First-degree Family History Of Cancer Research Articles

Access to information and oncofertility consultation for young women with breast cancer: a population-based study

Non-menopausal women with breast cancer treated with chemotherapy are at intermediate risk of post-treatment amenorrhea and decreased fertility. Although they should receive appropriate information, studies until now show that this is inadequate. We investigated the proportion of women who received information about this risk during the pre-treatment consultation, and those who received an oncofertility consultation to preserve their gametes. We also analysed the medical and non-medical factors influencing the transmission of information to patients and their uptake of oncofertility consultations. We included women aged 18–40 years treated with chemotherapy for breast cancer between 2012 and 2017 in the Midi-Pyrénées region (ca. 3 million inhabitants), France. Studied variables were included in a multilevel model. Among the 575 women, 41% of the women received information and 28% received an oncofertility consultation. These two steps on the care pathway were significantly influenced by the type of care structure, the woman's age, her parity at the time of diagnosis, and the metastatic status of the cancer. Female oncologist gender was significantly associated with higher transmission rate. We found no association between neoadjuvant chemotherapy status, level of deprivation (EDI), triple-negative status, marital status, and first-degree family history of cancer and information transmission or uptake of oncofertility consultation. Our study shows that not enough women are informed and have recourse to an oncofertility consultation. Despite a legal obligation, the health care system does not offer the necessary conditions for access to oncofertility care.

Key risk factors for the relative and absolute 5‐year risk of cancer to enhance cancer screening and prevention

BackgroundThis study identifies populations who may benefit most from expanded cancer screening.MethodsTwo American Cancer Society prospective cohort studies, Cancer Prevention Study‐II Nutrition Cohort and Cancer Prevention Study‐3, were used to identify the risk factors associated with a > 2% absolute risk of any cancer within 5 years. In total, 429,991 participants with no prior personal history of cancer were followed for cancer for up to 5 years. Multivariable Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for association. By using these hazard ratios, individualized coherent absolute risk estimation was used to calculate absolute risks by age.ResultsOverall, 15,226 invasive cancers were diagnosed among participants within 5 years of enrollment. The multivariable‐adjusted relative risk of any cancer was strongest for current smokers compared with never‐smokers. In men, alcohol intake, family history of cancer, red meat consumption, and physical inactivity were also associated with risk (p < .05). In women, body mass index, type 2 diabetes, hysterectomy, parity, family history of cancer, hypertension, tubal ligation, and physical inactivity were associated (p < .05). The absolute 5‐year risk exceeded 2% among nearly all participants older than 50 years and among some participants younger than 50 years, including current or former smokers (<30 years since quitting) and long‐term nonsmokers with a body mass index >25 kg/m2 or a first‐degree family history of cancer. The absolute 5‐year risk was as high as 29% in men and 25% in women.ConclusionsOlder age and smoking were the two most important risk factors associated with the relative and absolute 5‐year risk of developing any cancer.

Genomic profile by liquid biopsy of Peruvian patients with lung cancer.

e15027 Background: The optimal treatment of advanced NSCLC patients is currently led by genomic profiling with the goal of detecting actionable mutations with an approved targeted therapy. However, tissue DNA samples are not always available to perform this assays. In this context, liquid biopsy has emerged as a valuable tool for providing the best treatment option. Methods: Retrospective study held at Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima - Peru, between January 2019 and September 2021 to assess the genomic profile of 190 newly diagnosed advanced NSCLC patients through liquid biopsy. Blood samples were profiled with the FoundationOne Liquid Biopsy assay. We describe frequency of pathogenic and targetable genetic alterations, as well as the survival outcomes. Genomic and clinical data were recorded from clinical files. Results: The median age was 63 years (26-90), 66.3% were women, 15.3% smokers, 26.3% had exposure to biomass, 22.6% had a first-degree family history of cancer. The most frequent histological type was adenocarcinoma (86.8%). Regarding genomic profile, 183 patients (96.3%) had at least one pathogenic genetic alteration, the most frequent altered genes were TP53 (54.7%), EGFR (50.5%), DNMT3A (17.9%), KRAS (9.5%) and NF1 (6.8%). 116 patients (61%) had a targetable mutation: EGFR Ex19del/ins (27.4%), EGFR L858R/L861Q (17.9%), ALK rearrangements (5.8%), BRAF V600E (3.2%), RET fusions (1.6%), METex14 skipping (1.6%), KRAS G12C (1.6%), ROS 1 (1.1%), and NTRK (0.5%). Of these, 71 patients (65.5%) were able to access target therapy. For the latter, estimated median PFS and OS were 14.0 months (9.3 – 18.6) and 17.8 months (8.2 – 27.4), respectively. Conclusions: Peruvian NSCLC patients represent a population with a high frequency of pathogenic and targetable mutations, being EGFR mutations and ALK rearrangements the most prevalent ones. Despite limited access, a great proportion of patients received target therapy, achieving remarkable survival.

First-degree family history of cancer can be a potential risk factor among head and neck cancer patients in an isolated Mizo tribal population, northeast India

BackgroundHead and Neck Squamous Cell Carcinoma (HNSCC) is commonly associated with tobacco and alcohol consumption. The aim of this study is to find the association between the risk factors with HNSCC in a small tribal population of Mizoram, North-East India. MethodsData were obtained through consented questionnaires and Logistic Regression was used to calculate the Odds Ratio (OR) between the parameters and HNSCC. ResultSignificant association was observed for smoking and alcohol with an OR of 6.703 and 4.527, respectively. The OR was found to increase with increase in smoking and alcohol consumption. Majority of the patients consumed local made alcohol and smoked the local made cigarettes known as Zozial. Moreover, the First-Degree Family History of Cancer showed a significant OR of 1.921 (95% CI: 1.040–3.547). ConclusionRegardless of the duration of smoking or alcohol consumption, Family History of Cancer might influence the risk of HNSCC. Further screening is essential to evaluate the potential role of germline mutational effect on development of HNSCC in the population.

Functional polymorphisms of the lncRNA H19 promoter region contribute to the cancer risk and clinical outcomes in advanced colorectal cancer

BackgroundThe long non-coding RNA H19 plays critical roles in cancer occurrence, development, and progression. The present study is for the first time to evaluate the association of genetic variations in the H19 promoter region with advanced colorectal cancer (CRC) susceptibility, environmental factors, and clinical outcomes.Methods16 single-nucleotide polymorphisms (SNPs) were identified in the H19 gene promoter by DNA sequencing, and 3 SNPs among which including rs4930101, rs11042170, and rs2735970 further expanded samples with 572 advanced CRC patients and 555 healthy controls.ResultsWe found that harboring SNP [rs4930101 (P = 0.009), rs2735970 (P = 0.003), and rs11042170 (P = 0.003)] or carrying more than one combined risk genotypes significantly increased the risk for CRC [P < 0.0001, adjusted OR (95% CI) 6.48 (2.97–14.15)]. In the correlation analysis with environmental factors, rs2735970 and gender, combined risk genotypes (> 1 vs. ≤ 1) and family history of cancer demonstrated significant interactions. Furthermore, a remarkably worse clinical outcome was found in combined risk genotypes (> 1 vs. ≤ 1), especially in CRC patients with body weight ≥ 61 kg, smoking, and first-degree family history of cancer (Log-rank test: P = 0.006, P = 0.018, and P = 0.013, respectively). More importantly, the multivariate Cox regression analyses further verified that combined risk genotypes > 1 showed a prognostic risk factor for CRC patients with body weight ≥ 61 kg (P = 0.002), smoking (P = 0.008), and family history of cancer (P = 0.006). In addition, MDR analysis consistently revealed that the combination of selected SNPs and nine known risk factors showed a better prediction prognosis and represented the best model to predict advanced CRC prognosis.Conclusion3 SNPs of rs4930101, rs11042170, and rs27359703 among 16 identified SNPs of H19 gene remarkably increased CRC risk. Furthermore, the combined risk genotypes had a significant impact on environmental factors and clinical outcomes in the advanced CRC patients with body weight ≥ 61 kg, ever-smoking, and first-degree family history of cancer. These data suggest that H19 promoter SNPs, especially these combined SNPs might be more potentially functional biomarkers in the prediction of advanced CRC risk and prognosis.

Prognostic impact of family history of cancer in Southern Chinese patients with esophageal squamous cell cancer.

Background: First degree family history of cancer is associated with developing esophageal cancer and sparse data is about the impact on poor survival among established esophageal squamous cell cancer (ESCC) patients. In this study, we investigated the prognoses of patients with ESCC with a family history.Methods: A total of 479 ESCC patients were retrospectively enrolled from a Southern Chinese institution. A positive family history was defined as having malignant cancer among parents and siblings. Kaplan-Meier plots and Cox proportional hazards regressions were applied for overall survival (OS) and progression-free survival (PFS).Results: Among 479 patients, 119 (24.8%) and 68 (14.2%) reported a first-degree family history of cancer and digestive tract cancer, respectively. Compared with patients without a family history of cancer, the adjusted hazard ratios (HR) among those with it were 1.40 (95% CI, 1.08-1.82, p=0.011) for death, 1.36 (95% CI, 1.05-1.76, p=0.018) for progression. Similar results were observed in those with a family history of digestive tract cancer (HR=1.69, 95%CI, 1.24-1.98, p=0.001 for death and HR=1.77, 95%CI, 1.30-2.37, p<0.001 for progression, respectively). Furthermore, there was a trend for increasing risk of overall mortality (p=0.021, p=0.004, respectively), and progression (p=0.022, p=0.001, respectively) with an increasing number of affected family members.Conclusion: A first-degree family history of cancer, especially digestive tract cancer is associated with poor survival for established ESCC patients and plays an important role in prognosis. The patients with a family history of cancer might need a greater intensity of treatment and more frequent follow-up.

Polymorphisms in DNA repair pathway genes and ABCG2 gene in advanced colorectal cancer: correlation with tumor characteristics and clinical outcome in oxaliplatin-based chemotherapy.

ObjectiveMultiple factors are involved in oxaliplatin-resistant process in colorectal cancer (CRC) patients including decreased drug accumulation and enhanced capacity to repair and tolerate DNA damage. In the present study, we aimed to assess the impact of six single-nucleotide polymorphisms (SNPs) in DNA repair genes and ABCG2 gene on prognosis in advanced CRC patients treated with oxaliplatin-based chemotherapy.MethodsIn this study, 580 advanced CRC patients were recruited. Six SNPs of DNA repair genes (XPA rs10817938, XPA rs2808668, XPC rs2607775, and WRN rs1346044) and ABCG2 gene (rs2231142 and rs2622621) were genotyped by using the TaqMan assay.ResultsRegarding interaction with environmental factors, ABCG2 rs2231142 and the first-degree family history of cancer and XPC rs2607775 or ABCG2 rs2622621 and lymph node metastases status demonstrated significant interactions. Of these six SNPs, XPA rs10817938 CT/ TT genotypes retained its significant association with longer overall survival (OS) (P=0.008) in CRC patients receiving oxaliplatin-based chemotherapy (n=580). Furthermore, a significantly better impact on the disease-free survival (DFS) (P=0.001) and OS (P<0.0001) was found in ABCG2 rs2231142CA/AA carriers. Furthermore, ABCG2 rs2622621 CG/GG genotype was verified to be an independent poor prognostic factor in DFS (P=0.010) and OS (P=0.030). In the stratification analysis, XPA rs10817938 CT/CC, rs2231142 CA/AA, and rs2622621 CC genotypes of ABCG2 were predictive of significantly better prognosis in the patients with tumor differentiation grade 3 (n=523), clinical stage IV (n=73), or lymph node-positive status (n=557). Additionally, multivariate logistic regression and multiple dimension reduction analysis consistently revealed that the combination of selected SNPs and five known risk factors showed a better prediction prognosis and represented the best model to predict CRC prognosis.ConclusionThe current data indicated that the XPA gene and ABCG2 gene had significant interaction with environmental factors and prognosis, which could provide a comprehensive understanding of the implications of those SNPs in the prediction of prognosis in advanced CRC patients receiving oxaliplatin-based chemotherapy.

Family history of cancer and the risk of childhood solid tumours: a Norwegian nationwide register-based cohort study

Background:It is not clear if family history of cancer increases risk of cancer in children.Methods:We followed-up a total of 2 610 937 children born between 1960 and 2001 for cancer risk, and their parents and siblings. In this period, 2477 primary childhood solid tumours (except lymphoma) were diagnosed. The data from the Norwegian Family and Life Course Study and from the Norwegian Cancer Register were used. Classification of hereditary cancer syndromes was based on tumour histology, pedigrees and Chompret’s criteria.Results:An association between risk of childhood tumours and first-degree family history of early onset of solid tumours was observed for central nervous system tumours (2.3-fold), neuroblastoma (2.3-fold), retinoblastoma (6.1-fold), hepatic tumours (4.0-fold), and melanomas (8.3-fold). Elevated risk was also seen for osteosarcomas (1.5-fold) when considering first-degree family history of cancer diagnosed at any age. The risk of hepatic tumours, neuroblastomas and melanomas remained elevated even after controlling for probable hereditary cancer syndromes.Conclusions:The increased risk for several childhood solid site cancers among those with first-degree relatives diagnosed with solid cancer suggests that genetic or environmental factors are involved. The fact that these associations remained after controlling for hereditary cancer syndromes indicates other genetic mechanisms might be involved.

Accuracy of self-reported family history of cancer, mutation status and tumor characteristics in patients with early onset breast cancer

Background: The main objectives of this study were to evaluate the concordance between self-reported and registry-reported information regarding family history of breast cancer (BC), ovarian cancer (OvC) and other types of cancer in first-degree relatives of patients with early onset BC, and to determine the frequency of mutation carriers and non-mutation carriers. The secondary objective was to describe tumor characteristics for each mutation group.Material and methods: Between 1993 and 2013, 231 women who were ≤35 years old when diagnosed with BC were registered at the Oncogenetic Clinic at Skåne University Hospital in Lund, Sweden. Self-reported and registry-reported information regarding first-degree family history of cancer was collected together with information regarding tumor characteristics.Results: Almost perfect agreement was observed between self-reported and registry-reported information regarding first-degree family history of BC (κ = 0.92) and OvC (κ = 0.86). Lesser agreement was observed between reports regarding family history of other types of cancer (κ = 0.51). Mutation screening revealed pathogenic germline mutations in 30.4%; 18.8% in BRCA1, 7.1% in BRCA2 and 4.5% in other genes. Compared with other mutation groups, BRCA1 mutation carriers were more likely to be diagnosed with high-grade, ER-, PR- and triple-negative tumors.Conclusions: Our results demonstrate that physicians and genetic counselors can rely on self-reported information regarding BC and OvC in first-degree relatives. However, self-reported information regarding other types of cancer is not communicated as effectively, and there should be more focus on retrieving the correct information regarding family history of all tumor types. Furthermore, we observed that even though all BC patients fulfilled the criteria for genetic counseling and testing, a large number of patients diagnosed at ≤35 years of age did not receive genetic counseling at the Oncogenetic Clinic. This finding merits further elucidation.

Risk and protective factors for the occurrence of sporadic pancreatic endocrine neoplasms.

Pancreatic neuroendocrine neoplasms (PNENs) represent 10% of all pancreatic tumors by prevalence. Their incidence has reportedly increased over recent decades in parallel with that of pancreatic adenocarcinoma. PNENs are relatively rare, and of the few institutions that have published potential risk factors, findings have been heterogeneous. Our objective was to investigate the association between potential risk and protective factors for the occurrence of sporadic PNENs across a European population from several institutions. A multinational European case-control study was conducted to examine the association of selected environmental, family and medical exposure factors using a standardized questionnaire in face-to-face interviews. A ratio of 1:3 cases to controls were sex and age matched at each study site. Adjusted univariate and multivariate logistic regression analysis were performed for statistically significant factors. The following results were obtained: In 201 cases and 603 controls, non-recent onset diabetes (OR 2.09, CI 1.27-3.46) was associated with an increased occurrence of PNENs. The prevalence of non-recent onset diabetes was higher both in cases with metastatic disease (TNM stage III-IV) or advanced grade (G3) at the time of diagnosis. The use of metformin in combination with insulin was also associated with a more aggressive phenotype. Drinking coffee was more frequent in cases with localized disease at diagnosis. Our study concluded that non-recent onset diabetes was associated with an increased occurrence of PNENs and the combination of metformin and insulin was consistent with a more aggressive PNEN phenotype. In contrast to previous studies, smoking, alcohol and first-degree family history of cancer were not associated with PNEN occurrence.

Diabetes, Smoking, Alcohol Use, and Family History of Cancer as Risk Factors for Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis

Background and Aims: Risk factors for pancreatic neuroendocrine tumors (PNETs) are not well understood. The aim of this systematic review was to assess if diabetes mellitus, smoking, alcohol use, and family history of cancer are risk factors for PNETs. Methods: MEDLINE and abstracts from the European and North American Neuroendocrine Tumor Societies (ENETS and NANETS) were searched for studies published until October 2013. Eligible studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Five studies evaluating 4 individual populations were included (study accrual period 2000-2011) into the meta-analysis, involving 827 cases (range 160-309 per study) and 2,407 controls (range 233-924 per study). All studies had a case-control design and described regional series. The pooled adjusted odds ratio was 2.74 (95% CI: 1.63-4.62; p < 0.01; I² = 60.4%) for history of diabetes, 1.21 (95% CI: 0.92-1.58; p = 0.18; I² = 45.8%) for ever smoking, 1.37 (95% CI: 0.99-1.91; p = 0.06; I² = 0.0%) for heavy smoking, 1.09 (95% CI: 0.64-1.85; p = 0.75; I² = 85.2%) for ever alcohol use, 2.72 (95% CI: 1.25-5.91; p = 0.01; I² = 57.8%) for heavy alcohol use, and 2.16 (95% CI: 1.64-2.85; p < 0.01; I² = 0.0%) for first-degree family history of cancer. Conclusions: Diabetes mellitus and first-degree family history of cancer are associated with an increased risk of sporadic PNET. There was also a trend for diagnosis of sporadic PNET associated with heavy smoking. Alcohol use may be a risk factor for PNET, but there was considerable heterogeneity in the meta-analysis. These results suggest the need for a larger, homogeneous, international study for the clarification of risk factors for the occurrence of PNET.

The association between having a first-degree family history of cancer and smoking status

ObjectiveA diagnosis of cancer within the family provides an opportunity for smokers to adopt a health-promoting behavior. This study examines the associations between having a first-degree family history of cancer and smoking status using population-based data with a large and diverse sample. MethodCross-sectional data from the 2009 California Health Interview Survey on 47,331 adults were analyzed. Sample weights were applied to account for the survey design with results generalizable to non-institutionalized adults in California (27.4million). ResultsIn 2009, 3.7million (13.6%) adults were current-smokers, 6.3million (23.0%) were former smokers and 17.4million (63.4%) were never-smokers. Nine-million-six-hundred-thousand (35%) had a first-degree family history of cancer. Controlling for all covariates, first-degree family history of cancer was significantly associated with being a current smoker (OR=1.16; 95% CI=1.01–1.35) and to being a former smoker (OR=1.17; 95% CI=1.05–1.30). ConclusionIn California, although many adults with a first-degree family history of cancer quit smoking, a significant subset still smoke which places them at higher risk for poor health outcomes. This subset represents an important target population for smoking cessation interventions.

Family history and survival of patients with gastric cancer: a meta-analysis.

Previous studies have generated conflicting evidence regarding associations between family history and survival after gastric cancer surgery. In this study, we investigated this question using a meta-analysis. To identify relevant studies, PubMed and Embase databases were searched up to June 2013. Two reviewers independently assessed search results and data extraction of included studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) were calculated based on fixed- or random- effects models. Homogeneity of effects across studies was assessed using x2 test statistics and quantified by I2. A total of five studies were selected according to the inclusion criteria. The total number of patients included was 2,030, which ranged from 145 to 598 per study. There was no significant difference in OS by family history of cancer (HR=0.83, 95%CIs=0.50-1.38), but subgroup analysis of patients with a first-degree family history of cancer (HR=0.74, 95%CIs=0.60-0.93) and gastric cancer family history (HR=0.56, 95%CIs=0.41-0.76) tended to show better OS in these patients. This meta-analysis suggests that a first-degree family history of cancer or gastric cancer family history is associated with better survival of gastric cancer patients after surgery, after a systematic review of five previous studies. These results can be applied by clinicians when counselling patients regarding their risk of death from gastric cancer. Further study is needed to investigate the underlying mechanism between family history and survival in gastric cancer patients.

Abstract B60: Contraceptive methods and ovarian cancer risk among Chinese women: A report from the Shanghai Women Health Study

Abstract Background: Oral contraceptive (OC) use is known to be associated with reduced ovarian cancer risk; associations with other contraceptive methods, such as intrauterine devices (IUD) and tubal ligation (TL), are less clear. The majority of studies conducted to date have used case-control designs; fewer cohort studies have been conducted, especially among Asian women. As contraception use is popular among Chinese women, and the use of different contraceptive methods differs from Western countries, differences in associations with ovarian cancer risk may exist. Methods: Data from the prospective Shanghai Women's Health Study (SWHS) was used to evaluate associations between different contraceptive methods and risk of ovarian cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression; models included adjustment for age, education, years of ovulation, body mass index (BMI), first-degree family history of cancer (yes/no), and regular physical activity within 5 years (yes/no). Results: A total of 164 ovarian cancer cases occurred among 70,349 women after an average follow-up time of 11.74 years. The majority of women had ever used any contraception (77.0%), including OC use (20.4%), contraceptive shots (2.6%), IUD use (55.6%) and TL (14.7%). Ever use of any contraception method was associated with a non-significant reduction in ovarian cancer risk (HR: 0.83, 95% CI: 0.58-1.19). Similarly, among users of contraception, women with durations of OC use longer than the median (≥2 years) tended to have lower ovarian cancer risk (HR: 0.60, 95% CI: 0.26-1.39), while women with durations of IUD use longer than the median (≥23 years) had significantly decreased ovarian cancer risk (HR: 0.48, 95% CI: 0.30-0.75). Conclusion: Longer durations of IUD use had beneficial effects on ovarian cancer risk among Chinese women. Due to the high prevalence and long duration of IUD use among Chinese women, and the protective association seen in this study, we estimate that approximately 20 ovarian cancer cases (12.0%) were prevented in this study population. Therefore, patterns of use of different contraceptive methods in China may contribute to the lower incidence of ovarian cancer observed in this country. Citation Format: Zhezhou Huang, Alicia Beeghly-Fadiel, Honglan Li, Wanqing Wen, Yutang Gao, Wei Zheng, Xiao-Ou Shu. Contraceptive methods and ovarian cancer risk among Chinese women: A report from the Shanghai Women Health Study. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B60.

Significance of MDM2 and P14ARF polymorphisms in susceptibility to differentiated thyroid carcinoma

Murine double minute 2 (MDM2) oncoprotein and p14(ARF) tumor suppressor play pivotal roles in regulating p53 and function in the MAPK pathway, which is mutated frequently in differentiated thyroid carcinoma (DTC). We hypothesized that functional polymorphisms in the promoters of MDM2 and p14(ARF) contribute to the interindividual difference in predisposition to DTC. MDM2-rs2279744, MDM2-rs937283, p14(ARF)-rs3731217, and p14(ARF)-rs3088440 were genotyped in 303 patients with DTC and 511 cancer-free healthy controls. Multivariate logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). MDM2-rs2279744 and p14(ARF)-rs3731217 were associated with a significantly increased risk of DTC (MDM2-rs2279744: TT versus TG/GG; OR, 1.5; 95% CI, 1.1-2.0; p14(ARF)-rs3731217: TG/GG versus TT; OR, 1.7; 95% CI, 1.2-2.3). No association was found for MDM2-rs937283 or p14(ARF)-rs3088440. Individuals carrying 3-4 risk genotypes of MDM2 and p14(ARF) had 2.2 times (95% CI, 1.4-3.5) the risk for DTC of individuals carrying 0-1 risk genotypes (P trend = .021). The combined effect of MDM2 and p14(ARF) on risk of DTC was confined to young subjects (≤ 45 years), nonsmokers, nondrinkers, and subjects with a first-degree family history of cancer. These associations were quite similar in strength when cases were restricted to those with papillary thyroid cancer. Our results suggest that polymorphisms of MDM2 and p14(ARF) contribute to the interindividual difference in susceptibility to DTC, either alone or more likely jointly. The observed associations warrant further confirmation in independent studies.

Functional polymorphisms in the insulin‐like binding protein‐3 gene may modulate susceptibility to differentiated thyroid carcinoma in Caucasian Americans

The insulin-like growth factor (IGF) pathway is believed to play a pivotal role in thyroid carcinogenesis. Polymorphisms of IGF-1 and IGF binding protein-3 (IGFBP-3) have been associated with modulation of risk for the emergence of assorted common malignancies, but studies of the influence of such polymorphisms on risk of differentiated thyroid carcinoma (DTC) are lacking. In a case-control study of 173 DTC patients, 101 patients with benign thyroid disease, and 401 controls, an unconditional logistical regression model adjusted for age and sex was applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between polymorphisms of IGF-1 and IGFBP-3 and DTC risk. IGFBP-3 rs2132572 GA/AA genotypes were associated with a decreased risk of DTC (adjusted OR = 0.6, 95% CI: 0.4-0.9), particularly multifocal DTC (adjusted OR = 0.3, 95% CI: 0.1-0.7). The association with DTC was more evident in subjects with a first-degree family history of cancer (adjusted OR = 0.4, 95% CI: 0.2-0.7, P(interaction) = 0.013) and non-drinkers (adjusted OR = 0.4, 95% CI: 0.2-0.7, P(interaction) = 0.028). A four single nucleotide polymorphism haplotype of IGFBP-3 was associated with a decreased risk of DTC (adjusted OR = 0.7, 95% CI: 0.5-1.0, P = 0.030). Our study suggests that polymorphic IGFBP-3 may be involved in susceptibility to DTC.

No Association between Matrix Metalloproteinase (MMP)-1, MMP-3, and MMP-7 SNPs and Endometrial Cancer Risk

The matrix metalloproteinases (MMP) function as regulators of the dynamic tissue remodeling that occurs in the endometrial lining of the uterus during the normal human menstrual cycle; dysregulation of the MMPs is thought to contribute to the development of both endometriosis and endometrial cancer

Consistency of self-reported first-degree family history of cancer in a population-based study

The aim of this study was to assess the prevalence and consistency of self-reported family history of cancer among first-degree relatives (FDR) in a population-based study. Women at primary care units (PCU) were submitted to a questionnaire about cancer family history. Consistency of the report was determined by comparing self-reported history at the PCU to data from subsequent genetic evaluations and/or cancer confirmatory documents. Consistency in relation to degree of education, reported tumor type and reported age at cancer diagnosis in FDR was assessed. In 8,881 women interviewed, the prevalence of cancer in an FDR was 25.14% (CI 95%: 24.14; 25.94). Mean age was 40.29 years and most (70.26%) had < or = 8 years of education. There was a good agreement of self-reported cancer history at the PCU and in subsequent genetic evaluations [Kappa coefficient = 0.76 (P < 0.05)]. Inconsistencies were not related to low literacy (chi (2) = 2.027; P = 0.363). Consistency of the reported information for cancer status, cancer type and age of onset was 92.59%, 85.33% and 92.64%, respectively. The prevalence of cancer history in an FDR was similar to previous reports in other populations. Consistency and reliability of the self-reported information was high, regardless of educational level.

Frequency and accuracy of the first-degree family history of cancer in a community-based sample of women with low literacy in the South of Brazil

1549 A positive family history (FH) in first-degree relatives (FDR) is one of the most important risk factors for breast cancer. However, there are few published studies about its prevalence in community-based samples. The aim of this study was to evaluate the prevalence of first-degree cancer FH in an unselected sample of low-literacy women recruited in primary-care health centers through an interview and questionnaire. Accuracy of self- reported cancer history in a FDR was also evaluated. Of 6514 women, 4.5% were illiterate and 66% had elementary education. When asked about cancer FH, 23.3% had at least one FDR with cancer. The accuracy of reported FDR history was evaluated by telephone 12 months after the initial interview. Of the 1516 women reporting at least one FDR with cancer, a random telephone contact was made with 710 (46%). In 88% of the patients, the history reported by phone was exactly the same as the one reported initially. In addition, 29 of 710 patients contacted by phone denied cancer history in FDR. In 7.9% of the patients, FDR history of cancer was confirmed, but one of the following inconsistencies in relation to the original report was described: the type of cancer was different or the relative affected was different. We conclude that a significant proportion of women report history of cancer in a FDR accurately, despite of low literacy. These findings have considerable relevance to clinical practice and are important to validate FH taking in cancer risk estimation models that use this variable. No significant financial relationships to disclose.

Is Family History of Breast Cancer Associated with Therapy-Related Myelodysplastic Syndrome and Therapy-Related Leukemia?.

Therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML) occur in a subset of patients treated with chemotherapy and/or radiation for various primary malignancies. Whether or not a patient develops t-MDS/t-AML can be influenced by a combination of genetic and environmental factors. We conducted a retrospective analysis of t-MDS/t-AML patients who had cytogenetic analyses performed at the University of Chicago Hospitals between 1972 and 2001 to determine if a family history of cancer could be associated with t-MDS/t-AML development. These included 141 males and 165 females whose median age was 51 years (range was from 3–83 years) at the time of primary diagnosis and 58 years (range was from 6–86 years) at the time of t-MDS/t-AML presentation. Out of 306 patients, data on first-degree family history of cancer was documented in 160 patients, but there was no statistically significant difference in the characteristics examined below between patients with self-reported family history of cancer and patients with undocumented family histories. A first-degree family history of any cancer was reported in 89 patients (55.6%). The prevalence of family history of specific sites were: 25 (15.6%) of breast cancer, 23 (14.4%) of lung cancer, 13 (8.1%) of colorectal cancer, 11 (6.9%) of hematologic malignancy, 10 (2.3%) of prostate cancer, 6 (3.8%) of stomach cancer, 5 (3.1%) of uterine cancer, 5 (3.1%) of CNS cancer, 5 (3.1%) of pancreas cancer, 4 (2.5%) of melanoma, 3 (1.9%) of oral-pharyngeal cancer, 3 (1.9%) of ovarian cancer, 3 (1.9%) of cervical cancer, 2 (1.3%) of vulvar cancer, 1 (0.6%) each of bladder cancer, sarcoma, renal cancer, or esophageal cancer. Of note, only a family history of breast cancer was associated with clinical presentation as show in Table 1 below. Patients with a family history of breast cancer were also more likely to have a chromosome 5 and/or 7 abnormality (84%) than patients without (62%, p=0.04). There was no significant association between family history of cancer at other sites and clonal cytogenetic abnormalities. A subgroup analysis was conducted in patients with a primary diagnosis of breast or ovarian cancer. Of the 24 patients who had data on family history of cancer, 16.7% reported having a first degree relative with breast cancer. These findings suggest a possible genetic component linking family history of breast cancer and development of t-MDS/t-AML, as was previously reported by Rauscher et al. (2002) for de novo adult leukemia incidence. Further studies of family histories of cancer, in particular breast cancer among patients receiving chemotherapy and/or radiation, could potentially elucidate the genetic basis of leukemia and ultimately lead to new tools for risk assessment, early detection or prevention of secondary leukemia in cancer survivors. [Display omitted]