Family history of cancer predicts endometrial cancer risk independently of Lynch Syndrome: Implications for genetic counselling.

OBJECTIVE: To determine endometrial cancer (EC) risk according to family cancer history, including assessment by degree of relatedness, type of and age at cancer diagnosis of relatives. METHODS: Self-reported family cancer history was available for 1353 EC patients and 628 controls. Logistic regression was used to quantify the association between EC and cancer diagnosis in ≥1 first or second degree relative, and to assess whether level of risk differed by degree of relationship and/or relative's age at diagnosis. Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression. RESULTS: Report of EC in ≥1 first- or second-degree relative was associated with significantly increased risk of EC (P=3.8×10-7), independent of lifestyle risk factors. There was a trend in increasing EC risk with closer relatedness and younger age at EC diagnosis in relatives (PTrend=4.43×10-6), and with increasing numbers of Lynch cancers in relatives (PTrend≤0.0001). EC risk associated with family history did not differ by proband tumor MMR status, or histological subtype. Reported EC in first- or second-degree relatives remained associated with EC risk after conservative correction for potential misreported family history (OR 2.0; 95% CI, 1.24-3.37, P=0.004). CONCLUSION: The strongest predictor of EC risk was closer relatedness and younger EC diagnosis age in ≥1 relative. Associations remained significant irrespective of proband MMR status, and after excluding MMR pathogenic variant carriers, indicating that Lynch syndrome genes do not fully explain familial EC risk.

Women with family cancer history are at risk for poorer physical quality of life and lower self-efficacy: a longitudinal study among men and women with non-small cell lung cancer.

BACKGROUND: We investigated the determinants of trajectories of physical symptoms related to lung cancer (a quality of life [QOL] aspect) and self-efficacy among patients with non-small cell lung cancer (NSCLC). It was hypothesized that gender and family cancer history in first-degree relatives would have synergistic effects on QOL-lung cancer specific symptoms and self-efficacy. Women with family cancer history were expected to be at risk of poorer adjustment. METHODS: Quantitative, longitudinal design was applied. Participants provided their responses at 3-4 days after surgery, 1-month follow-up, and 4-month follow-up. We recruited 102 in-patients (men: 51%) with NSCLC who underwent surgery aimed at removing a lung tumor. Self-report data were collected with QLQ-LC13 and a scale for self-efficacy for managing illness. RESULTS: Mixed-models analysis indicated that trajectories of physical quality of life (symptoms of lung cancer) as well as self-efficacy were unfavorable among women with family cancer history. CONCLUSIONS: Among NSCLC patients, gender and family cancer history may be considered basic screening criteria for identifying groups of patients at risk for poorer physical QOL (higher level of physical symptoms related to lung cancer) and lower incline of self-efficacy after cancer surgery.

A novel environmental exposure index and its interaction with familial susceptibility on oral cancer in non-smokers and non-drinkers: a case-control study.

The objective of this study was to explore the collective effect of environmental factors and its interaction with familial susceptibility on oral cancer among non-smokers and non-drinkers (NSND). A hospital-based case-control study, including 319 oral cancer patients and 994 frequency-matched controls, was conducted in Fujian, China. We raised a weighed environmental exposure index according to nine significant environmental factors obtained from multivariable logistic regression model. And then, the index was classified into three categories according to the tertiles of controls (<1.34, 1.34-2.43, and >2.43). Multiplicative and additive interactions were evaluated between environmental exposure index and family cancer history. Our results showed that environmental exposure index was associated with an increased risk of oral cancer especially for those with family cancer history. Compared to subjects with low environmental exposure index and without family cancer history, those with high index and family cancer history showed the highest magnitude of OR in oral cancer risk (OR 10.40, 95% CI 5.46-19.80). Moreover, there was a multiplicative interaction between environmental exposure index and family cancer history for the risk of oral cancer (P < 0.001). This study puts forward a novel environmental exposure index, which enables a comprehensive evaluation on the overall effect of environmental risk factors on oral cancer among NSND and may interact with family cancer history. Further studies are warranted to explore the underlying mechanisms.

Family history of cancer and risk of pediatric and adolescent Hodgkin lymphoma: A Children's Oncology Group study.

Family history of lymphoid neoplasm (LN) is a strong and consistently observed Hodgkin lymphoma (HL) risk factor, although it has been only marginally examined in pediatric/adolescent patients. Here, healthy control children identified by random digit dialing were matched on sex, race/ethnicity and age to HL cases diagnosed at 0-14 years at Children's Oncology Group institutions in 1989-2003. Detailed histories were captured by structured telephone interviews with parents of 517 cases and 783 controls. Epstein-Barr virus (EBV) RNA detection was performed for 355 available case tumors. Two analytic strategies were applied to estimate associations between family cancer history and pediatric/adolescent HL. In a standard case-control approach, multivariate conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (CIs). In a reconstructed cohort approach, each relative was included as a separate observation, and multivariate proportional hazards regression was used to produce hazard ratios (HRs) and 95% CIs. Using the latter, pediatric/adolescent HL was associated with a positive family history (HR = 1.20, 95% CI: 1.06-1.36), particularly early-onset cancers (HR = 1.30, 95% CI: 1.06-1.59) and those in the paternal lineage (HR = 1.38, 95% CI: 1.16-1.65), with a suggested association for LN in first-degree relatives (HR = 3.61, 95% CI: 0.87-15.01). There were no discernable patterns for EBV+ versus EBV- HL. The clustering of LN within pedigrees may signal shared genetic susceptibility or common environmental exposures. Heritable genetic risk variants have only recently begun to be discovered, however. These results are consistent with other studies and provide a compelling rationale for family-based studies to garner information about genetic susceptibility to HL.

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

OBJECTIVE: A 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. METHOD: Cross-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 (27.4 million). RESULTS: In 2009, 3.7 million (13.6%) adults were current-smokers, 6.3 million (23.0%) were former smokers and 17.4 million (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). CONCLUSION: In 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.

Barriers and facilitators to the implementation of family cancer history collection tools in oncology clinical practices.

INTRODUCTION: This study aimed to identify barriers and facilitators to the implementation of family cancer history (FCH) collection tools in clinical practices and community settings by assessing clinicians' perceptions of implementing a chatbot interface to collect FCH information and provide personalized results to patients and providers. OBJECTIVES: By identifying design and implementation features that facilitate tool adoption and integration into clinical workflows, this study can inform future FCH tool development and adoption in healthcare settings. MATERIALS AND METHODS: Quantitative data were collected using survey to evaluate the implementation outcomes of acceptability, adoption, appropriateness, feasibility, and sustainability of the chatbot tool for collecting FCH. Semistructured interviews were conducted to gather qualitative data on respondents' experiences using the tool and recommendations for enhancements. RESULTS: We completed data collection with 19 providers (n = 9, 47%), clinical staff (n = 5, 26%), administrators (n = 4, 21%), and other staff (n = 1, 5%) affiliated with the NCI Community Oncology Research Program. FCH was systematically collected using a wide range of tools at sites, with information being inserted into the patient's medical record. Participants found the chatbot tool to be highly acceptable, with the tool aligning with existing workflows, and were open to adopting the tool into their practice. DISCUSSION AND CONCLUSIONS: We further the evidence base about the appropriateness of scripted chatbots to support FCH collection. Although the tool had strong support, the varying clinical workflows across clinic sites necessitate that future FCH tool development accommodates customizable implementation strategies. Implementation support is necessary to overcome technical and logistical barriers to enhance the uptake of FCH tools in clinical practices and community settings.

Internet-based eHealth technology for emotional well-being among the older adults with a family cancer history: full mediation effects of health information self-efficacy and cancer fatalism.

BACKGROUND: Older adults with a family cancer history (FCH) face an increased cancer risk, which may adversely impact their emotional well-being. Internet-based eHealth technologies (IETs) provide a potential solution to this challenge. This study examines the influence of using IETs on the emotional well-being of older adults with FCH. It also delves into the mediating pathways through health information self-efficacy and cancer fatalism. METHODS: This study conducted a mediation analysis using data from the Health Information National Trends Survey (HINTS 6) collected from March 2022 to November 2022, focusing on older adults with FCH who had previously searched for cancer-related information (N = 1,280). RESULTS: In the mediation model, no positive direct associations between IETs usage and emotional well-being were found. Only health information self-efficacy and cancer fatalism were found to mediate the relationship between IETs usage and emotional well-being serially (ß = 0.007, 95% CI [0.003, 0.012]). CONCLUSIONS: The findings inform health information professionals and healthcare practitioners on enhancing the impact of IETs usage on individual health information self-efficacy, which mitigates cancer fatalism, contributing to better emotional well-being in the digital era.

Characteristics of TP53 germline variants and their correlations with Li-Fraumeni syndrome or Li-Fraumeni-like syndrome in Chinese tumor patients.

Li-Fraumeni syndrome (LFS), a rare autosomal-dominant inheritance condition, is associated with a family cancer history as well as pathogenic/likely-pathogenic TP53 germline variants (P/LP TP53 GV). The current clinical methods for detecting LFS are limited. Here, we retrospectively investigate P/LP TP53 GV among Chinese cancer patients by next-generation sequencing and evaluate its relationship with a family cancer history. A total of 270 out of 19,226 cancer patients have TP53 GV, including 53 patients with P/LP TP53 GV. Patients with P/LP TP53 GV are mainly found in male with glioma, lung cancer or sarcoma. The median age of diagnosis for P/LP TP53 GV patients is significantly lower than that of non-P/LP TP53 GV patients (31-years vs. 53-years; P < 0.01). One LFS patient and 3 Li-Fraumeni-like syndrome (LFL) patients are among the 26 followed-up P/LP TP53 GV patients. Among 25 types of P/LP TP53 GV, the highest variant frequencies occurred at codon 175 and 248. p.M237I, p.R158H, p.C238Y and p.C275R, are firstly identified among the Chinese LFS/LFL patients. This study reports the (P/LP) TP53 GV characteristics of Chinese pan-cancer patients. These findings suggest analyzing the P/LP TP53 GV in cancer patients is an effective strategy for identifying cancer predisposition syndrome.

Prognostic Value of a Family History of Oral Tongue Squamous Cell Carcinoma: A Matched-Pair Study.

OBJECTIVES/HYPOTHESIS: To analyze the prognostic value of a family cancer history for predicting survival in patients with oral tongue squamous cell carcinoma (SCC). STUDY DESIGN: Retrospective case series. METHODS: Each patient with a family history was paired with one patient with sporadic oral tongue SCC without a family history. The primary endpoint was disease-specific survival (DSS). RESULTS: In total, 124 patients were enrolled as participants with a family cancer history, and the 5-year DSS rate was 51%. In the matched group, the 5-year DSS rate was 40%. The difference was significant (P = .032). In the smoking patients with a family history, the 5-year DSS rate was 43%. In the smoking patients from the matched group, the 5-year DSS rate was 17%; the difference was significant (P = .028). In nonsmoking patients with a history of cancer, the 5-year DSS rate was 51%; in nonsmoking patients in the matched group, the 5-year DSS rate was 40%; the difference was not significant (P = .141). CONCLUSIONS: A family cancer history is associated with improved DSS in surgically treated oral tongue SCC patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E605-E610, 2020.

Synergistic Effect Between Full-Term Pregnancy/Breastfeeding And Familial Susceptibility On Breast Cancer Risk.

BACKGROUND: Breast cancer is the most common cancer in women worldwide, and reproductive factors and family history of malignancy are considered as high risk factors. The present study aimed to evaluate the synergistic effect of reproductive factors and family history on breast cancer. METHOD: A total of 1215 breast cancer patients and 1215 control participants from two medical centers were enrolled, and reproductive factor history and family cancer history information was collected. Multivariate logistic regression analyses were performed to estimate the adjusted odds ratio (OR), and synergy index (SI) was used to assess the combined effect of potential factors. RESULTS: Compared to the controls, a negative association between full-term pregnancy/breastfeeding and breast cancer was observed regardless of the status of family cancer history (OR: 0.675, 95% CI: 0.560-0.814 and OR: 0.631, 95% CI: 0.503-0.789 respectively) after adjustment of other confounders, while the risk effect of abortion was unproven. The synergistic effect of history of full-term pregnancy and family history of malignancy was indicated in the combined analyses with SI as 9.429 (95% CI:1.248-71.245). CONCLUSION: Full-term pregnancy/breastfeeding were protective factors against breast cancer and synergistic additive effect was demonstrated between no full-term pregnancy/breastfeeding and a family history of malignancy on the risk of breast cancer.

Association Between Health Behaviors and Family History of Cancer in Cancer Survivors: Data From the Korean Genome and Epidemiology Study.

BACKGROUND: We compared health behaviors, including current smoking, alcohol drinking, regular exercise, obesity, and abdominal obesity, among Korean cancer survivors with and without family history of cancer. METHODS: This study included 5,247 cancer survivors with family history of cancer (1,894 with and 3,353 without), who were recruited from the Health Examinee cohort. Health behaviors were identified using questionnaire. Adjusted ORs (aORs) between health behaviors and family history of cancer were estimated by multivariate logistic regression analysis adjusted for sociodemographic factors. All analyses were conducted separately according to sex. RESULTS: Prevalence of current smoking, alcohol drinking, no regular exercise, obesity, and abdominal obesity was 16.3%, 48.3%, 36.0%, 31.3%, and 42.3% in male cancer survivors and 1.7%, 20.6%, 43.8%, 28.5%, and 72.5% in female, respectively. Health behaviors in male cancer survivors with and without family history of cancer were not significantly different after being adjusted for other covariates (aOR = 1.04, 95% CI = 0.75-1.44 for current smoking; aOR = 0.96, 95% CI = 0.76-1.22 for current drinking; aOR = 0.85, 95% CI = 0.66-1.10 for regular exercise; aOR = 0.96, 95% CI = 0.73-1.25 for obesity; aOR = 0.97, 95% CI = 0.75-1.25 for abdominal obesity). In female cancer survivors, there were no significant differences in health behaviors according to family history of cancer (aOR = 0.76, 95% CI = 0.44-1.32; aOR = 1.11, 95% CI = 0.94-1.31; aOR = 0.99, 95% CI = 0.87-1.14; aOR = 0.99, 95% CI = 0.85-1.16; aOR = 0.93, 95% CI = 0.80-1.10, respectively). CONCLUSIONS: We identified no significant differences in health behaviors according to family history of cancer in cancer survivors. More studies should be conducted to identify correlations between family history of cancer and prognosis in cancer survivors.

Association between family cancer history and risk of pancreatic cancer.

PURPOSE: Family history of pancreatic adenocarcinoma is an established risk factor for the disease. However, associations of pancreatic cancer with other familial cancers are less clear. We analyzed data from the Queensland Pancreatic Cancer Study (QPCS), an Australian population-based case-control study, to investigate associations between family history of various cancer types and risk of pancreatic cancer. MATERIALS AND METHODS: Our study included 591 pancreatic cancer patients and 646 controls, all of whom self-reported the histories of cancer in their first-degree relatives. We used logistic regression to estimate adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Based on our results, we conducted a systematic literature review using the Medline (OVID) database to identify articles pertaining to the association between family history of melanoma and risk of pancreatic cancer. A meta-analysis including associations in five published studies, unpublished results from a study co-author and the QPCS results was then performed using the DerSimonian and Laird random-effects model. RESULTS: Cases were more likely than controls to report a family history of pancreatic cancer (OR 2.20, 95% CI 1.16-4.19) and melanoma (OR 1.74, 95% CI 1.03-2.95), but not of breast, ovarian, respiratory, other gastrointestinal or prostate cancer. Meta-analysis of melanoma family history and pancreatic cancer risk yielded an OR of 1.22 (95% CI 1.00-1.51). CONCLUSIONS: Our results yield further evidence of increased risk of pancreatic cancer in those with family histories of the disease. We also provide suggestive evidence of an association between family history of melanoma and risk of pancreatic cancer.

High accuracy of family history of melanoma in Danish melanoma cases.

The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor but previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma probands who reported 199 cases of melanoma in relatives, of which 135 cases where in first degree relatives. We confirmed the diagnosis of melanoma in 77% of all relatives, and in 83% of first degree relatives. In 181 probands we validated the negative family history of melanoma in 748 first degree relatives and found only 1 case of melanoma which was not reported in a 3 case melanoma family. Melanoma patients in Denmark report family history of melanoma in first and second degree relatives with a high level of accuracy with a true positive predictive value between 77 and 87%. In 99% of probands reporting a negative family history of melanoma in first degree relatives this information is correct. In clinical practice we recommend that melanoma diagnosis in relatives should be verified if possible, but even unverified reported melanoma cases in relatives should be included in the indication of genetic testing and assessment of melanoma risk in the family.

Association Between Health Behaviors and Family History of Cancer in Cancer Survivors: Data From the Korean Genome and Epidemiology Study

BACKGROUND: We compared health behaviors, including current smoking, alcohol drinking, regular exercise, obesity, and abdominal obesity, among Korean cancer survivors with and without family history of cancer. METHODS: This study included 5,247 cancer survivors with family history of cancer (1,894 with and 3,353 without), who were recruited from the Health Examinee cohort. Health behaviors were identified using questionnaire. Adjusted ORs (aORs) between health behaviors and family history of cancer were estimated by multivariate logistic regression analysis adjusted for sociodemographic factors. All analyses were conducted separately according to sex. RESULTS: Prevalence of current smoking, alcohol drinking, no regular exercise, obesity, and abdominal obesity was 16.3%, 48.3%, 36.0%, 31.3%, and 42.3% in male cancer survivors and 1.7%, 20.6%, 43.8%, 28.5%, and 72.5% in female, respectively. Health behaviors in male cancer survivors with and without family history of cancer were not significantly different after being adjusted for other covariates (aOR = 1.04, 95% CI = 0.75–1.44 for current smoking; aOR = 0.96, 95% CI = 0.76–1.22 for current drinking; aOR = 0.85, 95% CI = 0.66–1.10 for regular exercise; aOR = 0.96, 95% CI = 0.73–1.25 for obesity; aOR = 0.97, 95% CI = 0.75–1.25 for abdominal obesity). In female cancer survivors, there were no significant differences in health behaviors according to family history of cancer (aOR = 0.76, 95% CI = 0.44–1.32; aOR = 1.11, 95% CI = 0.94–1.31; aOR = 0.99, 95% CI = 0.87–1.14; aOR = 0.99, 95% CI = 0.85–1.16; aOR = 0.93, 95% CI = 0.80–1.10, respectively). CONCLUSIONS: We identified no significant differences in health behaviors according to family history of cancer in cancer survivors. More studies should be conducted to identify correlations between family history of cancer and prognosis in cancer survivors.

Specifying exposure classification parameters for sensitivity analysis: family breast cancer history.

One of the challenges to implementing sensitivity analysis for exposure misclassification is the process of specifying the classification proportions (eg, sensitivity and specificity). The specification of these assignments is guided by three sources of information: estimates from validation studies, expert judgment, and numerical constraints given the data. The purpose of this teaching paper is to describe the process of using validation data and expert judgment to adjust a breast cancer odds ratio for misclassification of family breast cancer history. The parameterization of various point estimates and prior distributions for sensitivity and specificity were guided by external validation data and expert judgment. We used both nonprobabilistic and probabilistic sensitivity analyses to investigate the dependence of the odds ratio estimate on the classification error. With our assumptions, a wider range of odds ratios adjusted for family breast cancer history misclassification resulted than portrayed in the conventional frequentist confidence interval.