Acute myeloid leukemia incidence following radiation therapy for localized or locally advanced prostate adenocarcinoma

Introduction: The effect of radiation therapy on acute myeloid leukemia incidence among prostate cancer patients has not been sufficiently elucidated despite evidence that acute myeloid leukemia is a consequence of therapeutic radiation in other primary malignancies. Therefore, we investigated the effect of definitive therapy with radiation therapy (external beam radiation therapy [EBRT] or brachytherapy) on acute myeloid leukemia incidence in a population-based cohort of patients with localized or locally advanced prostate cancer. Methods: We utilized the Surveillance, Epidemiology, and End Results database to identify a cohort of men (n = 168,612) with newly diagnosed prostate adenocarcinoma between January 1988 and December 2003. Cox proportional hazard regression was used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of acute myeloid leukemia incidence following definitive therapy with EBRT alone, brachytherapy alone, or surgery alone compared to no definitive therapy (i.e. no EBRT, brachytherapy, or surgery). Results: The cohort yielded 184 acute myeloid leukemia cases during 1,064,820 person-years of follow-up after prostate adenocarcinoma diagnosis. Patients treated with EBRT had a higher adjusted relative risk of developing acute myeloid leukemia than patients treated with brachytherapy or surgery when each therapy group was compared to patients who were not treated with definitive therapy (EBRT: HR = 2.05, 95% CI 1.29, 3.26; brachytherapy: HR = 1.22, 95% CI 0.46, 3.22; surgery: HR = 1.24, 95% CI 0.77, 1.98). Conclusions: Our findings suggest that acute myeloid leukemia incidence is a greater concern for patients treated with EBRT than brachytherapy for localized or locally advanced prostate adenocarcinoma.     

Long-term risk of receiving a total hip replacement in cancer patients

Aim: To investigate whether cancer patients have an increased risk of receiving a total hip replacement compared to the standard population of Norway. Materials and methods: By linking of The Cancer Register of Norway and The Norwegian Arthroplasty Register we obtained information on cancer diagnoses (type, date of diagnosis), total hip arthroplasties and date of death for all patients living in Norway. This includes 741,901 patients categorized into three groups: 652,197 patients with at least one cancer diagnosis but no hip arthroplasties, 72,469 patients with at least one hip arthroplasty but no cancer diagnosis and 17,235 patients who have at least one cancer diagnosis and at least one hip arthroplasty. Within this latter group, 8563 individuals had been diagnosed with cancer prior to a total hip arthroplasty. Statistical methods applied in this study were Cox interval censored regression models and standardized incidence ratios (SIR). Results: Cancer patients had a slightly increased risk of receiving a total hip arthroplasty compared to the Norwegian population (SIR = 1.15 (95% CI, 1.12–1.17)). For primary tumours located cranially to the pelvic area there was no significant increase in risk for hip arthroplasty. An exception was breast cancer (SIR = 1.13 (95% CI 1.08–1.18)). Cancer located in the pelvic region (SIR = 1.20 (95% CI 1.16–1.24)), malignant lymphoma (SIR = 1.30 (95% CI 1.15–1.46)) and leukaemia (SIR = 1.17 (95% CI 1.01–1.34)) had an increased risk for receiving a total hip arthroplasty. Conclusion: Cancer survivors, mainly those with pelvic and lympho-hematological malignancies, have a small statistically significant increase in risk for receiving total hip arthroplasty.     

Mortality and incidence of new primary cancers in men with prostate cancer: A Danish population-based cohort study

Background: Prostate cancer (PC) survivors may have an increased risk of new primary cancers (NPCs) due to shared risk factors or PC-directed treatments. Methods: Using Danish registries, we conducted a cohort study of men with (n = 30,220) and without PC (n = 151,100) (comparators), matched 1:5 on age and PC diagnosis/index date. We computed incidence rates of NPCs per 10,000 person years (PY) and associated 95% confidence intervals (CI), and used Cox proportional hazards regression to compute hazard ratios (HRs) and 95%CI, adjusting for comorbidities. In order to obviate any impact of shorter survival among prostate cancer patients, we censored comparator patients when the matched prostate cancer patient died or was censored. Results: Follow-up spanned 113,487 PY and 462,982 PY in the PC and comparison cohorts, respectively. 65% of the cohorts were aged >70 years at diagnosis. Among PC patients, 51% had distant/unspecified stage, and 63% had surgery as primary treatment. The PC cohort had lower incidence of NPCs than their comparators. The adjusted HR of NPC among men with PC versus the comparators was 0.84 (95%CI = 0.80, 0.88). Lowest HRs were among older men, those with distant stage, and were particularly evident for cancers of the brain, liver, pancreas, respiratory, upper gastrointestinal, and urinary systems. Conclusions: We find no evidence of an increased risk of NPCs among men with PC. The deficit of NPCs among men with PC may be a true effect but is more likely due to lower levels of risk factors (e.g., smoking) in PC patients versus comparators, clinical consideration of cancers at new organs as metastases rather than new primaries, or under-recording/under-reporting of NPCs among PC patients.     

Recreational physical activity and risk of papillary thyroid cancer among women in the California Teachers Study

Purpose: Little is known about the relationship between physical activity and thyroid cancer risk, and few cohort data on this association exist. Thus, the present study aimed to prospectively examine long-term activity and risk of papillary thyroid cancer among women. Methods: 116,939 women in the California Teachers Study, aged 22–79 years with no history of thyroid cancer at cohort entry, were followed from 1995–1996 through 2009; 275 were diagnosed with invasive papillary thyroid cancer. Cox proportional-hazards regression provided relative risk (RR) estimates and 95% confidence intervals (CI) for associations between thyroid cancer and combined strenuous and moderate recreational physical activity both in the long-term (high school through age 54 years or current age if younger than 54 years) and recently (during the three years prior to joining the cohort). Results: Overall, women whose long-term recreational physical activity averaged at least 5.5 MET-hours/week (i.e. were active) had a non-significant 23% lower risk of papillary thyroid cancer than inactive women (RR = 0.77, 95% CI: 0.57, 1.04). RR estimates were stronger among normal weight or underweight women (body mass index, BMI < 25.0 kg/m², trend p = 0.03) than among overweight or obese women (trend p = 0.35; homogeneity-of-trends p = 0.03). A similar pattern of risk was observed for recent activity (BMI < 25 kg/m², trend p = 0.11; BMI ≥ 25 kg/m², trend p = 0.16; homogeneity-of-trends p = 0.04). Associations for long-term activity did not appear to be driven by activity in any particular life period (e.g. youth, adulthood). Conclusions: Long-term physical activity may reduce papillary thyroid cancer risk among normal weight and underweight women.     

Antihypertensive medications and survival in patients with cancer: A population-based retrospective cohort study

Background: The association between antihypertensive medications and survival in cancer patients remains unclear. Objectives: To explore the association between classes of antihypertensive drugs and survival in cancer patients. Methods: Provincial Cancer Registry data was linked with a Provincial Drug Program Information Network (DPIN) for patients with lung (n = 4241), colorectal (n = 3967), breast (n = 4019) or prostate (n = 3355) cancer between the years of 2004 and 2008. Cox regression analyses were used to compare survival of patients using beta blockers (BBs), angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARB), calcium channel blockers (CCBs) or thiazide diuretics (TDs) to survival of patients who did not use any of these antihypertensive drugs. Survival of patients using only one class of antihypertensive drugs were compared to each other, with BBs as the reference class. Results: Compared to the antihypertensive drug non-user cohort, BBs had no effect on survival for any of the cancers. ACEi/ARBs use was weakly associated with increased deaths for breast cancer (HR: 1.22, 95% CI: 1.04–1.44) and lung cancer (HR: 1.11, 95% CI: 1.03–1.21) patients. Deaths were also increased with CCB use in patients with breast cancer (HR: 1.22, 95% CI: 1.02–1.47) and with TD use in lung cancer patients (HR: 1.1, 95% CI: 1.01–1.19). There was strong evidence (p-value <0.0001) of an increase in deaths with TD use for colorectal (HR: 1.28, 95% CI: 1.15–1.42), and prostate (HR 1.41, 1.2–1.65) cancer patients. When including only antihypertensive drug users prescribed one drug class, lung cancer patients receiving CCBs had improved survival compared to BBs (HR 0.79, 95% CI: 0.64–0.98). Conclusions: Some classes of antihypertensive agents are associated with a decreased survival in certain cancers. The decrease could be due to more comorbidities in antihypertensive drug users. However, CCB use was associated with improved survival in lung cancer patients.     

Glutathione S-transferase polymorphisms and survival in African-American and White colorectal cancer patients

Background: Glutathione S-transferase (GST) enzymes are involved in electrophile detoxification. The authors investigated the association between GST genotype and survival in a racially diverse, population-based cohort of colorectal cancer (CRC) patients followed for a median of 9.6 years. Methods: Interviews were conducted with 315 African-American and White CRC patients in Connecticut, 1987–1991. Tumor tissue (n = 197) was later retrieved from hospital of diagnosis and assayed using multiplex PCR (GSTM1 and GSTT1) and PCR and RFLP analysis (GSTP1). Cox proportional hazards models provided adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: Individuals with Ile/Val or Val/Val GSTP1 genotypes had a decreased risk of death (multivariate adjusted HR = 0.72, 95% CI: 0.48, 1.09) relative to those with wild type (Ile/Ile). Among those who received chemotherapy, this benefit was more pronounced (HR = 0.35, 95% CI: 0.16, 0.79); the interaction of reduced function GSTP1 genotype and chemotherapy was significant (P = 0.05). GSTM1 and GSTT1 genotype were not associated with survival. GSTM1, GSTT1, and GSTP1 genotype did not vary by race and did not contribute significantly to the survival disadvantage observed in African-Americans. Conclusions: In summary, GSTP1 genotype may play a role in CRC survival in African-Americans and Whites, particularly among those who receive chemotherapy.     

Birth weight and subsequent risk of cancer

Background: We aimed to determine the association between self-reported birth weight and incident cancer in the Women's Health Initiative Observational Study cohort, a large multiethnic cohort of postmenopausal women. Methods: 65,850 women reported their birth weight by category (<6 lbs, 6–7 lbs 15 oz, 8–9 lbs 15 oz, and ≥10 lbs). All self-reported, incident cancers were adjudicated by study staff. We used Cox proportional hazards regression to estimate crude and adjusted hazard ratios (aHR) for associations between birth weight and: (1) all cancer sites combined, (2) gynecologic cancers, and (3) several site-specific cancer sites. Results: After adjustments, birth weight was positively associated with the risk of lung cancer (p = 0.01), and colon cancer (p = 0.04). An inverse trend was observed between birth weight and risk for leukemia (p = 0.04). A significant trend was not observed with breast cancer risk (p = 0.67); however, women born weighing ≥10 lbs were less likely to develop breast cancer compared to women born between 6 lbs-7 lbs 15 oz (aHR 0.77, 95% CI 0.63, 0.94). Conclusion: Birth weight category appears to be significantly associated with the risk of any postmenopausal incident cancer, though the direction of the association varies by cancer type.     

Breast cancer detection risk in screening mammography after a false-positive result

Background: False-positives are a major concern in breast cancer screening. However, false-positives have been little evaluated as a prognostic factor for cancer detection. Our aim was to evaluate the association of false-positive results with the cancer detection risk in subsequent screening participations over a 17-year period. Methods: This is a retrospective cohort study of 762,506 women aged 45–69 years, with at least two screening participations, who underwent 2,594,146 screening mammograms from 1990 to 2006. Multilevel discrete-time hazard models were used to estimate the adjusted odds ratios (OR) of breast cancer detection in subsequent screening participations in women with false-positive results. Results: False-positives involving a fine-needle aspiration cytology or a biopsy had a higher cancer detection risk than those involving additional imaging procedures alone (OR = 2.69; 95%CI: 2.28–3.16 and OR = 1.81; 95%CI: 1.70–1.94, respectively). The risk of cancer detection increased substantially if women with cytology or biopsy had a familial history of breast cancer (OR = 4.64; 95%CI: 3.23–6.66). Other factors associated with an increased cancer detection risk were age 65–69 years (OR = 1.84; 95%CI: 1.67–2.03), non-attendance at the previous screening invitation (OR = 1.26; 95%CI: 1.11–1.43), and having undergone a previous benign biopsy outside the screening program (OR = 1.24; 95%CI: 1.13–1.35). Conclusion: Women with a false-positive test have an increased risk of cancer detection in subsequent screening participations, especially those with a false-positive result involving cytology or biopsy. Understanding the factors behind this association could provide valuable information to increase the effectiveness of breast cancer screening.     

Does night work increase the risk of breast cancer? A systematic review and meta-analysis of epidemiological studies

Objective: To conduct a systematic review, with meta-analysis, of studies assessing the association between night work and the risk of breast cancer, using available epidemiological evidence. Method: Relevant studies were identified by searching several databases and the reference lists of retrieved articles. We combined the relative risks (RR) from individual studies using a random-effects model. Subgroup analysis was carried out as the data showed statistically significant heterogeneity. Results: Thirteen studies consisting of eight case–control studies and five cohort studies were included in the analysis. In the combined analysis of all studies, night work was associated with an increased risk for breast cancer (RR = 1.20, 95%CI = 1.08–1.33). The higher-quality studies showed a similar finding with a pooled RR of 1.40 (95%CI = 1.13–1.73). Both case–control studies (RR = 1.32, 95%CI = 1.17–1.50) and cohort studies (RR = 1.08, 95%CI = 0.97–1.21) showed a positive association between night work and the risk of breast cancer. No publication bias was found either from Begg's funnel plot (P = 0.086) or the Egger's test (P = 0.107). Additional well-conducted and large-scale epidemiological studies are needed.     

Breast cancer susceptibility loci in association with age at menarche,age at natural menopause and the reproductive lifespan

Background: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Some of these loci have unknown functional significance and may mediate the effects of hormonal exposures on breast cancer risk. We examined relationships between breast cancer susceptibility variants and menstrual/reproductive factors using data from two population-based studies. Methods: The first analysis was based on a sample of 1328 women age 20–74 who participated as controls in a case–control study of breast cancer conducted in three U.S. states. We evaluated the associations between age at menarche, age at natural menopause and the reproductive lifespan with 13 previously identified breast cancer variants. Associations were also examined with a genetic score created as the sum of at-risk alleles across the 13 variants. For validation, significant results were evaluated in a second dataset comprised 1353 women age 43–86 recruited as part of a cohort study in Wisconsin. Results: Neither the genetic score nor any of the 13 variants considered individually were associated with age at menarche or reproductive lifespan. Two SNPs were associated with age at natural menopause; every increase in the minor allele (A) of rs17468277 (CASP8) was associated with a 1.12 year decrease in menopause age (p = 0.02). The minor allele (G) of rs10941679 (5p12) was associated with a 1.01 year increase in age at natural menopause (p = 0.01). The results were not replicated in the validation cohort (B = −0.61, p = 0.14 and B = −0.01, p = .0.98, respectively). Conclusions: The evaluated variants and reproductive experiences may work through separate pathways to influence breast cancer risk.     

Effects of polymorphisms in translesion DNA synthesis genes on lung cancer risk and prognosis in Chinese men

PurposeTranslesion DNA synthesis (TLS) plays an important role in promoting replication through DNA lesions. Genetic polymorphisms in TLS genes may have potential roles in lung cancer development in humans.MethodsWe evaluated the association between genetic variants in six TLS genes and the risk and survival of lung cancer in a case–control study in China. Included in the study are 224 lung cancer patients and 448 healthy controls.ResultsCarriers of the G allele of POLκ rs5744724 had significantly reduced risk of lung cancer (odds ratio (OR) = 0.62, 95% confidence interval (CI): 0.44–0.89), comparing with those carrying the C allele, and the AA genotype of PCNA rs25406 was also associated with significantly decreased cancer risk compared with the major homozygote alleles (OR = 0.47, 95% CI: 0.25–0.86). Haplotype analysis showed that subjects with the POLκ C-G (rs5744533–rs5744724) haplotype had decreased risk of lung cancer (OR = 0.69, 95% CI: 0.49–0.98), comparing with those carrying the C-C haplotype. Besides, the heterozygote of REV1 rs3087386 and rs3792136 were independent prognostic factors for lung cancer survival with hazard radio (HR) 1.54 (95% CI: 1.12–2.12) and 1.44 (95% CI: 1.06–1.97) respectively.ConclusionsOur findings suggested that genetic variants in POLκ and PCNA genes may play roles in the susceptibility of lung cancer, and REV1 gene may have roles in lung cancer survival in Chinese men.     

Cancer mortality and occupational exposure to aromatic amines and inhalable aerosols in rubber tire manufacturing in Poland

Aim: Most data on carcinogenic risk in the rubber industry are based on data from Western countries. This study assessed cancer risks in a retrospective cohort in a Polish tire manufacturing plant, relying on quantified exposure to inhalable aerosols and aromatic amines instead of job titles or external comparisons. Methods: Cumulative exposure for all exposures was assigned to cohort members based on estimates from a company-specific JEM. Cancer risks associated with cumulative exposure adjusted for co-exposures, gender and year of birth were calculated. Results: Exposure levels were higher for women than for men. Aromatic amine exposure was significantly associated with increased urinary bladder cancer risk (RR = 7.32–8.27), depending on exposure level, and prostate cancer at low levels only (RR = 5.86). In women, increased risks were found for all cancers (RR = 2.50) and of the digestive organs and peritoneum (RR = 4.54) at low level only, while an exposure-response association with breast cancer risk was found. Inhalable aerosol exposure was associated with cancers of the liver and intrahepatic bile ducts in a dose-dependent manner, while dose-dependent reduced risks were found for respiratory cancers (most notably the larynx) and cancer of the colon. Conclusions: Increased risks for specific cancer sites in this rubber plant were similar to Western Europe and the US. However, several cancer risks were gender-specific which could relate to higher exposure levels in women or to differences in exposures to chemicals not assessed in this study.     

Smoking and other risk factors for pancreatic cancer: A cohort study in men in Lithuania

Background: Cancer of the pancreas is a relatively rare, but highly fatal cancer worldwide. Cigarette smoking has been recognized as an important risk factor, but the relation to other potential determinants is still inconsistent. We investigated the association between different lifestyle, biological and anthropometric factors and the risk of pancreatic cancer in a prospective population-based cohort study from Kaunas, Lithuania. Methods: Our study included 7132 urban men initially free from any diagnosed cancer, followed for up to 30 years. 77 incident cases of pancreatic cancer were identified. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Results: Compared to never smokers, current smokers had a significantly increased risk of pancreatic cancer, HR was 1.79 (95% CI 1.03–3.09) after adjustment for age, body mass index, education and alcohol consumption. Among smokers, a significant association with higher smoking intensity was shown (≥20 cigarettes/day: HR = 2.60; 95% CI 1.42–4.76, P_trend = 0.046). We also observed a significantly increased risk for ≥30 pack-years of smoking (HR = 2.24; 95% CI 1.12–4.49, P_trend = 0.16) and for age at starting smoking <18 years (HR = 2.29; 95% CI 1.11–4.70, P_trend = 0.43) as compared to never smokers. Alcohol consumption, body mass index and total cholesterol level were not significantly associated with pancreatic cancer. Conclusions: Smoking significantly increases pancreatic cancer incidence and its high prevalence in Lithuania may partly explain high incidence of the disease. No convincing evidence was found that alcohol consumption, body mass index or serum cholesterol level were associated with pancreatic cancer risk, although the assessment was limited by the lack of statistical power.     

Lymphohaematopoietic malignancies in Scottish military veterans: Retrospective cohort study of 57,000 veterans and 173,000 non-veterans

BackgroundLymphohaematopoietic malignancies are common in the general population. There have been concerns that military service may be associated with increased risk as a result of occupational exposures. To date, few studies have demonstrated an increased risk, although a disability pension is payable to veterans who were present at nuclear tests and who develop leukaemia (other than chronic lymphocytic leukaemia). The aim of the study was to utilise data from the Scottish Veterans Health Study to examine the risk of lymphohaematopoietic malignancy following military service in a large national cohort of veterans.MethodsRetrospective cohort study of 57,000 veterans and 173,000 non-veterans born between 1945 and 1985 matched for age, sex and area of residence, adjusted for areal deprivation and followed up for up to 30 years, using Cox proportional hazard models to compare the risk of lymphohaematopoietic malignancy overall, by diagnosis and by sex and birth cohort.ResultsWe found no statistically significant difference in risk between veterans and non-veterans either for all leukaemias (Cox proportional hazard ratio 1.03, 95% confidence intervals 0.84–1.27, p = 0.773), Hodgkin lymphoma (hazard ratio 1.19, 95% confidence intervals 0.87–1.61, p = 0.272) or for non-Hodgkin lymphoma (hazard ratio 0.86, 95% confidence intervals 0.71–1.04, p = 0.110).ConclusionOur findings provide reassurance that service in the UK Armed Forces is not associated with increased risk of lymphohaematopoietic malignancy.     

UDP-glucuronosyltransferase 2B17 genotype and the risk of lung cancer among Austrian Caucasians

Background: The enzyme uridine diphospho glucuronosyltansferase 2B17 (UGT2B17) glucuronidates several endogenous and exogenous compounds, including carcinogens from tobacco smoke like 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanl (NNAL). UGT2B17 shows a remarkable copy number variation (CNV) and an association between deletion genotype and increased risk of lung adenocarcinoma in women has been previously reported. Methods: We investigated the UGT2B17 CNV by PCR in 453 Austrian lung cancer patients and in 449 healthy donors and analyzed the impact on lung cancer susceptibility and outcome. Results: Copy numbers of UGT2B17 were 44.4% (+/+), 42.2% (+/?) and 13.5% (?/?) in lung cancer patients and 43.0% (+/+), 46.3% (+/?) and 10.7% (?/?) among healthy donors. The null genotype was not significantly more frequent among women with adenocarcinoma compared to healthy women (p = 0.59). There was no association with overall survival (p = 0.622) and no significant sex-associated (p = 0.423) or histology-related impact on development of lung cancer. Conclusion: UGT2B17 deletion genotype was not associated with a significant risk for lung cancer development or outcome in our Central European patient cohort. Our study indicates that UGT2B17 is not a crucial factor in lung carcinogenesis among Caucasians and shows the importance of investigating such markers in large cohorts from different populations.     

Characteristics and outcomes of patients with Ewing sarcoma over 40 years of age at diagnosis

Background: The peak incidence of Ewing sarcoma (EWS) is in adolescence, with little known about patients who are ≥40 years at diagnosis. We describe the clinical characteristics and survival of this rare group. Methods: This retrospective cohort study utilized the Surveillance Epidemiology and End Results database. 2780 patients were identified; including 383 patients diagnosed ≥40 years. Patient characteristics between age groups were compared using chi-squared tests. Survival from diagnosis to death was estimated via Kaplan–Meier methods, compared with log-rank tests, and modeled using multivariable Cox methods. A competing risks analysis was performed to evaluate death due to cancer. Results: Patients ≥40 years of age were more likely to have extra-skeletal tumors (66.1% vs. 31.7%; p < 0.001), axial tumors (64.0% vs. 57.2%; p = 0.01), and metastatic disease at diagnosis (35.5% vs. 30.0%; p = 0.04) compared to younger patients. Five-year survival for those age ≥40 and age <40 were 40.6% and 54.3%, respectively (p < 0.0001). A Cox multivariable model controlling for differences between groups confirmed inferior survival for older patients (hazard ratio for death of 2.04; 95% CI 1.63–2.54; p < 0.0001); though treatment data were unavailable and not controlled for in the model. A competing risks analysis confirmed increased risk of cancer-related death in older patients. Conclusion: Patients ≥40 years at diagnosis with EWS are more likely to have extra-skeletal tumors, metastatic disease, and axial primary tumors suggesting a difference in tumor biology. Independent of differences in these characteristics, older patients also have a lower survival rate.     

Diabetes,metformin use,and colorectal cancer survival in postmenopausal women

Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study. Methods: 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n = 84); women with diabetes with no metformin use (n = 128); and women without diabetes (n = 1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40–1.38, p = 0.67) and to women without diabetes (HR 1.00; 95% CI 0.61–1.66, p = 0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38–1.55, p = 0.47) and for overall survival was 0.86 (95% CI 0.49–1.52; p = 0.60). Conclusions: In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.     

Surveillance,Epidemiology, and End Results-based analysis of the impact of preoperative or postoperative radiotherapy on survival outcomes for T3N0 rectal cancer

Purpose: Preoperative chemoradiation has been established as standard of care for T3/T4 node-positive rectal cancer. Recent work, however, has called into question the overall benefit of radiation for tumors with lower risk characteristics, particularly T3N0 rectal cancers. We retrospectively analyzed T3N0 rectal cancer patients and examined how outcomes differed according to the sequence of treatment received. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to analyze T3N0 rectal cancer cases diagnosed between 1998 and 2008. Treatment consisted of surgery alone (No RT), preoperative radiation followed by surgery (Neo-Adjuvant RT), or surgery followed by postoperative radiation (Adjuvant RT). Demographic and tumor characteristics of the three groups were compared using t-tests for the comparison of means. Survival information from the SEER database was utilized to estimate cause-specific survival (CSS) and to generate Kaplan–Meier survival curves. Multivariate analysis (MVA) of features associated with outcomes was conducted using Cox proportional hazards regression models with Adjuvant RT, Neo-Adjuvant RT, No RT, histological grade, tumor size, year of diagnosis, and demographic characteristics as covariates. Results: 10-Year CSS estimates were 66.1% (95% CI 62.3–69.6%; P = 0.02), 73.5% (95% CI 68.9–77.5%; P = 0.02), and 76.1% (95% CI 72.4–79.4%; P = 0.02), for No RT, Neo-Adjuvant RT, and Adjuvant RT, respectively. On MVA, Adjuvant RT (HR = 0.688; 95% CI, 0.578–0.819; P < 0.001) was associated with significantly decreased risk for cancer death. By contrast, Neo-Adjuvant RT was not significantly associated with improved cancer survival (HR = 0.863; 95% CI, 0.715–1.043; P = 0.127). Conclusion: Adjuvant RT was associated with significantly higher CSS when compared with surgery alone, while the benefit of Neo-Adjuvant RT was not significant. This indicates that surgery followed by Adjuvant RT may still be an important treatment plan for T3N0 rectal cancer with potentially significant survival advantages over other treatment sequences.     

Do adipokines underlie the association between known risk factors and breast cancer among a cohort of United States women?

Introduction: Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970s and followed for up to 25 years. Methods: Adiponectin, absolute plasminogen activator inhibitor-1 (aPAI-1), and resistin were measured by a multiplex immunoassay. Sex hormones were available for 67 cases and 67 controls. Results: Among controls, we found that lower levels of adiponectin and higher levels of aPAI-1 were correlated with increasing levels of estradiol (Spearman r = ?0.26, p-value = 0.033; r = 0.42, p = 0.0003), decreasing levels of sex hormone binding globulin (r = 0.38, p = 0.0013; r = ?0.32, p = 0.0076), and increasing body mass index (BMI) (r = ?0.31, p =  < 0.0001; r = 0.39, p =  < 0.0001). Hormones were not associated with resistin. Among the relatively small percentage of women using postmenopausal hormones at the time of blood collection (13.7%), aPAI-1 levels were higher than in non-users (p = 0.0054). Breast cancer risk was not associated with circulating levels of adiponectin (age-adjusted p for linear trend = 0.43), aPAI-1 (p = 0.78), or resistin (p = 0.91). The association was not confounded by BMI, parity, age at first full-term birth, age at menopause, current postmenopausal hormone use, and circulating sex steroid hormones. Furthermore, adipokine associations were not modified by BMI (p > 0.05). The lack of association with risk may be due to measurement error of the laboratory assays. Discussion: lower levels of adiponectin and higher levels of aPAI-1 measured in prospectively-collected serum from postmenopausal women were associated with increasing BMI but not breast cancer risk.