Analytical relationship between family history and genetic and environmental risks, with application to female breast cancer

It is well established in genetic epidemiology that family history is an important indicator of familial aggregation of disease in a family. A strong genetic risk factor or an environmental risk factor with high familial correlation can result in a strong family history. In this paper, family history refers to the number of first-degree relatives affected with the disease. Cui and Hopper (Journal of Epidemiology and Biostatistics 2001; 6: 331-342) proposed an analytical relationship between family history and relevant genetic parameters. In this paper we expand the relationship to both genetic and environmental risk factors. We established a closed-form formula for family history as a function of genetic and environmental parameters which include genetic and environmental relative risks, genotype frequency, prevalence and familial correlation of the environmental risk factor. The relationship is illustrated by an example of female breast cancer in Australia. For genetic and environmental relative risks less than 10, most of the female breast cancer cases occur between the age of 40 and 60 years. A higher genetic or environmental relative risk will move the peak of the distribution to a younger age. A more common disease allele or more prevalent environmental risk factor will move the peak to an older age. For a proband with breast cancer, it is most likely (with probability ge80%) that none of her first-degree relatives is affected with the disease. To enable the probability of having a positive family history to reach 50%, the environmental relative risks must be extremely as high as 100, the familial correlation as high as 0.8 and the prevalence as low as 0.1. For genetic risk alone, even the relative risk is as high as 100, the probability of having a positive family history can only reach about 30%. This suggests that the environmental risk factor seems to play a more important role in determining a strong family history than the genetic risk factor.

Risk of prostate cancer associated with a family history in an era of rapid increase in prostate cancer diagnosis (Australia)

OBJECTIVE: We conducted a case-control study of prostate cancer and familial risk of the disease in Australia between 1994 and 1998, a period during which the incidence of prostate cancer increased dramatically with widespread use of prostate-specific antigen (PSA) testing. METHODS: 1475 cases and 1405 controls were asked about prostate cancer in their first-degree relatives. Odds ratios (OR) were calculated using logistic regression. RESULTS: Cases were more likely to report a family history of prostate cancer than controls (OR 3.0; 95% confidence interval (CI) 2.3-3.9) and cases reporting an affected relative were younger (58.8 versus 60.9 years, p < 0.0001). The OR for an affected first-degree relative increased with increasing number of affected relatives and decreased with increasing age of the case. The OR for more than one affected first-degree relative was 6.9 (95% CI 2.7-18). The OR for an affected brother was 3.9 (95% CI 2.5-6.1) and for an affected father was 2.9 (95% CI 2.1-3.9) but these were not significantly different (p = 0.2). When analyses were repeated including only diagnoses made in relatives prior to 1992, the risks were generally similar except that the OR for an affected brother decreased to 3.1 (95% CI 1.2-3.9). When only relatives' diagnoses made after 1991 were included results were again similar to those for all relatives, although the effect for brothers was greater and the attenuation with age at diagnosis dissipated. CONCLUSIONS: The recent introduction of PSA testing that has resulted in a greater prevalence of apparent prostate cancer, does not appear to have substantially altered familial risks of disease, although effects associated with brothers may be inflated.

Risk perception, risk communication and message framing : breast cancer and family history

Examines the relationships between risk perception, risk communication, and health protective behaviour in relation to breast cancer and family history. Qualitative research was conducted to develop a printed community resource. Theoretical and practical implications for health behaviour theory and risk communication are identified.

Family history and the Great War in Australia

The boom in family history that is a hallmark of so much historical activity around the globe over the last three decades is one contributor to the resurgence of interest in the Great War itself. In Australia, as elsewhere in the western world, family history and the resources dedicated to it have been expanding rapidly. This chapter investigates recent practices of family history of the Great War in Australia. Our aim is to examine the role of family history in producing and reproducing knowledge of the Great War within Australian families, and the relationship between the conduct and transmission of family history on the one hand, and the contours of cultural memory on the other.

No evidence of genetic anticipation in a large family with Lynch syndrome.

Lynch syndrome is the commonest inherited cause of colorectal cancer (CRC). Genetic anticipation occurs when the age of onset of a disorder decreases in successive generations. It is controversial whether this occurs in Lynch syndrome. Previous studies have included heterogenous groups of subjects from multiple families, including subjects with a clinical diagnosis (based on family history) as well as those with proven germline mismatch repair gene mutations. The purpose of this study was to determine whether genetic anticipation occurs in mismatch repair gene carriers from a single Lynch syndrome family. This study includes members of a single family known to carry an MLH1 gene mutation who are proven germline mutation carriers or obligate carriers (based on their offspring's mutation status). Evidence of genetic anticipation (determined by age of onset of first CRC) was sought in two ways: Firstly, subjects were grouped as parent-child pairs and individuals were compared with their own offspring; secondly they were grouped by generation within the family tree. The Kaplan-Meier technique was used to adjust for variable follow up times. The family tree consisted of 714 subjects. Ninety-two subjects over five generations were included in the study. There was no evidence of genetic anticipation over the generations. (P = 0.37). Similarly, in the 75 parent-child pairs identified, age of onset of CRC was similar for parents and children (P = 0.51). We could not identify any evidence of genetic anticipation in mutation carriers from a single family with Lynch syndrome.

Exploring family and community involvement to protect Thai youths from alcohol and illegal drug abuse

Youth substance abuse is widely recognized as a major public health issue in Thailand. This study explores family and community risk and protective factors relevant to alcohol and illegal drug misuse in 1,778 Thai teenagers. Strong family attachment and a family history of antisocial behaviors were strongly associated with nearly all forms of substance abuse, with adjusted odds ratios ranging from 5.05 to 8.45. Community disorganization was strongly associated with self-reported substance use, although involvement in prosocial activities acted as a protective factor. The findings suggest that interventions that promote family cohesion and encourage community involvement may have considerable benefits in reducing substance abuse in Thai adolescents.

Parent and family factors associated with service use by young people with mental health problems: a systematic review

AIM: To conduct a systematic review of parent and family factors associated with service use for young people with mental health problems, to inform early intervention efforts aimed at increasing service use by young people. METHODS: A systematic search of academic databases was performed. Articles were included in the review if they had: a sample of young people aged between 5 and 18 years; service use as the outcome measure; one or more parental or family variables as a predictor; and a comparison group of non-service using young people with mental health problems. In order to focus on factors additional to need, the mental health symptoms of the young person also had to be controlled for. Stouffer's method of combining P-values was used to draw conclusions as to whether or not associations between variables were reliable. RESULTS: Twenty-eight articles were identified investigating 15 parental or family factors, 7 of which were found to be associated with service use for a young person with mental health needs: parental burden, parent problem perception, parent perception of need, parent psychopathology, single-parent household, change in family structure and being from the dominant ethnic group for the United States specifically. Factors not found to be related to service use were: family history of service use, parent-child relationship quality, family functioning, number of children, parent education level, parent employment status, household income and non-urban location of residence. CONCLUSIONS: A number of family-related factors were identified that can inform effective interventions aimed at early intervention for mental health problems. Areas requiring further research were also identified.

Effects of message framing on breast-cancer-related beliefs and behaviours: the role of mediating factors

The effects of gain-loss message framing on breast-cancer-related cognitions and behaviors were assessed among 539 women aged 30 to 70 years. The design involved a prebrochure telephone interview, followed by a brochure mailout, and a postbrochure telephone interview. The brochures contained information about breast cancer and the risk of family history. Recommended behaviors were framed to emphasize gains, losses, or were neutral; and statistical risk information was presented either positively or negatively. Measures included demographics, family history, breast self-examination (BSE) performance, BSE intention, self-efficacy in performing BSE, perceived early detection risk of breast cancer, perceived susceptibility to breast cancer, and anxiety about breast cancer. A loss-framed message led to greater positive change in BSE behavior. Interactions between framing effects and variables of issue involvement, perceived early detection risk, and self-efficacy indicated effects on behavior, but not beliefs.

Women's perceptions of familial aspects of breast cancer

Women’s understanding of familial aspects of breast cancer was examined using both focus groups and interviews. The studies covered issues related to perceptions of breast cancer risk factors, perceived breast cancer risk, understanding of risk information, and family history of breast cancer as a risk factor. Study 1 consisted of four focus group discussions with women from the general community. Study 2 comprised ten face-to-face interviews with women who had a family history of breast cancer. The results in combination indicate a fairly high level of awareness of family history as a risk factor for breast cancer. However, the definition of a familial history of breast cancer differed between the groups, with those without a family history being more inclusive than those with such a history. The paper concludes with suggestions for use by those developing resources materials for those with a familial history of breast cancer.

Risk factors for surgically treated benign prostatic hyperplasia in Western Australia

Objective: To determine the relationship between personal, hormonal and lifestyle risk factors and surgically treated benign prostatic hyperplasia (BPH). Materials and methods: A population-based case–control study was conducted in Western Australia (WA) on men aged 40–75 years who were surgically treated at public and private hospitals for BPH during 2001–2002. Controls were recruited from the WA electoral roll. Cases and controls were compared with regard to demographic and lifestyle factors and proxy measures of hormonal status using logistic regression. Data were available for 398 cases and 471 controls. Results: No associations with BPH were found for family history of prostate cancer in father or brother, serving in the military in a combat area, pattern of baldness, smoking status, obesity, alcohol intake and occupational physical activity. The only inverse relationship was observed with heavy alcohol drinking (>30 g/day), however, this was not statistically significant. An increased risk of BPH, not statistically significant, was observed for British-born men compared to Australian born and for history of vasectomy. The analysis was repeated after excluding 28% of controls with moderate and severe symptoms of BPH and 7% of cases with mild symptoms prior to surgery, and our results remained essentially unchanged. Conclusions:The results suggest that there are few risk factors for BPH although perhaps country of birth, vasectomy and heavy alcohol consumption may be considered further.

After hMSH2 and hMLH1- what next? Analysis of three-generational, population-based, early-onset colorectal cancer families

The aim of our study was to examine the role of genetic factors on early-onset colorectal cancer after excluding the impact of germline mutations in the two major mismatch repair genes. A total of 131 incident probands, under 45 years at diagnosis of a first primary colorectal cancer selected from the Victorian Cancer Registry, and their first-and second-degree relatives, were interviewed. Germline DNA from all 12 probands with a family history meeting the modified Amsterdam Criteria for Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and a random sample of 31 of the remaining probands was screened for mutations in hMSH2 and hMLH1 via manual sequencing. Germline mutations were identified in 6 of the 131 probands (5%), all from the "HNPCC" families. Of the remaining 125 probands, 51 (41%) reported at least one first-or second-degree relative with colorectal cancer with an excess of colorectal cancer in first-degree relatives (SMR = 2.7, 95% CI = 1.7-4.1, p < 0.001). The lifetime risk to age 70 for first-degree relatives was 8.0% (5.0-12.8%), compared to the Victorian population risk of 3.2% (p = 0.01). The best fitting major gene model was a recessively-inherited risk of 98% to age 70 (95% CI = 24-100%) carried by 0.17% of the population and would explain 15% of all colorectal cancer in cases with a diagnosis before age 45. Early-onset colorectal cancer is strongly familial even after excluding families found to be segregating a mutation in either of the 2 major mismatch repair genes. There is evidence for a role of yet to be identified genes associated with a high recessively-inherited risk of colorectal cancer.

Meat consumption among 18-month-old children participating in the Childhood Asthma Prevention Study

Objective: To document meat consumption among 18-month-old children, for use in refining population dietary assessment methods and dietary guidance for young children.

Design: A secondary analysis of data collected in 1998-2000 from the 18 months follow up of the Childhood Asthma Prevention Study: an intervention trial of omega-3 oil supplementation and house-dust mite reduction, from birth to five years.

Subjects and setting: Pregnant women whose unborn children had an atopic family history were recruited from antenatal clinics of six hospitals in western Sydney. Carers of 429 18-month-old children (80% response) satisfactorily completed three-day weighed food records.

Main outcome measures: Mean and median intakes per day and portion sizes of various meats and meat products.

Statistical analyses: T-tests for comparing gender differences; Pearson correlation and one-way analysis of variance for relationships between meat and nutrient intake.

Results: During the recording period 94% of the children ate meat. McDonald's Chicken McNuggets^TM, beef mince, and beef sausages were the most frequently consumed meats. Median portion sizes ranged from 20-50 g, and were considerably smaller than 'usual' portions specified on food frequency questionnaires in common use. Higher meat diets in this age group were not associated with higher intakes of iron or zinc per MJ.

Conclusion: The marginally low intakes of iron and zinc in this age group could be improved by greater use of cuts of red meat appropriately prepared for toddlers.

Consumption of 'extra' foods (energy-dense, nutrient poor) among children aged 16-24 months from western Sydney, Australia

Objective: This study evaluates the contribution of energy-dense, nutrient-poor ‘extra’ foods to the diets of 16–24-month-old children from western Sydney, Australia.

Design:   An analysis of cross-sectional data collected on participants in the Childhood Asthma Prevention Study (CAPS), a randomised trial investigating the primary prevention of asthma from birth to 5 years. We collected 3-day weighed food records, calculated nutrient intakes, classified recorded foods into major food groups, and further classified foods as either ‘core’ or ‘extras’ according to the Australian Guide to Healthy Eating.

Setting:  Pregnant women, whose unborn child was at risk of developing asthma because of a family history, were recruited from all six hospitals in western Sydney, Australia. Data for this study were collected in clinic visits and at participants’ homes at the 18-month assessment.

Participants: Four hundred and twenty-nine children participating in the CAPS study; 80% of the total cohort.

Results:  The mean consumption of ‘extra’ foods was xs223C150 g day− 1 and contributed 25–30% of the total energy, fat, carbohydrate and sodium to the diets of the study children. ‘Extra’ foods also contributed around 20% of fibre, 10% of protein and zinc, and about 5% of calcium. Children in the highest quintile of ‘extra’ foods intake had a slightly higher but not significantly different intake of energy from those in the lowest quintile. However, significant differences were evident for the percentage of energy provided by carbohydrate and sugars (higher) and protein and saturated fat (lower). The intake of most micronutrients was also significantly lower among children in the highest quintile of consumption. The intake of ‘extra’ foods was inversely associated with the intake of core foods.

Conclusions:  The high percentage of energy contributed by ‘extra’ foods and their negative association with nutrient density emphasise the need for dietary guidance for parents of children aged 1–2 years. These preliminary data on commonly consumed ‘extra’ foods and portion sizes may inform age-specific dietary assessment methods.

Skin prick test can identify eczematous infants at risk of asthma and allergic rhinitis

Background: Assessment of allergic sensitization is not routinely performed in infants and young children with eczema.

Objective: To determine whether infants who have atopic eczema (with sensitization) are at a greater risk of developing asthma and allergic rhinitis (AR) than those with non-atopic eczema (without concurrent sensitization).

Methods: The presence of eczema was prospectively documented until 2 years of age in a birth cohort of 620 infants with a family history of atopic disease. Sensitization status was determined by skin prick tests (SPTs) at 6, 12, and 24 months using six common allergens. Interviews were conducted at 6 and 7 years to determine the presence of asthma and AR.

Results: Within the first 2 years of life, 28.7% of the 443 children who could be classified had atopic eczema: 20.5% had non-atopic eczema, 19.0% were asymptomatic but sensitized and 31.8% were asymptomatic and not sensitized. When compared with children with non-atopic eczema in the first 2 years of life, children with atopic eczema had a substantially greater risk of asthma [odds ratio (OR)=3.52, 95% confidence interval=1.88–6.59] and AR (OR=2.91, 1.48–5.71). The increased risk of asthma was even greater if the infant had a large SPT (OR=4.61, 2.34–9.09) indicative of food allergy. There was no strong evidence that children with non-atopic eczema had an increased risk of asthma or AR compared with asymptomatic children.

Conclusion: In children with eczema within the first 2 years of life, SPT can provide valuable information on the risk of childhood asthma and AR.