Behavioral risk factors among women presenting for genetic testing.

Considerable research attention has been given to the impact of genetic testing on psychological outcomes. Participation in genetic testing also may impact on health behaviors that increase the risk of cancer and other chronic diseases. The purpose of this study is to describe behavioral cancer risk factors of women who requested genetic testing for breast and ovarian cancer susceptibility (BRCA1, BRCA2). Before participation in a genetic testing program, 119 women completed a series of questionnaires designed to assess their health behaviors, perception of risk, and depressive symptomatology. Eight percent of participants were current smokers, 27% did not engage in at least moderate exercise, 46% did not regularly protect themselves from the sun, 39% did not consume at least five servings of fruits and vegetables per day, and 9% drank at least one alcoholic beverage per day. Poisson regression analysis revealed that age was the only predictor of behavioral risk profiles, with older women having fewer cancer risk behaviors. These patients who presented for genetic testing generally had better health behaviors than the general population. However, given their possible high-risk status, these patients should consider further improving their preventable cancer risk factors and, in particular, their diet, sun protection, and physical activity levels. Inclusion of behavioral risk factor counseling in the context of the genetic testing process may be an important opportunity to reach this at-risk population.     

Intention to pursue genetic testing for breast cancer among women due for screening mammography.

Because few studies have addressed the intention to pursue testing for breast cancer susceptibility among women in the general population, we examined whether women due for routine mammography would want such testing and what factors might impact on their decision to pursue testing. A questionnaire was mailed to women > or =50 years of age who had undergone a screening mammogram 12 to 14 months before the study. Univariate and multivariable analyses were conducted to identify factors associated with intention to pursue genetic testing. Approximately 41% of respondents probably or definitely intended to pursue testing. In univariate analysis, the intention to undergo testing was not significantly associated with age, education, marital status, potential effects on health or life insurance, or physician recommendation. Although significant in univariate analysis, family history of breast cancer and ethnicity were not significant in multivariable analysis. In both univariate and multivariable analysis, factors significantly associated with intention to undergo testing included awareness of genetic testing, cancer worry, and insurance coverage of testing cost. Intention also was associated with the respondent wanting to know whether she possessed the susceptibility gene, even if that knowledge would not impact on options for early detection or treatment. Given the relatively high level of interest in testing among women at average risk of breast cancer, these results may help health care professionals educate and counsel women regarding the appropriate use of genetic testing as well as breast cancer risk factors.     

Factors influencing risk‐based care of the childhood cancer survivor in the 21st century

The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient‐specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment‐related toxicity and possible targets for intervention in this population. Furthermore, although current long‐term follow‐up guidelines comprehensively address specific therapy‐related risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment‐related health risk and evolving treatment approaches, a patient‐centered and risk‐adapted approach to care that often requires a multidisciplinary team approach, including medical and behavioral providers, is necessary for this population. CA Cancer J Clin 2018;68:133‐152 . © 2018 American Cancer Society .     

Lung cancer risk in never-smokers: An overview of environmental and genetic factors

Lung cancer is the leading cause of cancer-related mortality globally, accounting for 1.8 million deaths in 2020. While the vast majority are caused by tobacco smoking, 15%−25% of all lung cancer cases occur in lifelong never-smokers. The International Agency for Research on Cancer (IARC) has classified multiple agents with sufficient evidence for lung carcinogenesis in humans, which include tobacco smoking, as well as several environmental exposures such as radon, second-hand tobacco smoke, outdoor air pollution, household combustion of coal and several occupational hazards. However, the IARC evaluation had not been stratified based on smoking status, and notably lung cancer in never-smokers (LCINS) has different epidemiological, clinicopathologic and molecular characteristics from lung cancer in ever-smokers. Among several risk factors proposed for the development of LCINS, environmental factors have the most available evidence for their association with LCINS and their roles cannot be overemphasized. Additionally, while initial genetic studies largely focused on lung cancer as a whole, recent studies have also identified genetic risk factors for LCINS. This article presents an overview of several environmental factors associated with LCINS, and some of the emerging evidence for genetic factors associated with LCINS. An increased understanding of the risk factors associated with LCINS not only helps to evaluate a never-smoker’s personal risk for lung cancer, but also has important public health implications for the prevention and early detection of the disease. Conclusive evidence on causal associations could inform longer-term policy reform in a range of areas including occupational health and safety, urban design, energy use and particle emissions, and the importance of considering the impacts of second-hand smoke in tobacco control policy.     

Epidemiology,Major Risk Factors and Genetic Predisposition for Breast Cancer in the Pakistani Population

Occurrence of breast cancer is related to genetic as well as cultural, environmental and life-style factors.Variations in diversity of these factors among different ethnic groups and geographical areas emphasize theimmense need for studies in all racial-ethnic populations. The incidence of breast cancer in Pakistan is highestin Asians after Jews in Israel and 2.5 times higher than that in neighboring countries like Iran and India,accounting for 34.6% of female cancers. The Pakistani population is deficient in information regarding breastcancer etiology and epidemiology, but efforts done so far had suggested consanguinity as a major risk factor forfrequent mutations leading to breast cancer and has also shed light on genetic origins in different ethnic groupswithin Pakistan. World-wide research efforts on different ethnicities have enhanced our understanding of geneticpredisposition to breast cancer but despite these discoveries, 75% of the familial risk of breast cancer remainsunexplained, highlighting the fact that the majority of breast cancer susceptibility genes remain unidentified.For this purpose Pakistani population provides a strong genetic pool to elucidate the genetic etiology of breastcancer because of cousin marriages. In this review, we describe the known breast cancer predisposition factorsfound in the local Pakistani population and the epidemiological research work done to emphasize the importanceof exploring factors/variants contributing to breast cance, in order to prevent, cure and decrease its incidencein our country.     

Health benefits and cost-effectiveness of primary genetic screening for Lynch syndrome in the general population

In current clinical practice, genetic testing to detect Lynch syndrome mutations ideally begins with diagnostic testing of an individual affected with cancer before offering predictive testing to at-risk relatives. An alternative strategy that warrants exploration involves screening unaffected individuals via demographic and family histories, and offering genetic testing to those individuals whose risks for carrying a mutation exceed a selected threshold. Whether this approach would improve health outcomes in a manner that is cost-effective relative to current standards of care has yet to be demonstrated. To do so, we developed a simulation framework that integrated models of colorectal and endometrial cancers with a 5-generation family history model to predict health and economic outcomes of 20 primary screening strategies (at a wide range of compliance levels) aimed at detecting individuals with mismatch repair gene mutations and their at-risk relatives. These strategies were characterized by (i) different screening ages for starting risk assessment and (ii) different risk thresholds above which to implement genetic testing. For each strategy, 100,000 simulated individuals, representative of the U.S. population, were followed from the age of 20, and the outcomes were compared with current practice. Findings indicated that risk assessment starting at ages 25, 30, or 35, followed by genetic testing of those with mutation risks exceeding 5%, reduced colorectal and endometrial cancer incidence in mutation carriers by approximately 12.4% and 8.8%, respectively. For a population of 100,000 individuals containing 392 mutation carriers, this strategy increased quality-adjusted life-years (QALY) by approximately 135 with an average cost-effectiveness ratio of $26,000 per QALY. The cost-effectiveness of screening for mismatch repair gene mutations is comparable to that of accepted cancer screening activities in the general population such as colorectal cancer screening, cervical cancer screening, and breast cancer screening. These results suggest that primary screening of individuals for mismatch repair gene mutations, starting with risk assessment between the ages of 25 and 35, followed by genetic testing of those whose risk exceeds 5%, is a strategy that could improve health outcomes in a cost-effective manner relative to current practice.     

Direct-to-Consumer Personal Genome Testing and Cancer Risk Prediction

ABSTRACT: The last several years has witnessed an explosion in genomics, with the advent of genome-wide association studies revealing hundreds of DNA variants significantly associated with most common diseases, including cancer. On the heels of these scientific advances came the direct-to-consumer (DTC) genetic testing industry. Genome-wide scans for disease have been marketed and sold directly to the public, without the involvement of a health care provider. Unlike genetic testing for mutations in known hereditary cancer susceptibility genes such as BRCA1/2, these genomic profiles examine DNA variants, which typically have a minimal risk impact, and account for only a fraction of the heritable component of cancer. Furthermore, risk information provided to consumers does not account for family history or other known risk factors. The clinical validity and utility of personal genome scans for disease risk prediction remain for the most part unestablished, although some argue lack of evidence of harm and the possibility that positive impacts on health behaviors or genetic awareness may result from consumer use. The DTC genetic testing industry has sparked significant controversy not only among the scientific community, but also among professional societies and government agencies.In this review, we present some of the history and methodological considerations of DTC genomic profiling, with a focus on cancer risk prediction. The literature regarding consumer awareness and utilization is explored, including understanding, expectations, and behavioral and psychological responses to DTC genomic risk prediction. Primary care provider and genetic professional knowledge and perceptions of DTC genomic profiling are also addressed. Ethical and scientific controversy surrounding the DTC genetic testing industry is presented, along with policy recommendations, regulatory actions, and the changing landscape of the DTC genetic testing market in response. Although our understanding of the human genome holds much promise in the realm of cancer prevention and treatment, DTC genomic profiling for cancer risk prediction is unlikely in its current form to have any significant impact on the health of the public. Time will tell if the next venture in genomic medicine, whole genome sequencing, will be accompanied by the translational research and emphasis on public/provider education required to ensure its successful application toward reducing the burden of cancer at a population level.     

Evidence That Established Lung Cancer Mortality Disparities in American Indians Are Not Due to Lung Cancer Genetic Testing and Targeted Therapy Disparities

BackgroundAmerican Indians and Alaska Natives (AI/AN) continue to experience extreme lung cancer health disparities. The state of Minnesota is home to over 70,000 AI/AN, and this population has a 2-fold increase in lung cancer mortality compared to other races within Minnesota. Genetic mutation testing in lung cancer is now a standard of high-quality lung cancer care, and EGFR mutation testing has been recommended for all adenocarcinoma lung cases, regardless of smoking status. However, genetic testing is a controversial topic for some AI/AN.Patients and MethodsWe performed a multisite retrospective chart review funded by the Minnesota Precision Medicine Grand Challenge as a demonstration project to examine lung cancer health disparities in AI/AN. We sought to measure epidemiology of lung cancer among AI receiving diagnosis or treatment in Minnesota cancer referral centers as well as rate of EGFR testing. The primary outcome was the rate of EGFR mutational analysis testing among cases and controls with nonsquamous, non–small-cell lung cancer. We secured collaborations with 5 health care systems covering a diverse geographic and demographic population.ResultsWe identified 200 cases and 164 matched controls from these sites. Controls were matched on histology, smoking status, sex, and age. In both groups, about one third of subjects with adenocarcinoma received genetic mutation testing.ConclusionThere was no significant difference in mutation testing in AI compared to non-AI controls at large health care systems in Minnesota. These data indicate that other factors are likely contributing to the higher mortality in this group.     

Identification of Genetic and Non-genetic Risk Factors for Nasopharyngeal Carcinoma in a Southeast Asian Population

Background: Nasopharyngeal carcinoma (NPC) is endemic in Southern Chinese and Southeast Asian populations. Geographical and ethnic clustering of the cancer is due to genetic, environmental, and lifestyle risk factors. This case-control study aimed to identify or confirm both genetic and non-genetic risk factors for NPC in one of the endemic countries, Malaysia. Materials and Methods: A panel of 768 single-nucleotide polymorphisms (SNPs) previously associated with various cancers and known non-genetic risk factors for NPC were selected and analyzed for their associations with NPC in a case-control study. Results: Statistical analysis identified 40 SNPs associated with NPC risk in our population, including 5 documented previously by genome-wide associationstudies (GWAS) and other case-control studies; the associations of the remaining 35 SNPs with NPC were novel.In addition, consistent with previous studies, exposure to occupational hazards, overconsumption of salt-cured foods, red meat, as well as low intake of fruits and vegetables were also associated with NPC risk. Conclusions: In short, this study confirmed and/or identified genetic, environmental and dietary risk factors associated with NPC susceptibility in a Southeast Asian population.     

Questionnaire study of cancer etiology in 503 children

Usefulness of an etiologic questionnaire was examined in an interview study of 503 children with cancer. The medical records of the children were abstracted, and their parents responded to a questionnaire-interview to identify genetic and environmental causes of cancer. Among 1,123 siblings of the index patients, 10 developed cancer as compared with 2 expected on the basis of cancer rates for the general population. Cancer risk factors were identified in individual patients with predisposing genetic and congenital disorders: neurofibromatosis (brain tumor), hereditary immunodeficiency (lymphoma), Down's syndrome (leukemia), XY gonadal dysgenesis (germ cell tumor), giant nevus (melanoma), and meningocele (sacral teratocarcinoma). Environmental causes of childhood cancer were difficult to discern because prior exposures were numerous, diverse, and usually ill defined. The questionnaire yielded more data than the medical record on gestational and family history and helped identify patients with exceptionally high cancer risk for additional investigation. Although the findings provide anecdotal confirmation of several associations, few original etiologic hypotheses were generated for formal testing with conventional epidemiologic techniques.     

Genetic factors in the etiology of breast cancer (author's transl)]

A review of literature shows that, at present, genetic factors are difficult to distinguish from environmental factors. A number of studies have put into light relationships between factors tranmetted genetically and an increased risk of breast cancer in some women. This might be a reflect of the transmission of a certain susceptibility. However, one of these factors alone cannot explain the increase of the risk. Most likely, as for many types of cancers, the development of breast cancer is due both to a multigenic transmission of a certain susceptibility and to the action of environmental factors. Though, epidemiological studies make possible to identify a high risk population. A regular follow-up of this population would permit early diagnosis and possibly prophylactic measures concerning the known environmental factors, and in particular hormonal factors.     

Factors Influencing Cancer Risk Perception in High Risk Populations: A Systematic Review

Background

Patients at higher than average risk of heritable cancer may process risk information differently than the general population. However, little is known about clinical, demographic, or psychosocial predictors that may impact risk perception in these groups. The objective of this study was to characterize factors associated with perceived risk of developing cancer in groups at high risk for cancer based on genetics or family history.

Methods

We searched Ovid MEDLINE, Ovid Embase, Ovid PsycInfo, and Scopus from inception through April 2009 for English-language, original investigations in humans using core concepts of "risk" and "cancer." We abstracted key information and then further restricted articles dealing with perceived risk of developing cancer due to inherited risk.

Results

Of 1028 titles identified, 53 articles met our criteria. Most (92%) used an observational design and focused on women (70%) with a family history of or contemplating genetic testing for breast cancer. Of the 53 studies, 36 focused on patients who had not had genetic testing for cancer risk, 17 included studies of patients who had undergone genetic testing for cancer risk. Family history of cancer, previous prophylactic tests and treatments, and younger age were associated with cancer risk perception. In addition, beliefs about the preventability and severity of cancer, personality factors such as "monitoring" personality, the ability to process numerical information, as well as distress/worry also were associated with cancer risk perception. Few studies addressed non-breast cancer or risk perception in specific demographic groups (e.g. elderly or minority groups) and few employed theory-driven analytic strategies to decipher interrelationships of factors.

Conclusions

Several factors influence cancer risk perception in patients at elevated risk for cancer. The science of characterizing and improving risk perception in cancer for high risk groups, although evolving, is still relatively undeveloped in several key topic areas including cancers other than breast and in specific populations. Future rigorous risk perception research using experimental designs and focused on cancers other than breast would advance the field.     

Predictive testing for BRCA1/2: attributes, risk perception and management in a multi-centre clinical cohort

The aim of this multi-centre UK study is to examine the attributes of a cohort offered predictive genetic testing for breast/ovarian cancer predisposition. Participants are adults unaffected with cancer from families with a known BRCA1/2 mutation. This is the first large multi-centre study of this population in the UK. The study evaluates mental health, perceived risk of developing cancer, preferred risk management options, and motivation for genetic testing. Participants were assessed when coming forward for genetic counselling prior to proceeding to genetic testing. Three hundred and twelve individuals, 76% of whom are female, from nine UK centres participated in the study. There are no gender differences in rates of psychiatric morbidity. Younger women (<50 years) are more worried about developing cancer than older women. Few women provide accurate figures for the population risk of breast (37%) or ovarian (6%) cancer but most think that they are at higher risk of developing breast (88%) and ovarian (69%) cancer than the average woman. Cancer related worry is not associated with perceived risk or uptake of risk management options except breast self-examination. The findings indicate that younger women may be particularly vulnerable at the time of the offer of a predictive genetic test.     

Genetische Epidemiologie am Beispiel Brustkrebs

Genetic epidemiology is a rapidly expanding research field, increasingly focusing on complex diseases such as diabetes, ischemic heart disease, asthma and cancer. Due to the multifactorial nature of common complex diseases, dissecting the genetic basis and understanding the role of genetic and environmental factors of disease occurrence in the population require not only the application of both linkage and association analysis, but also the adoption of well planned and adequately powered study designs with an appropriate population base. The central concepts in modern genetic epidemiology are reviewed and illustrated using the example of breast cancer. The breast cancer susceptibility genes BRCA1 and BRCA2, which are associated with high disease risk, were initially identified by linkage analysis in families with multiple affected members. Risk assessment for mutation carriers based on molecular genetic mutation screening is nevertheless not straightforward because cancer risks have been found to vary substantially depending on the population studied, the extent of family history and birth cohort. Estimates of breast cancer risk are higher in BRCA1/2 mutation carriers from families with multiple affected members than from the population-based studies. Furthermore, the large variability in age at diagnosis is consistent with a modification of risk due to other genetic and environmental factors. Large international studies have provided the first evidence that risk factors for breast cancer in the general population may similarly affect breast cancer in BRCA1/2 mutation carriers, but this needs confirmation in prospective studies. Mutations in BRCA1 and BRCA2 account for less than 20% of the genetic risk of breast cancer so that much of the unexplained familial risk is likely to be due to low to moderate penetrance alleles. Association studies to date, which have focused on putative functional variants in genes that are candidates because of their known biological function, have yielded few definitive common susceptibility alleles. Adequately powered studies for genome-wide association studies to identify further susceptibility genes and genetic effect modifiers associated with moderate risk and replication studies with necessitate international collaboration. Clinical studies on preventive measures in mutation carriers have been conducted in Germany in 12 specialised centres within a conjoint project funded by the German Cancer Aid. Studies on novel preventive therapies are currently being carried out at the national and international level.     

The impact of acculturation on awareness of genetic testing for increased cancer risk among Hispanics in the year 2000 National Health Interview Survey.

Previous studies suggest disparities in use of preventive cancer services among U.S. Hispanics are partly explained by knowledge and access factors. One area of emerging interest is uptake of genetic counseling and testing services by underserved populations. This study aims to estimate the percentage of Hispanics in five ethnic subgroups who are aware of genetic testing for inherited cancer risk, and to assess the influence of acculturation factors primarily related to language on test awareness. Weighted data from 4,313 Hispanic respondents (age >25 years) in the year 2000 National Health Interview Survey were analyzed. Overall, 20.6% of Hispanics had heard of genetic testing for cancer risk, with percentages highest among Puerto Ricans (27.3%) and lowest among Mexicans (14.3%). Completing the interview in Spanish and English [odds ratio (OR), 0.52; 95% confidence interval (95% CI), 0.35-0.78], or only Spanish (OR, 0.60; 95% CI, 0.42-0.86), was inversely associated with test awareness (reference group, only English). Having an intermediate (OR, 0.66; 95% CI, 0.48-0.90) or low (OR, 0.63; 95% CI, 0.39-1.01) level of English language preference was also inversely associated (reference, high level) whereas being born outside the United States was weakly associated (OR, 0.80; 95% CI, 0.57-1.11). Estimates were adjusted for age, education, ethnicity, parents' cancer history, health care access, and selected health behaviors and beliefs. Results of this national survey indicate that acculturation factors related to language may affect cancer genetic test awareness in Hispanics. These factors must be taken into account when informing individuals about the role of genetics in cancer risk and providing cancer genetic health services.     

Genetic testing in young women with breast cancer: results from a Web-based survey

BackgroundYoung women with breast cancer have an increased risk for harboring a BRCA1 or BRCA2 mutation. Frequency of genetic testing and factors associated with testing have not been well described in this population.Patients and methodsWe evaluated the rate of genetic testing among young breast cancer survivors identified through the Young Survival Coalition (YSC), an advocacy group for young women with breast cancer. Items regarding family history and genetic testing were included in a Web-based cross-sectional survey.ResultsA total of 701 women were eligible based on a history of breast cancer diagnosed ≤40 years. Mean age at diagnosis was 32.9 years and mean age at survey 35.7 years. About 41% reported a first- or second-degree relative with breast or ovarian cancer. About 24% had undergone genetic testing, and 26% of those tested reported that a mutation was found. By multivariate logistic regression, likelihood of having undergone testing was higher in women who were younger at diagnosis, were more educated, had a first- or second-degree relative with breast or ovarian cancer, had a mastectomy rather than breast conservation, and considered themselves at high risk for a cancer-predisposing mutation.ConclusionMost women diagnosed with breast cancer ≤40 years do not undergo genetic testing.     

Risk Factors for Cervical Cancer in Rural Areas of Wuhan China: a Matched Case-control Study

Cervical cancer is a serious public health problem in developing countries. We investigated possible riskfactors for cervical cancer in rural areas of Wuhan China using a matched case-control study with 33 womendiagnosed with cervical cancer and 132 healthy women selected from the same area as matched controls. Aquestionnaire, which included questions about general demography conditions, environmental and geneticfactors, the first sexual intercourse, first marriage age, age at first pregnancy, pregnancy first child’s age, femalepersonal health history, social psychological factors, dietary habits, smoking and alcohol status and other livinghabits was presented to all participants. At the same time, HPV infection of every participant was examined inlaboratory testing. Results showed HPV infection (P<0.000, OR=23.4) and pregnancy first child’s age (P<0.000,OR=13.1) to be risk factors for cervical cancer. Menopause (P=0.003, OR=0.073) was a protective factor againstcervical cancer. However, there was no indication of associations of environmental (drinking water, insecticide,disinfectant) genetic (cancer family history), or life-style factors (smoking status, alcohol status, physical training,sleep quality), including dietary habits (intake of fruit and vegetable, meat, fried food, bean products and pickledfood) or social psychological factors with cervical cancer. The results suggest that the risk of cervical cancer inChinese rural women may be associated with HPV infection, menopause and the pregnancy first child’s age.     

Risk estimation for breast cancer development; a clinical perspective

Breast cancer is the commonest cancer among women and the second highest cause of cancer death. It remains a significant health problem and represents a significant worry for many women and their physician. During the last years, intensive research has been focused on accurate risk estimation for breast cancer development. The aim of these efforts is to identify the "high-risk" group of women for breast cancer development. Preventive strategies (including intensive surveillance, chemoprevention, or prophylactic mastectomy) may be applied for the women at high risk for breast cancer development. Given the many management options, it seems reasonable that management of the high-risk woman be tailored to the level of risk she is willing to accept. In estimating the risk for breast cancer development, several factors should be taken into account (including age, reproductive factors, such as age at menarche and age at menopause or pregnancy and age at first live birth, history of benign breast lesions or breast cancer in situ [LCIS/DCIS], prior history of breast cancer, history of familiar or hereditary breast cancer, and environmental and lifestyle factors). Recently, quantitative risk estimation is possible by combining multiple risk factors into a comprehensible risk expression; this is of significant clinical importance, since it will reduce the considerable variation in management among health care providers. The Gail and the Claus model are the most widely used models for quantitative risk estimation. However, the clinician should understand that all models have some limitations that should be recalled as they are applied. It should be emphasized that risk assessment is a serious undertaking and should only be performed by those who have in-depth knowledge about risk factors, family pedigree analysis, comparative statistics, genetics susceptibility testing and the science of probability.