查看更多>>摘要：Abstract Collagens are the main components of extracellular matrix in the tumor microenvironment. Both fibrillar and nonfibrillar collagens are involved in tumor progression. The nonfibrillar network‐forming collagens such as type IV and type VIII collagens are frequently overexpressed in various types of human cancers, which promotes tumor cell proliferation, adhesion, invasion, metastasis and angiogenesis. Studies on the roles of these collagens have shed light on the mechanisms underpinning the effects of this protein family. Future research has to explicit the role of network‐forming collagens with respect to cancer progression and treatment. Herein, we review the regulation of network‐forming collagens expression in cancer; the roles of network‐forming collagens in tumor invasion, metastasis and angiogenesis; and the clinical significance of network‐forming collagens expression in cancer patients.
Amy L. WalzAndrew D. WoodsMarry M. Heuvel‐EibrinkConrad V. Fernandez...
16页
查看更多>>摘要：Abstract The survival of childhood Wilms tumor is currently around 90%, with many survivors reaching reproductive age. Chemotherapy and radiotherapy are established risk factors for gonadal damage and are used in both COG and SIOP Wilms tumor treatment protocols. The risk of infertility in Wilms tumor patients is low but increases with intensification of treatment including the use of alkylating agents, whole abdominal radiation or radiotherapy to the pelvis. Both COG and SIOP protocols aim to limit the use of gonadotoxic treatment, but unfortunately this cannot be avoided in all patients. Infertility is considered one of the most important late effects of childhood cancer treatment by patients and their families. Thus, timely discussion of gonadal damage risk and fertility preservation options is important. Additionally, irrespective of the choice for preservation, consultation with a fertility preservation (FP) team is associated with decreased patient and family regret and better quality of life. Current guidelines recommend early discussion of the impact of therapy on potential fertility. Since most patients with Wilms tumors are prepubertal, potential FP methods for this group are still considered experimental. There are no proven methods for FP for prepubertal males (testicular biopsy for cryopreservation is experimental), and there is just a single option for prepubertal females (ovarian tissue cryopreservation), posing both technical and ethical challenges. Identification of genetic markers of susceptibility to gonadotoxic therapy may help to stratify patient risk of gonadal damage and identify patients most likely to benefit from FP methods.
Ming SunTone Bj?rgeStanley TelekaAnders Engeland...
10页
查看更多>>摘要：Abstract Physical activity (PA) has been associated with a lower risk of some obesity‐related cancers, but the combined association and interaction of PA and body weight on obesity‐related cancer risk is less clear. We examined the association of leisure‐time PA (high/low) and its combination with body mass index (BMI, <25 [low]/≥25 [high] kg/m2) on obesity‐related cancer risk in 570?021 individuals, aged 43?years on average at baseline, in five Scandinavian cohorts. We used Cox regression to calculate hazard ratios of obesity‐related cancers (n?=?19?074) and assessed multiplicative and additive interactions between PA and BMI on risk. High leisure‐time PA, recorded in 19% of the individuals, was associated with a 7% (95% confidence interval [CI] 4%‐10%) lower risk of any obesity‐related cancer compared to low PA, with similar associations amongst individuals with a low and a high BMI (6% [1%‐11%] and 7% [2%‐11%]). High PA was also associated with decreased risks of renal cell (11% [9%‐31%]) and colon cancer (9% [2%‐16%]). When high PA and low BMI were combined, the relative risk reduction for all obesity‐related cancers was 24% (95% CI 20%‐28%); endometrial cancer, 47% (35%‐57%); renal cell cancer, 39% (27%‐51%); colon cancer, 27% (19%‐35%); multiple myeloma, 23% (2%‐40%) and pancreatic cancer, 21% (4%‐35%), compared to low PA‐high BMI. There were no additive or multiplicative interactions between PA and BMI on risk. The result of our study suggests a reduced risk of obesity‐related cancer by leisure‐time PA in both normal weight and overweight individuals, which further decreased for PA and normal weight combined.
Thi Xuan Mai TranSoyeoun KimHuiyeon SongBoyoung Park...
9页
查看更多>>摘要：Abstract Mammographic breast density and body mass index (BMI) are strong risk factors of breast cancer, but few studies have investigated these factors in older women. Our study assessed the association between breast density, BMI and the breast cancer risk among women aged ≥75?years. We included women who underwent breast cancer screening between 2009 and 2014 and were followed up until 2020. Breast density was measured using Breast Imaging Reporting and Data System. BMI was classified into three groups: <23, 23 to <25 and ≥25. Cox proportional hazards models were used to estimate the association of breast density and BMI with breast cancer risk. In 483?564 women, 1885 developed breast cancer. The 5‐year incidence increased with an increase in breast density and BMI. Increase in breast density was associated with an increased breast cancer risk in all BMI categories: among women with BMI <23, those with heterogeneous/extreme density had a 2.98‐fold (95% CI: 2.23‐3.80) increased risk of breast cancer compared to those with entirely fatty breasts. An increase in BMI was associated with increased breast cancer risk in women with the same breast density in all density categories. When the combined associations of breast density and BMI on the risk of breast cancer were considered, women with a BMI ≥25 and heterogeneous/extreme breast density had a 5.35‐fold (95% CI: 4.26‐6.72) increased risk of breast cancer compared to women with a BMI <23 and fatty breasts. Women aged ≥75?years, with dense breasts, regardless of BMI status, might benefit from a tailored screening strategy for early detection of breast cancer.
查看更多>>摘要：Abstract Triaging of women positive for high‐risk human papillomavirus (hrHPV) on self‐collected samples requires a molecular reflex test to avoid recall for cytology or visual tests. We assessed triage performance and predictive value of human gene methylation panel (ZNF671/ASTN1/ITGA4/RXFP3/SOX17/DLX1) alone and with combination of HPV16/18 genotyping in a longitudinal screening study. Out of 9526 women at baseline, 1758 women positive for hrHPV on self‐collected samples followed up yearly were included in the current analysis. Satisfactory risk stratification to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was demonstrated by the methylation panel with an odds ratio (OR) of 11.3 among methylation‐positive women compared to methylation‐negative counterparts. Triaging with methylation panel reduced colposcopy referral rate by 67.2% with sensitivity and specificity of 83.0% and 69.9% to detect CIN2+. The corresponding values for the combining methylation and HPV 16/18 were 96.6% and 58.3%. The cumulative 3‐year incident CIN2+ risk was 6.8% (95% CI: 4.9%‐8.6%) for hrHPV positive women, which was reduced to 4.5% (95% CI: 2.7%‐6.3%) and 2.9% (95% CI: 1.2%‐4.5%) for women negative on methylation triaging alone and negative on the combined strategy. The corresponding risk for women positive for both methylation and HPV 16/18 reached 33.7% (95% CI: 19.0%‐45.8%). Our study demonstrated the satisfactory triage performance and predictive value of the methylation panel, especially in combination with HPV 16/18 genotyping. The substantially lower risk of CIN2+ among the triage negative women over the next 3?years suggests that the interval for repeat HPV test can be safely extended to at least 2?years.
查看更多>>摘要：Abstract A common G risk allele in the melatonin receptor 1B (MTNR1B, rs10830963) gene has been associated with altered melatonin signaling and secretion. Given that melatonin possesses anticancerogenic properties, we hypothesized that breast and prostate cancer risks vary by rs10830963 genotype. A total of 216?702 participants from the UK Biobank without cancer at baseline (aged 56.4?±?8.0?years, 50.79% female) were included. Multivariable Cox regression adjusting for known risk factors for breast or prostate cancer was used to estimate the independent effects of the rs10830963 SNP and chronotype on cancer risk. Over a median follow‐up of 8?years, 2367 (2.15% of women) incidences of breast cancer and 2866 (2.69% of men) incidences of prostate cancer were documented in females and males, respectively. rs10830963 genotype is not associated with cancer risk independently (female Ptrend?=?.103, male Ptrend?=?.281). A late chronotype is associated with breast cancer risk in females (Ptrend?=?.014), but not prostate cancer risk in males (Ptrend?=?.915). Further stratification analysis revealed that the rs10830963 genotype is associated with a breast cancer risk in females with moderate evening chronotype (Ptrend?=?.001) and late chronotype is associated with breast cancer risk in females who carry rs10830963 G risk allele (Ptrend?=?.015). Our study suggests that having a late chronotype might increase the risk of breast cancer among females, while the effect of MTNR1B rs10830963 genotype on breast cancer risk is mediated by chronotype.
Dirk NiekerkGina OgilvieEduardo L. FrancoAnna Gottschlich...
9页
查看更多>>摘要：Abstract While cervix screening using cytology is recommended at 2‐ to 3‐year intervals, given the increased sensitivity of human papillomavirus (HPV)‐based screening to detect precancer, HPV‐based screening is recommended every 4‐ to 5‐years. As organized cervix screening programs transition from cytology to HPV‐based screening with extended intervals, there is some concern that cancers will be missed between screens. Participants in HPV FOr CervicAL Cancer (HPV FOCAL) trial received cytology (Cytology Arm) at 24‐month intervals or HPV‐based screening (HPV Arm) at 48‐month intervals; both arms received co‐testing (cytology and HPV testing) at exit. We investigated the results of the co‐test to identify participants with cervical intraepithelial neoplasia grade 2 or higher (CIN2+) who would not have had their precancer detected if they had only their arm's respective primary screen. In the Cytology Arm, 25/62 (40.3%) identified CIN2+s were missed by primary screen (ie, normal cytology/positive HPV test) and all 25 had normal cytology at the prior 24‐month screen. In the HPV arm, three CIN2+s (3/49, 6.1%) were missed by primary screen (ie, negative HPV test/abnormal cytology). One of these three misses had low‐grade cytology findings and would also not have been referred to colposcopy outside of the trial. Multiple rounds of cytology did not detect some precancerous lesions detected with one round of HPV‐based screening. In our population, cytology missed more CIN2+, even at shorter screening intervals, than HPV‐based screening. This assuages concerns about missed detection postimplementation of an extended interval HPV‐based screening program. We recommend that policymakers consider a shift from cytology to HPV‐based cervix screening.
Sara RenbergYifan ZhangFredrik KarlssonRobert Br?nstr?m...
8页
查看更多>>摘要：Abstract Surgery is the cornerstone of gastrointestinal stromal tumor (GIST) treatment, and adjuvant therapy with imatinib has improved survival for high‐risk tumors. The use of imatinib preoperatively has been increasing, but efficacy and impact on patient outcomes have not been formally investigated. This is a retrospective study from a single‐center cohort of patients diagnosed with GIST and treated with neoadjuvant imatinib at Karolinska University Hospital in Stockholm, Sweden over a 20‐year period. Eighty‐four patients diagnosed with GIST and treated with neoadjuvant imatinib were identified and included. Tumors were located throughout the whole gastrointestinal tract but most frequently in the stomach (n?=?29; 35%) and the small intestine (n?=?30; 36%), followed by the rectum (n?=?12; 14%) and the gastroesophageal junction (n?=?10; 12%). The tumors were large (mean 10.5?cm) and decreased after treatment (mean 7.6?cm). Main indications for neoadjuvant imatinib were tumor size or anatomical location. None of the patients with stomach tumors and four patients with tumors near the gastroesophageal junction underwent gastrectomy. Three patients with tumors in the small intestine underwent pancreaticoduodenectomy, whereas seven patients with rectal tumors underwent rectal amputation. After surgery, 94% (n?=?79) of the tumors had R0‐resection. About one‐fourth experienced local relapse or distant metastasis. In conclusion, neoadjuvant imatinib can reduce tumor size and prevent high morbidity due to more extensive surgery, or at least reduce the extent of the surgery, especially for tumors in the stomach or small intestine.
Michael GuentherStefan BoeckVolker HeinemannJens Werner...
6页
查看更多>>摘要：Abstract Adjuvant chemotherapy has become standard of care for pancreatic ductal adenocarcinoma (PDAC) as it improves patient outcome. However, its clinical meaning in early‐stage, UICC I tumors remains uncertain. We examined the effect of adjuvant therapy on disease‐free survival (DFS) and overall survival (OS) of UICC stage I PDAC patients treated at an academic tertiary care center between 2000 and 2016. Among 124 patients (69 male, 55 female; median age 68?years, range 41‐84?years) with UICC stage I disease, adjuvant therapy improved both DFS (19.8 vs 12.8?months, HR 0.59, 95% CI: 0.37‐0.94, P?=?.03) and OS (40.9 vs 20.3?months, HR 0.54, 95% CI: 0.35‐0.84, P?=?.005). Multivariate analyses and propensity score matching confirmed the prognostic impact of adjuvant therapy independent of localization, differentiation and R‐status. Thus, every patient with UICC I PDAC should receive adjuvant chemotherapy as it may improve outcome significantly. Our findings support the concept of PDAC as systemic disease from early stages on.
NSTL
Wiley