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Background/Objectives: B vitamins and related enzymes involved in one-carbon metabolism are necessary for DNA replication, DNA repair and regulation of gene expression. Disruption of one-carbon mechanism may affect cancer risk. We investigated prospectively the relationship between dietary intakes of methionine, B vitamins associated with one-carbon metabolism and risk of lung cancer. Subjects/Methods: The Melbourne Collaborative Cohort Study recruited 41 514 men and women aged 40-69 years between 1990 and 1994. During follow-up of 14 595 men and 22 451 women for an average of 15 years, we ascertained 348 incident lung cancers. Dietary intake of B vitamins and methionine was estimated from a 121-item food frequency questionnaire. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression. Results: In current smokers, dietary intake of riboflavin was inversely associated with lung cancer risk (HR = 0.53; 95% CI: 0.29-0.94, fifth versus first quintile;P-linear trend = 0.01). No associations were found for former or never smokers or for dietary intake of any of the other B vitamins or methionine. Conclusion: Overall, we found little evidence of an association between B vitamins or methionine and lung cancer risk. The weak inverse association between riboflavin and lung cancer risk in current smokers needs further investigation. European journal of Clinical Nutrition (2012) 66, 182-187; doi: 10.1038/ejcn.2011.157; published online 31 August 2011 Keywords: lung cancer; riboflavin; vitamin B6; vitamin B12; folate; methionine, Introduction One-carbon metabolism comprises a complex network of biochemical pathways, involving interactions between several B vitamins, homocysteine and methionine. Disruption of one-carbon metabolism can interfere with DNA replication, DNA repair [...]

Background/Objectives: Little is known about nutritional factors that influence circulating concentrations of steroid hormones, which are consistently associated with risk of breast cancer for postmenopausal women. We aimed to investigate the association between consumption of animal products and the plasma concentrations of steroid hormones and sex hormone-binding globulin (SHBG). Subjects/Methods: Cross-sectional analysis was conducted on plasma from 766 naturally postmenopausal women. We measured plasma concentrations of steroid hormones and SHBG, and estimated dietary intakes using a 121-item food frequency questionnaire. Log-transformed values of hormone concentrations were regressed on quartiles of intake of meat and dairy products among food items, and fats, proteins and cholesterol among nutrient intake. Results: Total red and fresh red meat consumption was negatively associated with SHBG levels (P for trend = 0.04 and < 0.01, respectively). Mean SHBG concentrations were ~8% and 13% lower for women in the highest quartile compared with the lowest quartile of total red and fresh red meat consumption, respectively. Positive associations were observed between dairy product consumption and total and free estradiol concentrations (P for trend = 0.02 and 0.03, respectively). Mean concentrations of total and free estradiol were 15 and 14% higher for women in the highest quartile of dairy product consumption than for those in the lowest quartile, respectively. No associations were observed with consumption of processed meat, chicken, fish, eggs, cholesterol, fats or protein. Conclusions: Our study suggests that greater consumption of total red and fresh red meat and dairy products might influence circulating concentrations of SHBG and estradiol, respectively. Confirmation and further investigation is required. European journal of Clinical Nutrition (2010) 64, 176-183; doi:10.1038/ejcn.2009.129.; published online 11 November 2009 Keywords: steroid hormones; animal products; fat; protein; postmenopausal women, Introduction High circulating concentrations of steroid hormones and low concentrations of sex hormone-binding globulin (SHBG) have been consistently associated with increased risk of postmenopausal breast cancer (Rock et al 2008). [...]

Dear Editor, Risk-prediction models, which include a combination of risk factors, have been developed as a more accurate way of estimating risk and personalizing preventive interventions. The Sneyd model for men, its predictors, the comparable variable in the AMFS dataset, the relative risk estimates and participants included in the external validation analyses. The Cho model, its predictors, the comparable variable in the AMFS dataset, the relative risk estimates and participants included in the external validation analyses..Table S2. [Extracted from the article]

Summary: Background: Melanoma risk prediction models could be useful for matching preventive interventions to patients' risk. Objectives: To develop and validate a model for incident first‐primary cutaneous melanoma using clinically assessed risk factors. Methods: We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case–Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole‐body naevi and solar lentigines, and self‐assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age‐ and sex‐adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer–Lemeshow test. Results: The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six‐level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 [95% confidence interval (CI) 2·71–4·54] in the Australian study and 2·56 (95% CI 2·23–2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76–0·83) in the Australian study and 0·73 (95% CI 0·70–0·75) in the Leeds study. The Hosmer–Lemeshow test P‐value was 0·30 in the Australian study and < 0·001 in the Leeds study. Conclusions: This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions. What's already known about this topic? Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels.For reasons of feasibility, time and cost many melanoma prediction models use self‐assessed risk factors. However, individuals tend to underestimate their naevus numbers. What does this study add? We present a melanoma risk prediction model, which includes clinically‐assessed whole‐body naevi and solar lentigines, and self‐assessed risk factors including pigmentation phenotype and history of keratinocyte cancer.This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions. Linked Comment: Toland. Br J Dermatol 2020; 182:1089–1090. Respond to this article Plain language summary available online [ABSTRACT FROM AUTHOR]

Background: People at high risk of developing melanoma are usually identified by pigmentary and naevus phenotypes. Objective: We examined whether associations of these phenotypes with melanoma risk differed by ambient sun exposure or participant characteristics in two population‐based, case–control studies with comparable ancestry but different ambient sun exposure. Methods: Data were analysed from 616 cases and 496 controls from the Australian Melanoma Family Study and 2012 cases and 504 controls from the Leeds (UK) case–control study. Questionnaire, interview and dermatological skin examination data were collected using the same measurement protocols. Relative risks were estimated as odds ratios using unconditional logistic regression, adjusted for potential confounders. Results: Hair and skin colour were the strongest pigmentary phenotype risk factors. All associations of pigmentary phenotype with melanoma risk were similar across countries. The median number of clinically assessed naevi was approximately three times higher in Australia than Leeds, but the relative risks for melanoma associated with each additional common or dysplastic naevus were higher for Leeds than Australia, especially for naevi on the upper and lower limbs. Higher naevus counts on the head and neck were associated with a stronger relative risk for melanoma for women than men. The two countries had similar relative risks for melanoma based on self‐reported naevus density categories, but personal perceptions of naevus number differed by country. There was no consistent evidence of interactions between phenotypes on risk. Conclusions: Classifying people at high risk of melanoma based on their number of naevi should ideally take into account their country of residence, type of counts (clinical or self‐reported), body site on which the naevus counts are measured and sex. The presence of naevi may be a stronger indicator of a genetic predisposition in the UK than in Australia based on less opportunity for sun exposure to influence naevus development. [ABSTRACT FROM AUTHOR]

Background: Few studies have examined the potentially reduced life expectancy associated with spinal pain (i.e. low back and neck pain) in an ageing population, particularly after controlling for familial factors, including genetics.Methods: We investigated whether spinal pain increased the rate of all-cause and disease-specific cardiovascular mortality in older Danish twins aged ≥70 years. Data from 4391 participants collected at baseline were linked with the Danish Cause of Death Registry with the study ending on 31 December 2014. Two crude and adjusted Cox proportional hazards regression analyses determined the rate of all-cause and disease-specific cardiovascular mortality by baseline spinal pain exposure; unpaired (total sample analysis) and twin pair (intra-pair analysis). Analyses were also adjusted for confounders; baseline physical functional ability and depressive symptoms. Competing risk regression models determined the rate of cardiovascular mortality, adjusting for similar confounders and using the total sample only.Results: Spinal pain was associated with an increased rate of all-cause mortality, hazard ratio (HR): 1.13 [95% confidence interval (CI): 1.06-1.21]. There was no association between spinal pain and cardiovascular disease mortality, sub-distribution hazard ratio (SHR): 1.08 [95% CI 0.96-1.21]. After adjusting for confounders (physical functional ability and depressive symptoms), the association became non-significant. All intra-pair analyses were statistically non-significant, although greater in magnitude for monozygotic twins.Conclusions: Older people reporting spinal pain have 13% increased risk of mortality per years lived but the connection is not causal. We found no association between spinal pain and cardiovascular-specific mortality. The influence of shared familial factors is unlikely.Significance: Older people reporting spinal pain have 13% increased risk of mortality per year lived. However, this association is not likely to be causal, with the relevant confounders contributing to this relationship. Thus, pain in the spine may be part of a pattern of poor health, which increases mortality risk in the older population. [ABSTRACT FROM AUTHOR]

Background: Heritability and population ‐ specific lifestyle factors are considered to significantly contribute to chronic low back pain (LBP), but traditional population studies fail to (1) adjust for genetics; and (2) use standard and validated definitions for LBP and for lifestyle factors. Methods: Using a classical and a co ‐ twin control study design and validated definitions for chronic LBP and lifestyle variables, we explored the relative contribution of genetics and environment on the prevalence of chronic LBP in a sample of adult Australian twins. Results: Data from 105 twin pairs showed that the prevalence of chronic LBP is significantly determined by genetic factors (heritability = 32%). Additionally, monozygotic twins were five times more likely to have chronic LBP than dizygotic twins when one of the siblings of the pair was affected. In a case ‐ control analysis (n = 38 twin pairs), an exploratory analysis showed higher prevalence of chronic LBP associated with light walking exercises and vigorous gardening or heavy work around the house. Daily time spent in sitting was also positively associated with chronic LBP, but not moderate physical activities such as jogging, cycling and gentle swimming. In the final multivariate model, only time spent in vigorous gardening or heavy work around the house remained associated with chronic LBP (odds ratio 6.5; 95% confidence interval 1.47–28.8). Conclusions: The type, frequency and duration of physical activity may be important to understand risk factors for chronic LBP. The causation path between chronic LBP and people's engagement in activities involving frequent bending and twisting such as gardening and housework should be further investigated. [ABSTRACT FROM AUTHOR]

Twin studies are becoming popular to investigate risk factors for low back pain ( LBP) because they consider the genetic factor and allow for more precise estimates of risks. We aimed to identify and summarize the results of studies based on twin samples investigating risk factors for LBP. The MEDLINE, CINAHL, LILACS, Web of Science and EMBASE databases were searched. Prospective and cross-sectional observational studies of LBP involving twins were included. The exposure factors could be genetics (heritability) or environmental such as smoking, alcohol consumption, body mass index and medical history. Pooling was attempted using an inverse variance weighting and fixed effects model. Twenty-seven studies were included. Estimates of heritability effects ranged from 21% to 67%. The genetic component was higher for more chronic and disabling LBP than acute and less disabling LBP. Smoking was significantly associated with LBP [pooled odds ratio ( OR) = 3.0; 95% confidence interval ( CI) 2.8-3.3] with a longitudinal and a cross-sectional study also identifying a dose-response relationship in people with chronic LBP. Obesity was associated with LBP (pooled OR = 1.9; 95% CI 1.6-2.2) with a cross-sectional study identifying a dose-response relationship. No association between alcohol consumption and LBP was identified. Co-morbidities such as asthma, diabetes and osteoarthritis were associated with LBP (pooled OR ranging from 1.6 to 4.2). The contribution of genetics to LBP appears to be dependent on the severity of the condition. Twin studies could be better used to explore possible causation paths between lifestyle factors, co-morbidities and LBP. [ABSTRACT FROM AUTHOR]

Background Growing pains ( GP) is a prevalent familial childhood disorder of unknown aetiology. Familial occurrence of GP, and individual and familial association of GP with restless legs syndrome ( RLS) has been reported. Methods We applied a twin family design to search for evidence of genetic susceptibility to GP, and for a genetic relationship between GP and RLS. The parents of 1843 twin pairs aged 3-16 years were administered a questionnaire, which identified 88 pairs with at least one twin individual fulfilling criteria for GP. Standard questionnaires for history of GP and RLS were completed for these twin pairs, their siblings and parents. Results Twenty-five of 34 monozygotic ( MZ) pairs were concordant for GP, compared with 12 of the 54 dizygotic ( DZ) pairs. The casewise concordance was 0.85 and 0.36 for MZ and DZ pairs, respectively ( p < 0.001). The lifetime GP prevalence for relatives of twins with GP was 51% for non-twin siblings, 47% for parents. Twenty-three percent of twin individuals with GP met RLS criteria compared with 8% of twin individuals without GP ( p = 0.03). Of the twins with GP concordance, 19% met RLS criteria compared with 2% of twins with GP discordance ( p = 0.01). In two MZ pairs, one had GP and the other RLS. The lifetime prevalence of RLS was 40% for mothers, and 24% for fathers and 18% for non-twin siblings. Conclusion This first twin family study of GP provides evidence for a genetic aetiology and for a genetic relationship to RLS. [ABSTRACT FROM AUTHOR]

Summary: Background: The aim of this analysis was to examine associations between lung health in childhood and mortality between ages 18 and 44 years in the Tasmanian Longitudinal Health Study (TAHS). Methods: The 1961 Tasmanian birth cohort who attended school in 1968 (n =8583) were linked to the Australian National Death Index (NDI) to identify deaths. Additional deaths were notified by families through a 37 year follow-up postal questionnaire. Information on lung health at age 7 years and on potential confounders was obtained from the original 1968 TAHS survey and school medical records. Cox proportional hazards modelling was used to assess determinants of mortality. Results: A total of 264 (3%) deaths were identified. The principal causes of death were external injury (56.1%, n =97) and cancer (17.9%, n =31). Males were more likely than females to have died (p =<0.1). Only two (1.1%) participants had died from respiratory conditions. Having an FEV1 <80% predicted at 7 years of age was associated with a 2-fold increased incidence of death. Tonsillectomy before age 7 years was associated with a 1.5-fold increase in mortality (p =0.05); being male with a 3.6-fold increase in mortality (p =0.0001); and repeated chest illnesses at age 7 years causing >30 days confinement in the last year, was associated with a 2.2-fold increase in mortality (p =0.03). Conclusions: Childhood lung health appears to be associated with increased mortality in adulthood, perhaps by affecting the ability to survive trauma, major illnesses and other physical stresses. [Copyright &y& Elsevier]

The ATM gene variants segregating in ataxia-telangiectasia families are associated with increased breast cancer risk, but the contribution of specific variants has been difficult to estimate. Previous small studies suggested two functional variants, c.7271T>G and c.1066-6T>G (IVS10-6T>G), are associated with increased risk. Using population-based blood samples we found that 7 out of 3,743 breast cancer cases (0.2%) and 0 out of 1,268 controls were heterozygous for the c.7271T>G allele (P=0.1). In cases, this allele was more prevalent in women with an affected mother (odds ratio [OR]=5.5, 95% confidence interval [CI]=1.2-25.5; P=0.04) and delayed child-bearing (OR=5.1; 95% CI=1.0-25.6; P=0.05). The estimated cumulative breast cancer risk to age 70 years (penetrance) was 52% (95% CI=28-80%; hazard ratio [HR]=8.6; 95% CI=3.9-18.9; P<0.0001). In contrast, 13 of 3,757 breast cancer cases (0.3%) and 10 of 1,268 controls (0.8%) were heterozygous for the c.1066-6T>G allele (OR=0.4; 95% CI=0.2-1.0; P=0.05), and the penetrance was not increased (P=0.5). These findings suggest that although the more common c.1066-6T>G variant is not associated with breast cancer, the rare ATM c.7271T>G variant is associated with a substantially elevated risk. Since c.7271T>G is only one of many rare ATM variants predicted to have deleterious consequences on protein function, an effective means of identifying and grouping these variants is essential to assess the contribution of ATM variants to individual risk and to the incidence of breast cancer in the population. Hum Mutat 27(11), 1122-1128, 2006. Published 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: To investigate the genetic and environmental influences on adult body size, shape, and composition in women and men, and to assess the impact of age. MATERIALS AND METHODS:: In this cross-sectional study of 325 female and 299 male like-sex healthy twin pairs, on average 38?y old (18-67?y), we determined zygosity by DNA similarity, and performed anthropometry and bioelectrical impedance analysis of body composition. The contribution to the total phenotypic variance of genetic, common environment, and individual environment was estimated in multivariate analysis using the FISHER program. Further, these variance components were analysed as linear functions of age. RESULTS:: In both women and men genetic contributions were significant for all phenotypes. Heritability for body mass index was 0.58 and 0.63; for body fat%, 0.59 and 0.63; for total skinfolds, 0.61 and 0.65; for extremity skinfolds 0.65 and 0.62; for truncal skinfolds, 0.50 and 0.69; for suprailiac skinfolds, 0.49 and 0.48; for waist circumference, 0.48 and 0.61; for hip, 0.52 and 0.58; for lean body mass/height2, 0.61 and 0.56; and for height, 0.81 and 0.69, respectively. There was no strong evidence of common environmental effects under the assumptions of no nonadditive effect. The pattern of age trends was inconsistent. However, when significant there was a decrease in heritability with advancing age. DISCUSSION:: These findings suggest that adult body size, shape, and composition are highly heritable in both women and men, although a decreasing tendency is seen with advancing age.International Journal of Obesity (2004) 28, 39-48. doi:10.1038/sj.ijo.0802524 Published online 11 November 2003 [ABSTRACT FROM AUTHOR]

The epidemiology of androgenetic alopecia (AGA) is not fully understood. Although a strong genetic basis has long been identified, little is known of its non-genetic causes. To estimate the prevalence of and to determine risk factors for AGA in men aged 40–69 years in Australia. Men ( n = 1390) were recruited at random from the electoral rolls to serve as controls in a population-based case–control study of prostate cancer. All were interviewed in person and direct observations of AGA were made. Men were grouped into the following categories; no AGA, frontal AGA, vertex AGA and full AGA (frontal and vertex AGA). Epidemiological data collected from these men were used for an analysis of risk factors for each AGA category using unconditional logistic regression with AGA category as the response variable adjusting for age, education and country of birth. The prevalence of vertex and full AGA increased with age from 31% (age 40–55 years) to 53% (age 65–69 years). Conversely, the proportion of men with only frontal AGA was very similar across all age groups (31–33%). No associations were found between pubertal growth spurt or acne, reports of adult body size at time of interview, urinary symptom score, marital status, or current smoking status or duration of smoking and the risk of any form of AGA. The consumption of alcohol was associated with a significant increase in risk of frontal and vertex AGA but not full AGA. Men with vertex AGA had fewer female sexual partners but average ejaculatory frequency did not differ between men in different AGA categories. Reported weight and lean body mass at reaching maturity at about 21 years of age were negatively associated with vertex balding ( P for trend < 0·05) but not with frontal AGA or full AGA. Evidence for environmental influences on AGA remains very slight. Our study failed to confirm previously reported or hypothesized associations with smoking and benign prostatic hypertrophy. The associations that we found with alcohol consumption and with lean body mass at age 21 years would be worthy of further research if they were able to be replicated in other studies. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess whether prostate cancer might be related to hormone levels and, by inference, to differences in sexual activity. PATIENTS, SUBJECTS AND METHODS In a case-control study of men with prostate cancer aged < 70 years at diagnosis and age-matched control subjects, information was collected on two aspects of sexual activity; the number of sexual partners and the frequency of total ejaculations during the third to fifth decades of life. RESULTS There was no association of prostate cancer with the number of sexual partners or with the maximum number of ejaculations in 24 h. There was a negative trend (P < 0.01) for the association between risk and number of ejaculations in the third decade, independent of those in the fourth or fifth. Men who averaged five or more ejaculations weekly in their 20s had an odds ratio (95% confidence interval) of 0.66 (0.49–0.87) compared with those who ejaculated less often. CONCLUSIONS The null association with the number of sexual partners argues against infection as a cause of prostate cancer in this population. Ejaculatory frequency, especially in early adult life, is negatively associated with the risk of prostate cancer, and thus the molecular biological consequences of suppressed or diminished ejaculation are worthy of further research. [ABSTRACT FROM AUTHOR]

Describes a study to determine whether premenopausal daughters of women with postmenopausal osteoporosis have lower bone mass than other women of the same age. Study details; Results; Conclusions.

Summary: 黑色素瘤是一种在黑素细胞(皮肤的色素细胞)中发生的癌症。黑色素瘤发生率(表示其常见程度)在皮肤白皙人群中增加,其中澳大利亚、新西兰、北美和欧洲的发病率最高。 在澳大利亚,14 名男性中有 1 名和 24 名女性中有 1 名将在其一生中被诊断患有黑色素瘤。黑色素瘤的危险因素包括日晒、日光浴、皮肤上痣的数量、皮肤对阳光的敏感度、雀斑数量、肤色、眼睛颜色、头发颜色、家族史和许多易感基因(使您面临更高风险的基因)。 黑色素瘤风险预测模型(将许多个体黑色素瘤危险因素结合到总体风险中)可能有助于通过匹配预防策略(干预)与患者的黑色素瘤风险水平来预防黑色素瘤。 许多黑色素瘤风险预测模型使用自我评估的危险因素,因为与临床(医学)危险因素评估相比,这样更快且成本更低,但很多人低估了他们的痣数。本研究旨在推导一个黑色素瘤风险预测模型,其中包括身上痣的数量和日光性雀斑痣(阳光引起的深色皮肤斑)作为临床评估的危险因素,以及色素(肤色)特征、日晒、家族史和皮肤癌病史作为自我评估的危险因素。 痣的数量是模型中最强的危险因素。该模型在识别能力(模型区分患有和未患黑色素瘤的个体的能力)方面表现出色。在临床环境中,该模型可能有助于临床医生根据患者的黑色素瘤风险确定适合针对性预防策略的患者。 本摘要涉及研究:一项关于纳入临床评估的痣和日光性雀斑痣的黑色素瘤风险预测模型的开发和外部验证研究 Linked Article: Vuong et al. Br J Dermatol 2020; 182:1262–1268 [ABSTRACT FROM AUTHOR]

Summary: Melanoma is a cancer that develops in the melanocytes, the pigment cells of the skin. Melanoma incidence rates, which show how common it is, have been increasing in people with fair skin, with the highest rates in Australia, New Zealand, North America and Europe. In Australia, one in 14 men and one in 24 women will be diagnosed with melanoma during their lifetime. Risk factors for melanoma include sun exposure, sunbed use, the number of moles on the skin, the skin's sensitivity to the sun, the number of freckles, skin colour, eye colour, hair colour, family history and a number of susceptibility genes (genes that place you at higher risk). Melanoma risk prediction models, which combine many individual melanoma risk factors into an overall risk, may be useful in the prevention of melanoma by matching prevention strategies (interventions) to the patient's melanoma risk levels. Many melanoma risk prediction models use self‐assessed risk factors because it is quicker and less costly compared to the clinical (medical) assessment of risk factors, but many people underestimate the number of moles they have. This study aims to derive a melanoma risk prediction model, which includes the number of moles on the body and solar lentigines (darker skin patches caused by the sun) as clinically‐assessed risk factors, and pigmentation (skin colour) characteristics, sun exposure, family history and history of skin cancer as self‐assessed risk factors. The number of moles is the strongest risk factor in the model. The model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma. In a clinical setting, this model may help clinicians identify patients for targeted prevention strategies based on the patient's melanoma risk. This is a summary of the study: Development and external validation study of a melanoma risk prediction model incorporating clinically assessed naevi and solar lentigines Linked Article: Vuong et al. Br J Dermatol 2020; 182:1262–1268 [ABSTRACT FROM AUTHOR]

We used data from 765 cases and 564 controls in the population-based Australian Breast Cancer Family Study to investigate whether, in women under the age of 40, the profile of risk factors differed between breast cancer subtypes defined by joint oestrogen and progesterone receptor status. As hypothesised, no significant differences were found. [ABSTRACT FROM AUTHOR]

The authors discuss zygosity testing in same-sex twins. Topics discussed include the false assumptions that all dichorionic twin pairs are dizygotic (DZ) and that monozygotic (MZ) twins must be physically identical, studies which show why zygosity knowledge is medically important, and the need for all same-sex twins to undergo zygosity testing.

Many genetic epidemiology resources have collected dried blood spots (predominantly as Guthrie Cards) as an economical and efficient means of archiving sources of DNA, conferring great value to genetic screening methods that are compatible with this medium. We applied Hi-Plex to screen the breast cancer predisposition gene PALB2 in 93 Guthrie Card-derived DNA specimens previously characterized for PALB2 genetic variants via DNA derived from lymphoblastoid cell lines, whole blood, and buffy coat. Of the 93 archival Guthrie Card-derived DNAs, 92 (99%) were processed successfully and sequenced using approximately half of a MiSeq run. From these 92 DNAs, all 59 known variants were detected and no false-positive variant calls were yielded. Fully 98.13% of amplicons (5417/5520) were represented within 15-fold of the median coverage (2786 reads), and 99.98% of amplicons (5519/5520) were represented at a depth of 10 read-pairs or greater. With Hi-Plex, we show for the first time that a High-Plex amplicon-based massively parallel sequencing (MPS) system can be applied effectively to DNA prepared from dried blood spot archival specimens and, as such, can dramatically increase the scopes of both method and resource. [ABSTRACT FROM AUTHOR]

Abstract: Background: Few data exist regarding the use of complementary and alternative medicine (CAM) by unaffected women at high risk of breast cancer. Methods: Self-reported CAM use by women from multiple-case breast cancer families was obtained by questionnaire. Factors associated with CAM use were assessed using multiple logistic regression. Results: Of 892 women, 55% (n =489) used CAM, 6% (n =53) specifically to prevent cancer. CAM use was independently associated with tertiary education level (OR 2.56, 95% CI 1.83–3.58, p <0.001), greater physical activity (OR 1.05 per hour of physical activity/week, 95% CI 1.00–1.10, p =0.049), greater anxiety (OR 1.92, 95% CI 1.16–3.16, p =0.01), not currently smoking (OR 0.64, 95% CI 0.42–0.97, p =0.037) and lower perceived BC risk (OR 0.82 per 20 percentage points, 95% CI 0.72–0.94, p =0.005). Conclusions: The majority of high-risk women use CAM, but mostly for reasons other than cancer prevention. Most predictors of CAM use are consistent with the limited literature for women at high risk for cancer. [Copyright &y& Elsevier]

Abstract: Women diagnosed with breast cancer before the age of 40 years who have a strong family history of breast and/or ovarian cancer were selected from an Australian population-based case-control-family study for large deletion screening within the BRCA1 promoter. Deletions within the BRCA1 promoter region are usually not detected by the methods applied in routine clinical mutation detection strategies. Fifty-one of the 66 women (77%) who met our inclusion criteria were tested for promoter deletions using linkage disequilibrium analysis of two BRCA1 polymorphic sites (C/G1802 and Pro871Leu) and multiplex ligation-dependent probe amplification. Two cases of BRCA1 promoter deletion involving exons 1A-2 and exons 1A-23 were detected. The morphology of the breast cancers arising in these women with BRCA1 promoter deletions was consistent with the morphology associated with other germline BRCA1 mutations. Large genomic deletions that involve the promoter regions of BRCA1 make up 20% (2/10) of all known BRCA1 mutations in this group of young women with a strong family history of breast and ovarian cancer. Our data support the inclusion of testing for large genomic alterations in the BRCA1 promoter region in routine clinical mutation detection within BRCA1. [Copyright &y& Elsevier]