Real-world experience of second-line axitinib in metastatic renal cell carcinoma: analysis of the Swedish population.

Aim: Assess the time-to-treatment discontinuation (TTD) and overall survival (OS) in a Swedish metastatic renal cell carcinoma (mRCC) nationwide cohort who received second-line axitinib. Methods: Retrospective analysis of 110 patients with mRCC treated with second-line axitinib in Sweden (2012-2019). Patients included in the study received axitinib after mainly first-line sunitinib or pazopanib. Results: The median (95% CI) TTD of patients who received second-line axitinib was 5.2 (3.7-6.1) months with 6 (5.5%) patients still receiving treatment at the time of analysis. Median (95% CI) OS was 12.2 (7.7-14.2) months. Conclusion: The results are consistent with previous findings in mRCC and add to the evidence demonstrating efficacy of second-line axitinib, after failure of a prior anti-angiogenic therapy in a real-world setting.Clinical Trial Registration: NCT04669366 (ClinicalTrials.gov).

[Box: see text].

Identifying Predictors of First-Line Subcutaneous TNF-Inhibitor Persistence in Patients with Inflammatory Arthritis: A Decision Tree Analysis by Indication.

INTRODUCTION: Treatment persistence is a proxy for efficacy, safety and patient satisfaction, and a switch in treatment or treatment discontinuation has been associated with increased indirect and direct costs in inflammatory arthritis (IA). Hence, there are both clinical and economic incentives for the identification of factors associated with treatment persistence. Until now, studies have mainly leveraged traditional regression analysis, but it has been suggested that novel approaches, such as statistical learning techniques, may improve our understanding of factors related to treatment persistence. Therefore, we set up a study using nationwide Swedish high-coverage administrative register data with the objective to identify patient groups with distinct persistence of subcutaneous tumor necrosis factor inhibitor (SC-TNFi) treatment in IA, using recursive partitioning, a statistical learning algorithm. METHODS: IA was defined as a diagnosis of rheumatic arthritis (RA), ankylosing spondylitis/unspecified spondyloarthritis (AS/uSpA) or psoriatic arthritis (PsA). Adult swedish biologic-naïve patients with IA initiating biologic treatment with a SC-TNFi (adalimumab, etanercept, certolizumab or golimumab) between May 6, 2010, and December 31, 2017. Treatment persistence of SC-TNFi was derived based on prescription data and a defined standard daily dose. Patient characteristics, including age, sex, number of health care contacts, comorbidities and treatment, were collected at treatment initiation and 12 months before treatment initiation. Based on these characteristics, we used recursive partitioning in a conditional inference framework to identify patient groups with distinct SC-TNFi treatment persistence by IA diagnosis. RESULTS: A total of 13,913 patients were included. Approximately 50% had RA, while 27% and 23% had AS/uSpA and PsA, respectively. The recursive partitioning algorithm identified sex and treatment as factors associated with SC-TNFi treatment persistence in PsA and AS/uSpA. Time on treatment in the groups with the lowest treatment persistence was similar across all three indications (9.5-11.3 months), whereas there was more variation in time on treatment across the groups with the highest treatment persistence (18.4-48.9 months). CONCLUSIONS: Women have low SC-TNFi treatment persistence in PsA and AS/uSpA whereas male sex and golimumab are associated with high treatment persistence in these indications. The factors associated with treatment persistence in RA were less distinct but may comprise disease activity and concurrent conventional systemic disease-modifying anti-rheumatic drug (DMARD) treatment.

Treatment patterns for advanced non-small cell lung cancer in the US: A systematic review of observational studies.

BACKGROUND: The advent of immunotherapies (I-O) and targeted therapies has transformed the treatment landscape in advanced non-small cell lung cancer (NSCLC). However, adoption of new treatment guidelines and evolving treatment patterns in clinical practice are largely unknown. The aim of this systematic literature review (SLR) was to capture real-world first-line treatment patterns in advanced (staged IIIB-IV) or recurrent NSCLC patients in the US. METHODS: Electronic databases were systematically searched for observational studies published 2012-2020 that reported on adult patients receiving first-line therapy for advanced NSCLC. Included studies were reviewed and treatment patterns were summarized descriptively. RESULTS: Eighteen studies were included. Platinum-doublet (PD) chemotherapy and unspecified chemotherapy regimens were the most commonly used first-line treatments (up to 71% and 96%, respectively). Chemotherapy as monotherapy was mainly utilized in patients ≥65 years. While chemotherapy use was continuously high, I-O became the preferred front-line treatment in 2018 (32.9%). I-O monotherapy was more prevalent among patients with PD-L1 ≥50%, compared to patients with lower levels. First-line use of tyrosine kinase inhibitors and bevacizumab-based therapies was common in 2010 (33.4% and 21.7%, respectively), but gradually declined to <1% in 2018. CONCLUSION: Consistent with the evolving first-line NSCLC treatment landscape in the US, this SLR captures the increasing use of I-O in recent years. While the brief lag in I-O use from the time of authorization may be attributable to an initial resistance to treatment adoption or publication delays, continued use of chemotherapy regimens may reflect an unmet treatment need, which warrants further research.

Treatment Persistence in Patients Cycling on Subcutaneous Tumor Necrosis Factor-Alpha Inhibitors in Inflammatory Arthritis: A Retrospective Study.

INTRODUCTION: Biologic treatments including subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) have greatly improved disease management of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) (collectively inflammatory arthritis, IA). Nevertheless, some patients discontinue their first-line treatment; for them, one option may be a subsequent line of the same treatment class (i.e., cycling). The aim of this study was to assess treatment persistence between first- and second-line therapy in Swedish IA patients cycling on SC-TNFis. METHODS: Using data from the Swedish Health Data Registers, adult IA patients filling prescriptions between May 1, 2010, and October 31, 2016, for a SC-TNFi (adalimumab, etanercept, certolizumab and golimumab) were included. Treatment persistence was derived based on information from filled prescriptions and a 60-day grace period. Unadjusted and adjusted marginal Cox proportional hazards models were fitted to estimate the relative risk of discontinuation across treatment lines, using robust sandwich covariance matrix estimates to account for intrapatient dependence (i.e., multiple treatment lines per patient). The analysis was restricted to the first two lines of treatment. RESULTS: Of the eligible patients, 3181 were identified as cyclers. Among these, most were female (68%), and 46%, 28% and 26% were diagnosed with RA, AS and PsA, respectively. Both the unadjusted and adjusted analyses showed that the relative risk of discontinuing SC-TNFi treatment was significantly lower in second compared to first line (hazard ratio; 0.60 [0.57, 0.63] and HR; 0.59 [0.56, 0.62]). This finding was also consistent across IA indications. CONCLUSIONS: In this study of patients cycling on SC-TNFis in IA, persistence was greater in second- compared to first-line treatment. The finding was consistent across all IA indications. Hence, patients who discontinue their first-line treatment may still benefit from treatment with an alternative SC-TNFi as a second-line therapy in IA.

Health-Care and Societal Costs Associated with Non-Persistence with Subcutaneous TNF-α Inhibitors in the Treatment of Inflammatory Arthritis (IA): A Retrospective Observational Study.

OBJECTIVE: A few studies have suggested that patients with inflammatory arthritis (IA) who remain persistent with subcutaneous TNF-α inhibitors (SC-TNFi) incur lower health care costs than patients who discontinue treatment, whereas data on the impact of non-persistence on indirect costs are largely lacking. Furthermore, existing estimates are based on fixed follow-ups, in relation to treatment initiation, and therefore do not measure costs in direct relation to treatment discontinuation. Therefore, by capturing costs in direct relation to treatment discontinuation, this study aimed to estimate direct and indirect costs associated with non-persistence with SC-TNFis in IA. METHODS: Adult Swedish biologic-naïve IA patients initiating biologic treatment with a SC-TNFi (adalimumab, etanercept, certolizumab or golimumab) between May 6, 2010, and December 31, 2017, were identified in population-based registers with almost complete coverage. IA was defined as a diagnosis of rheumatic arthritis, ankylosing spondylitis/unspecified spondyloarthritis or psoriatic arthritis. Non-persistent patients were matched on propensity score to patients persistent with treatment by at least an additional 12 months. This enabled comparisons of direct healthcare costs and indirect costs for sick leave and disability pension, respectively, 12 months before and 12 months after treatment discontinuation. RESULTS: A balanced cohort of 486 matched pairs was generated. The total direct and indirect costs were significantly higher among non-persistent patients already during the 12 months before index ($20,802 [18,335-23,429] vs. $16,600 [14,331-18,696]). However, while non-persistent patients increased their total direct and indirect costs, persistent patients significantly decreased the same, further widening the difference in costs during the 12-month period after index date ($22,161 [19,754-24,556] vs. $13,465 [11,415-15,729]). CONCLUSIONS: Among biologic-naïve Swedish IA patients treated with SC-TNFis, persistent patients incurred about 40% lower aggregated direct and indirect costs compared to non-persistent patients the year following SC-TNFi discontinuation. This highlights the impact of treatment persistence from an economic viewpoint, adding further aspects to the clinical perspective.

Healthcare-Related Costs Associated with Switching Subcutaneous Tumor Necrosis Factor-α Inhibitor in the Treatment of Inflammatory Arthritis: a Retrospective Study.

INTRODUCTION: Subsequent lines of subcutaneous tumor necrosis factor alpha inhibitor (SC-TNFi) treatment may be well motivated in the management of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)-collectively named inflammatory arthritis (IA). However, the costs associated with switching SC-TNFis are largely unknown. The objective of this retrospective observational study was to explore costs of healthcare resource utilization (HCRU) associated with switching SC-TNFi treatment among biologic-naïve Swedish patients with IA. METHODS: Using population-based register data, adult patients filling prescriptions between May 6, 2010 and December 31, 2014 for an SC-TNFi (adalimumab, etanercept, certolizumab, and golimumab) were included. Patients switching treatment (cyclers) were matched to treatment persistent patients on the basis of propensity score and follow-up time. HCRU-associated costs were captured and compared 12 months before and 12 months after the index date (defined as the date of the switch). RESULTS: A balanced cohort of 594 matched pairs was derived. Prior to the index date, cyclers had significantly higher non-treatment HCRU costs compared to persistent patients ($3815 [3498-4147] vs. $2900; 95%CI [2565-3256]). However, 12 months after the index date, cyclers had significantly increased their non-treatment HCRU costs while persistent patients lowered theirs ($822 [232-1490] vs. $- 313 [- 664-36]). This resulted in a statistically significant difference in difference of $1135 between the groups. CONCLUSIONS: In biologic-naïve patients treated with SC-TNFi for IA, cyclers significantly increased their non-treatment HCRU costs 12 months after switching treatment while persistent patients lowered their costs during the same time period. As these findings indicate that differences in treatment persistence may have an impact on costs, further research utilizing more comprehensive data sources in alternate settings is warranted.

Retrospective observational cohort study on innovation in oncology and progress in survival: How far have we gotten in the two decades of treating patients with advanced non-small cell lung cancer as a single population?

We assessed the impact of new antineoplastic agents on the overall survival (OS) of advanced non-small cell lung cancer (aNSCLC) patients followed up until 2012. Multivariate regression models were run for OS (outcome) and four proxies for innovation (exposure): Index (InnovInd, for SEER-Research data 1973-2012) and three levels of aggregation of Mean Medication Vintage, i.e. Overall (MMVOverall), using data aggregated at the State Level (MMVState), and using patient-level data (MMVPatient) using data from the US captured in SEER-Medicare 1991-2012. We derived Hazard ratios (HR) from Royston-Parmar models and odds ratios (OR) from a logistic regression on 1-year OS. Including 164,704 patients (median age 72 years, 56.8% stage IV, 61.8% with no comorbidities, 37.8% with adenocarcinoma, 22.9% with squamous-cell, 6.1% were censored). One-year OS improved from 0.22 in 1973 to 0.39 in 2012, in correlation with InnovInd (r = 0.97). Ten new NSCLC drugs were approved and 28 more used off-label. Regression-models results indicate that therapeutic innovation only marginally reduced the risk of dying (HROverall = 0.98 [0.98-0.98], HRMMV-Patient = 0.98 [0.97-0.98], and HRMMV-State = 0.98 [0.98-0.98], and slightly improved 1-year survival (ORMMV-Overall = 1.05 95%CI [1.04-1.05]). These results were validated with data from the Swedish National Health Data registers. Until 2013, aNSCLC patients were treated undifferentiated and the introduction of innovative therapies had statistically significant, albeit modest, effects on survival. Most treatments used off-guidelines highlight the high unmet need; however new advancements in treatment may further improve survival.

The value of persistence in treatment with subcutaneous TNF-alpha inhibitors for ankylosing spondylitis.

OBJECTIVE: To estimate the impact of persistence on cost-effectiveness of subcutaneous tumor necrosis factor-α inhibitors (SC-TNFis) from healthcare and societal perspectives in a United Kingdom ankylosing spondylitis (AS) population using a recently published Markov cohort model. METHODS: A recently published cost-effectiveness model developed for a National Institute for health and Care Excellence appraisal was extended to fit the current study; in brief, it is a Markov cohort model where treatment responders continue from the trial period with maintenance SC-TNFi treatment, while non-responders transition to conventional care. Costs and effects were modeled for a hypothetical SC-TNFi with average efficacy and price. Model outcomes included quality-adjusted life-years (QALYs), total direct and indirect lifetime costs, and incremental cost-effectiveness ratios (ICERs). The cost-effectiveness of SC-TNFi persistence was estimated by decreasing the annual discontinuation probability in five percentage point increments from 25 to 5% per annum. RESULTS: From a health care perspective, the ICERs for the modeled discontinuation rates compared to the baseline annual discontinuation rate (25%) ranged between GBP 17,277 and GBP 18,161. From a societal perspective, increased discontinuation rates resulted in decreased total costs and higher QALYs; hence, lower discontinuation rates dominated higher discontinuation rates from a societal perspective. CONCLUSION: In conclusion, this study shows that, all else equal, higher SC-TNFi treatment persistence in AS is cost effective from a health care perspective and dominant from a societal perspective. Hence, all else equal, prescribing the SC-TNFi with the highest persistence may be considered a cost-effective strategy.

Real-world cost-effectiveness of targeted therapy in metastatic renal cell carcinoma in Sweden: a population-based retrospective analysis.

OBJECTIVE: To explore cost-effectiveness of targeted therapies (TTs) in the treatment of metastatic renal cell carcinoma (mRCC) in a real-world context using a nationwide population-based approach. METHODS: Data on patients diagnosed with mRCC between 2002 and 2012 were extracted from Swedish national health data registers. To facilitate comparisons of patients diagnosed before and after TT introduction to the market, three cohorts were derived: pre-TT introduction (preTT), patients diagnosed 2002-2005; early TT introduction (TTi), patients diagnosed 2006-2008; and late TT introduction (TTii), which was limited to patients diagnosed 2009-2010 to ensure availability of total health care resource utilization (HCRU) data. Patients were followed until end of 2012. The value of TTs across cohorts was estimated using mean HCRU costs per life-year (LY) gained. Data on HCRU were obtained through national health registers for dispensed medication and inpatient and outpatient care, and the associated costs were estimated using the Lin method to account for censoring. LYs gained were defined as the difference in mean survival over the study period. RESULTS: The preTT, TTi, and TTii cohorts consisted of 1,366, 1,158, and 806 patients, respectively. Mean survival in years from mRCC diagnosis was 1.45 in the preTT cohort, 1.62 in the TTi cohort, and 1.83 in the TTii cohort. The respective mean total HCRU cost per patient over the study period was US$16,894, US$29,922, and US$30,037. The cost per LY gained per cohort was US$78,656 for TTi vs preTT, US$34,132 for TTii vs preTT, and US$523 for TTii vs TTi. CONCLUSION: Given common willingness-to-pay per LY gained thresholds, this study in a real-world population suggests the use of TTs in the Swedish mRCC population is increasingly cost-effective over time.

Second-line treatment persistence and costs among patients with immune-mediated rheumatic diseases treated with subcutaneous TNF-alpha inhibitors.

The objective of this study was to describe treatment persistence with second-line subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) in patients with immune-mediated rheumatic diseases (IMRDs) in Sweden, and the impact of non-persistence on healthcare costs. This retrospective observational study was based on Swedish national health register data. Adults were identified through filled prescriptions for adalimumab (ADA), etanercept (ETA), certolizumab pegol (CZP) and golimumab (GLM). Persistence was estimated over 3 years for propensity score-matched (PSM) cohorts using non-parametric survival analysis. Unadjusted comparisons of costs comprised specialized outpatient care, inpatient care, and medication. In total, N = 845 patients were identified and three PSM cohorts were generated (GLM vs. ADA, ETA, and CZP, respectively). GLM exhibited higher persistence than ADA over the study period (p = 0.040), and numerically higher persistence than ETA and CZP for 36 and 30 months, respectively. Persistent and non-persistent patients had similar mean total cost at 12 month pre-treatment ($5185 vs. $5064, p = 0.750). During the 12 month post-treatment initiation, persistent patients had lower mean total costs ($4377 vs. $6605), corresponding to a cost difference of $2228 (p < 0.001). In second-line treatment with SC-TNFis for IMRDs in Sweden, GLM exhibited significantly higher persistence than ADA over the course of the study. Similarly, GLM showed numerically higher persistence than ETA and CZP, which is concurrent with results observed in first-line SC-TNFi treatment. Considering the lower healthcare costs for persistent patients, the choice of second-line SC-TNFi among eligible patients may merit careful consideration given its impact on patients and payers.

Persistence and costs with subcutaneous TNF-alpha inhibitors in immune-mediated rheumatic disease stratified by treatment line.

OBJECTIVES: The objectives of this study were to 1) describe and compare treatment persistence with first- and second-line subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), or rheumatoid arthritis (RA) (collectively immune-mediated rheumatic disease) in Sweden and 2) estimate and contrast health care costs in the two groups. METHODS: Patients who initiated their first or second SC-TNFi between May 6 2010 and December 12 2012 were identified from the Prescribed Drug Register. Persistence was estimated using survival analysis. Costs comprised specialized outpatient care, inpatient care, and medication. The persistence analysis was stratified by immune-mediated rheumatic disease diagnosis. RESULTS: A total of 4,903 patients treated with their first and 845 patients treated with their second SC-TNFi were identified. Baseline characteristics differed between the two groups. Therefore, propensity score matching analysis was implemented. Second-line patients were matched to first-line patients, and four cohort pairs (AS, PsA, RA, and all diagnoses combined) were generated. Patients treated with their first SC-TNFi had statistically significant higher persistence than patients treated with their second SC-TNFi in PsA (P=0.036), RA (P=0.048), and all diagnoses combined (P<0.001) but not in AS (P=0.741). Patients who were treated with their second SC-TNFi incurred higher costs than patients treated with their first SC-TNFi. CONCLUSION: Overall, persistence to the first SC-TNFi was higher than persistence to the second SC-TNFi. Furthermore, the second SC-TNFi was associated with higher costs than the first SC-TNFi. Therefore, prescribing the SC-TNFi with the best long-term persistence first may be beneficial.

Treatment persistence among patients with immune-mediated rheumatic disease newly treated with subcutaneous TNF-alpha inhibitors and costs associated with non-persistence.

The main objective of this study was to describe real-world treatment persistence with subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFi) in patients with ankylosing spondylitis, psoriatic arthritis, or rheumatoid arthritis [collectively immune-mediated rheumatic disease, (IMRD)] in Sweden. A secondary objective was to describe potential effects on health care resource utilization (HCRU) cost from non-persistence. Patients were identified through filled prescriptions for adalimumab (ADA), etanercept (ETA), certolizumab pegol (CZP), and golimumab (GLM) between 5/6/2010 and 12/31/2012 from the Swedish Prescribed Drug Register. Persistence was estimated using survival analysis. Costs were derived from HCRU and comprised specialized outpatient care, inpatient care and non-disease-modifying antirheumatic drug medications. A total of 4903 patients were identified (ADA: 1823, ETA: 1704, CZP: 622, GLM: 754). Comparisons over 3 years showed that GLM had significantly higher persistence than ADA (p = 0.022) and ETA (p = 0.004). The mean difference in non-biologic HCRU costs between persistent and non-persistent patients was higher after compared to before the start of biologic therapy. SC-TNFi-naïve IMRD patients initiating treatment with GLM had significantly higher persistence rates than patients initiating treatment with ADA or ETA in Sweden. Furthermore, persistence rates observed in the study were lower than those observed in clinical trials, highlighting the need for an all-party (provider-patient-payer-drug manufacturer) engagement and development of programs to increase persistence rates in clinical practice, thus leading to improved clinical outcomes. In addition, the results of this study indicate that persistence to treatment with SC-TNFi may be associated with cost offsets in terms of non-biologic costs.

Baseline patient characteristics, incidence of CINV, and physician perception of CINV incidence following moderately and highly emetogenic chemotherapy in Asia Pacific countries.

PURPOSE: This paper describes the incidence of chemotherapy-induced nausea and vomiting (CINV) after highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer in six Asia Pacific countries. METHODS: Sequential adult patients naïve to chemotherapy and scheduled to receive at least two cycles of single-day HEC or MEC were enrolled in this prospective observational study. Patients completed the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool on post-chemotherapy days 2 and 6 to record acute-phase (first 24 h) and delayed-phase (days 2-5) CINV. RESULTS: There were 648 evaluable patients (318 HEC, 330 MEC) from Australia (n = 74), China (153), India (88), Singapore (57), South Korea (151), and Taiwan (125). Mean (SD) patient age was 56 (12) and 58% of patients were women; the most common primary cancers were breast (27%), lung (22%), and colon (20%). Overall in cycle 1, complete response (no emesis or rescue antiemetics) was recorded by 69% (95% confidence interval (CI), 66-73) of all evaluable patients, with country percentages ranging from 55 to 78% (p < 0.001). After HEC, no emesis was recorded by 75% and no nausea by 38% of patients. After MEC, 80% had no emesis and 50% no nausea. Acute-phase CINV was better controlled than delayed-phase CINV, and the control of nausea was the lowest of any CINV measure in all phases. In a CINV perception survey, physicians tended to overestimate emesis rate and underestimate nausea rate. CONCLUSIONS: CINV remains a substantial problem, and country-specific information about CINV can be useful in developing strategies to improve outcomes for patients undergoing chemotherapy.

Common variants in human CRC genes as low-risk alleles.

The genetic susceptibility to colorectal cancer (CRC) has been estimated to be around 35% and yet high-penetrance germline mutations found so far explain less than 5% of all cases. Much of the remaining variations could be due to the co-inheritance of multiple low penetrant variants. The identification of all the susceptibility alleles could have public health relevance in the near future. To test the hypothesis that what are considered polymorphisms in human CRC genes could constitute low-risk alleles, we selected eight common SNPs for a pilot association study in 1785 cases and 1722 controls. One SNP, rs3219489:G>C (MUTYH Q324H) seemed to confer an increased risk of rectal cancer in homozygous status (OR=1.52; CI=1.06-2.17). When the analysis was restricted to our 'super-controls', healthy individuals with no family history for cancer, also rs1799977:A>G (MLH1 I219V) was associated with an increased risk in both colon and rectum patients with an odds ratio of 1.28 (CI=1.02-1.60) and 1.34 (CI=1.05-1.72), respectively (under the dominant model); while 2 SNPs, rs1800932:A>G (MSH6 P92P) and rs459552:T>A (APC D1822V) seemed to confer a protective effect. The latter, in particular showed an odds ratio of 0.76 (CI=0.60-0.97) among colon patients and 0.73 (CI=0.56-0.95) among rectal patients. In conclusion, our study suggests that common variants in human CRC genes could constitute low-risk alleles.

Lack of an association between the TGFBR1*6A variant and colorectal cancer risk.

PURPOSE: Recently a common variant of the TGFBR1 gene, TGFBR1*6A, has been proposed to act as a low-penetrance tumor susceptibility allele for colorectal cancer, but data from published studies with individually low statistical power are conflicting. To further evaluate the relationship between TGFBR1*6A and colorectal cancer risk, we have conducted a large case-control study and a meta-analysis of previously published studies. EXPERIMENTAL DESIGN: A total of 1,042 colorectal cancer cases and 856 population controls were genotyped for the TGFBR1*6A polymorphism. Previously published case-control studies of the relationship between TGFBR1*6A and colorectal cancer were identified, and a meta-analysis was conducted. RESULTS: We found no evidence that homozygosity, heterozygosity or carrier status for the TGFBR1*6A allele confers an increased risk of colorectal cancer; respective odds ratios (OR) were 1.05 [95% confidence interval (95% CI), 0.83-1.32], 0.82 (95% CI, 0.34-1.99), and 0.92 (95% CI, 0.74-1.15), respectively. A meta-analysis of our case-control study and seven other studies that provided data on 2,627 colorectal cancer cases and 3,387 controls also yielded no evidence that possession of the TGFBR1*6A allele is associated with an elevated risk of colorectal cancer; pooled estimate of the OR were 1.20 (95% CI, 0.64-2.24) for homozygosity, 1.11 (95% CI, 0.96-1.29) for heterozygosity, and 1.13 (95% CI, 0.98-1.30) for carriers of TGFBR1*6A. CONCLUSION: Current data provide limited support for the hypothesis that sequence variation in TGFBR1 defined by the TGFBR1*6A allele confers an elevated risk of colorectal cancer.

The CHEK2 1100delC variant in Swedish colorectal cancer.

BACKGROUND: The cell cycle checkpoint kinase 2 (CHEK2) 1100delC variant has recently been identified at high frequency in families with both breast and colorectal cancer, suggesting the possible role of this variant in colorectal cancer predisposition. PATIENTS AND METHODS: To evaluate the role of CHEK2 ll00delC among Swedish colorectal cancer patients, the variant frequency was determined in 174 selected familial cases, 644 unselected cases and 760 controls, as well as in l8 families used in the genome-wide linkage analysis, where weak linkage was seen for the region harboring the CHEK2 gene. RESULTS: CHEK2 l100delC was found in 1.15% of familial and in 0.93% of unselected cases, compared to 0.66% of controls, showing no significant difference between groups. One out of 45 familial cases with a family history of breast cancer was shown to be a carrier. The variant was not identified in the 18 families included in the linkage analysis. CONCLUSION: The CHEK2 1100delC was not significantly increased in Swedish colorectal cancer patients, however, in order to determine the role of the variant in colorectal cancer families with the history of breast cancer a larger sample size is needed.