein (CRP) concentrations between women initiating aromatase inhibitor (AI) therapy and an unexposed comparison group. A 6-month prospective cohort study was conducted, enrolling 100 breast cancer patients prior to initiating AI treatment and an unexposed comparison group of 200 postmenopausal women. Multivariate associations were assessed with generalized linear models. At baseline, 55% of breast cancer patients and 63% of the comparison group reported any musculoskeletal symptoms. Among the unexposed group, prevalence and severity of symptoms remained constant with no statistically significant change over 6 months. Among breast cancer patients, but not unexposed women, the pain severity score significantly increased over the 6 month period for joint ( P < 0.001), muscle ( P = 0.004), and bone pain ( P = 0.01). Women treated with AIs were more likely to report pain in wrists/palms (63% at 6 months) compared to unexposed women (31% at 6 months) ( P < 0.001). 25(OH)D concentrations increased over the study period among breast cancer patients ( P = 0.004). An increase in pain severity and prevalence was observed among breast cancer patients despite an increase in 25 (OH)D concentration. CRP concentrations were not associated with symptoms. Musculoskeletal symptoms are common among postmenopausal women. Breast cancer patients initiating AI treatment were at increased risk for developing new onset and more severe joint, muscle and bone pain compared to unexposed women, with a distinct distribution. AI-associated symptoms were not associated with 25(OH)D or CRP concentrations. [ABSTRACT FROM AUTHOR]

Aromatase inhibitors (AIs), the adjuvant hormonal treatment of choice for postmenopausal estrogen receptor-positive breast cancer, are associated with an increased risk of musculoskeletal symptoms. The underlying cause of the symptoms is often attributed to estrogen depletion, yet all women treated with AIs have low estrogen levels and only a subset develop symptoms. Concentrations of circulating androgens may be mediating factors contributing to these side effects. The purpose of this study was to examine changes in androgen concentrations among women initiating AI therapy and to determine if concentrations are associated with musculoskeletal symptoms. Data were analyzed from a cohort study of 74 breast cancer patients for whom AI therapy was planned. Questionnaire data on symptoms were collected and blood was drawn prior to AI therapy (baseline) and then again at 3 and 6 months after baseline. Blood was assayed for testosterone, androstenedione, dehydroepiandrosterone-sulfate (DHEAS), and sex hormone-binding globulin (SHBG). Free testosterone index (FTI) values were calculated using testosterone and SHBG measurements. The results showed that concentrations of all of the androgens increased over the study period, with statistically significant differences from baseline concentrations observed for the FTI at 3 and 6 months and for DHEAS at 6 months . Additionally, breast cancer patients with new onset or worsening of pain over the study period had a significantly smaller change in mean DHEAS concentration from baseline to 3 months ( P = 0.04) and a marginally significant smaller change in mean DHEAS concentration from baseline to 6 months ( P = 0.1) compared to those who reported no pain at all time points or no worsening of pain across the study period. Changes in testosterone, androstenedione, and the FTI were not associated with the onset or worsening of pain during the study period. Findings from this study suggest that higher DHEAS concentrations are associated with less AI-associated pain and should be further investigated. [ABSTRACT FROM AUTHOR]

The literature has consistently reported no association between low to moderate alcohol consumption and pancreatic cancer; however, a few studies have shown that high levels of intake may increase risk. Most single studies have limited power to detect associations even in the highest alcohol intake categories or to examine associations by alcohol type. We analyzed these associations using 1,530 pancreatic cancer cases and 1,530 controls from the Pancreatic Cancer Cohort Consortium (PanScan) nested case-control study. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression, adjusting for potential confounders. We observed no significant overall association between total alcohol (ethanol) intake and pancreatic cancer risk (OR = 1.38, 95% CI = 0.86-2.23, for 60 or more g/day vs. >0 to <5 g/day). A statistically significant increase in risk was observed among men consuming 45 or more grams of alcohol from liquor per day (OR = 2.23, 95% CI = 1.02-4.87, compared to 0 g/day of alcohol from liquor, P-trend = 0.12), but not among women (OR = 1.35, 95% CI = 0.63-2.87, for 30 or more g/day of alcohol from liquor, compared to none). No associations were noted for wine or beer intake. Overall, no significant increase in risk was observed, but a small effect among heavy drinkers cannot be ruled out. [ABSTRACT FROM AUTHOR]

We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 × 10−11, per-allele odds ratio (OR) 1.26, 95% CI 1.18–1.35) and rs9564966 (P = 5.86 × 10−8, per-allele OR 1.21, 95% CI 1.13–1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 × 10−10, per-allele OR 0.77, 95% CI 0.71–0.84). A single SNP, rs401681 (P = 3.66 × 10−7, per-allele OR 1.19, 95% CI 1.11–1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies. [ABSTRACT FROM AUTHOR]

We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 × 10−8; multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12–1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B. [ABSTRACT FROM AUTHOR]

This study was conducted in an ongoing community-based cohort study to examine the prevalence of non-cancer adverse health conditions among cancer survivors and the association of these conditions with self-rated health and functional status. Data were analyzed from CLUE II, a community-based cohort study in Washington County, Maryland that began in 1989. Cross-sectional comparisons were made between 1,261 cancer survivors and 1,261 age- and gender-matched individuals without a history of cancer. Information on non-cancer adverse health conditions, self-rated health, and activities of daily living was based on self-report. Compared to individuals without a history of cancer, cancer survivors were significantly more likely to report a diagnosis of cardiovascular disease (33.8% versus 29.8%; p = 0.009) and endocrine disease (other than diabetes) (17.0% versus 14.3%; p = 0.02). Further, cancer survivors reporting two or more non-cancer adverse health conditions had a greater likelihood of reporting fair or poor self-rated health (odds ratio (OR) 4.11; 95% confidence interval (95% CI) 3.06, 5.54), and difficulty with at least one activity of daily living (OR 6.03; 95% CI 4.01, 9.05) compared to cancer survivors who did not report other adverse health conditions. Findings from this cross-sectional data analysis indicate that cancer survivors are at increased risk for non-cancer adverse health conditions, which are associated with poorer self-rated health, more interference with normal activities, and functional limitations. Increased attention must be given to the preventive care and treatment of non-cancer adverse health conditions among cancer survivors to decrease non-cancer morbidity and mortality and to maintain and improve quality of life. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between prediagnostic plasma ascorbic acid concentrations and subsequent breast cancer risk in a nested case-control study.Methods: Female volunteer residents of Washington County, MD, donated 14,625 non-fasting blood samples in 1989. Incident breast cancer cases (n = 115) and controls (n = 115) were matched by age, menopausal status at donation, and date and hour of blood donation.Results: Median ascorbic acid concentrations were similar between cases and controls (1.44 mg/dl vs. 1.39 mg/dl. p = 0.78). There was no evidence for a dose-response relationship between higher plasma ascorbic acid concentrations and breast cancer risk [highest vs. lowest fifths: ORadjusted = 0.90, Ptrend = 0.98).Conclusions: Findings from this prospective study do not suggest a protective association between prediagnostic plasma ascorbic acid concentrations and breast cancer risk in the subsequent 5 years of follow-up. [ABSTRACT FROM AUTHOR]

We evaluated the usefulness of a recent measure of drinking water nitrate as a predictor of long-term average nitrate exposure calculated from historic data. Exposure estimates were calculated for 214 study participants who used public water supplies between 1947 and 1980 in Minnesota. Long-term average nitrate was calculated by linking residential histories to historical nitrate data. For recent exposures, we averaged nitrate measurements in 1980, or the next closest year with measurements. The Spearman correlation coefficient for the relationship between the two measures was 0.54 (95% confidence interval [CI] = 0.44-0.63). Agreement was highest among those residing 34 or more years in their town as of 1980 (r[SUBs] = 0.70; 95% CI = 0.55-0.80). These findings suggest that taking into account the study participants' duration of residence may enhance the validity of using a recent measure as an indicator of past exposures. [ABSTRACT FROM AUTHOR]

Experimental and human epidemiologic data suggest a protective role for vitamin D in large bowel cancer. To investigate this association, we conducted a nested case-control study within a Finnish clinical trial cohort. Cases (n = 146) were participants diagnosed with primary adenocarcinoma of the large bowel. Controls were matched (2:1) to cases on age, date of baseline blood draw, and study clinic. Prediagnostic serum levels of the vitamin D metabolites, 25-hydroxyvitamin D (25-OH D), and 1,25-dihydroxyvitamin D (1,25-DIOH D) were used as primary exposure measures. The baseline geometric-mean serum level of 25-OH D was 11.6 percent lower in cases than in controls (12.2 cf 13.8 ug/l, P = 0.01) while serum levels of 1,25-DIOH D did not differ by case-control status. No association was seen between serum levels of 1,25-DIOH D and large bowel cancer risk. However, the estimated relative risk (RR) of large bowel cancer decreased with increasing level of serum 25-OH D and the association was more pronounced for rectal cancer (55 cases; RR by quartile = 1.00, 0.93, 0.77, 0.37; trend P = 0.06). Neither exclusion of early cases nor multivariate adjustment for potential confounders materially altered these estimates. There was no evidence of effect modification by level of 1,25-dihydroxyvitamin D or with other known risk-factors for large bowel cancer. [ABSTRACT FROM AUTHOR]