Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture

Ionizing radiation and breast cancer in men (United States)

The purposes of this study were to determine whether exposure of the vestigial male breast to ionizing radiation is associated with an increase in risk of breast cancer and, if so, to determine whether the apparent effects on risk in men are similar to those reported for women. A population-based case-control study of breast cancer in men was conducted in 10 geographic areas of the United States. Information on possible prior exposure to ionizing radiation, and on other potential risk factors for breast cancer, was obtained from personal interviews of 227 cases and 300 controls who were recruited from October 1983 to September 1986. Evidence from this study that ionizing radiation can cause breast cancer in men includes: a modest trend of increasing risk with frequency of chest X-rays; an increase in risk in men with three or more radiographic examinations, especially if received prior to 1963; and an increase in risk in men who received X-ray treatments to the chest and adjacent body areas. Risk was increased only from 20 to 35 years after initial exposure from either radiographic examinations or X-ray treatments, and declined after three to four decades since last exposure, suggesting a wave of increased risk of finite duration following exposure. The doses of radiation received could not be estimated precisely, but those from diagnostic procedures were likely similar to those received by prepubertal females in prior studies, and the results of those and the present investigation are compatible. The carcinogenic effects of ionizing radiation may be similar in the male and prepubertal female breast. © 1994 Rapid Communications of Oxford Ltd

Isolation and characterization of Ty1-copia retrotransposon sequences in the blue agave (Agave tequilana Weber var. azul) and their development as SSAP markers for phylogenetic analysis

The purposes of this study were to determine whether exposure of the vestigial male breast to ionizing radiation is associated with an increase in risk of breast cancer and, if so, to determine whether the apparent effects on risk in men are similar to those reported for women. A population-based case-control study of breast cancer in men was conducted in 10 geographic areas of the United States. Information on possible prior exposure to ionizing radiation, and on other potential risk factors for breast cancer, was obtained from personal interviews of 227 cases and 300 controls who were recruited from October 1983 to September 1986. Evidence from this study that ionizing radiation can cause breast cancer in men includes: a modest trend of increasing risk with frequency of chest X-rays; an increase in risk in men with three or more radiographic examinations, especially if received prior to 1963; and an increase in risk in men who received X-ray treatments to the chest and adjacent body areas. Risk was increased only from 20 to 35 years after initial exposure from either radiographic examinations or X-ray treatments, and declined after three to four decades since last exposure, suggesting a wave of increased risk of finite duration following exposure. The doses of radiation received could not be estimated precisely, but those from diagnostic procedures were likely similar to those received by prepubertal females in prior studies, and the results of those and the present investigation are compatible. The carcinogenic effects of ionizing radiation may be similar in the male and prepubertal female breast. " 1994 Rapid Communications of Oxford Ltd.",,,,,,"10.1007/BF01830721",,,"http://hdl.handle.net/20.500.12104/42391","http://www.scopus.com/inward/record.url?eid=2-s2.0-0028012560&partnerID=40&md5=463027961c2a181907800b56d84902a2",,,,,,"1",,"Cancer Causes & Control",,"

The relationship between diet and breast cancer in men (United States)

Objectives: The purpose of this paper was to investigate the relationship between food and beverage consumption and the development of breast cancer in men. Methods: Possible relationships of dietary factors to risk of breast cancer in men were assessed in a case-control study conducted between 1983 and 1986. Cases (N = 220) were ascertained from ten population-based cancer registries. Controls (N = 291) were selected by random-digit dialing (< age 65) and from Health Care Financing Administration Medicare beneficiary lists (? age 65). Results: No trends in risk were observed with increasing intakes of specific foods, except for an increase in risk with citrus fruits. No increase in risk with increasing amounts of specific fats, vitamins, or minerals or with amounts of protein, fiber, carbohydrate, starches, nitrites, or alcohol consumed was observed, except for an increase in risk with dietary vitamin C consumption. A decreasing trend in risk with dietary niacin and with coffee and an increasing trend in risk with tea consumption were observed. No associations were found with use of any dietary supplements, including vitamin C. Conclusions: The observed associations are not consistent with findings from studies of breast cancer in women and probably do not represent causal relationships. Dietary factors are unlikely to be strong determinants of breast cancer in men

Seismological studies of ZZ Ceti stars

Background. The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed about 90% of the worldwide epidemiological evidence on the relation between risk of breast cancer and use of hormone replacement therapy (HRT). Methods. Individual data on 52,705 women with breast cancer and 108,411 women without breast cancer from 51 studies in 21 countries were collected, checked, and analysed centrally. The main analyses are based on 53,865 postmenopausal women with a known age at menopause, of whom 17,830 (33%) had used HRT at some time. The median age at first use was 48 years, and 34% of ever-users had used HRT for 5 years or longer. Estimates of the relative risk of breast cancer associated with the use of HRT were obtained after stratification of all analyses by study, age at diagnosis, time since menopause, body-mass index, parity, and the age a woman was when her first child was born. Findings. Among current users of HRT or those who ceased use 1-4 years previously, the relative risk of having breast cancer diagnosed increased by a factor of 1.023 (95% CI 1.011-1.036; 2p = 0.0002) for each year of use; the relative risk was 1.35 (1.21-1.49; 2p = 0.00001) for women who had used HRT for 5 years or longer (average duration of use in this group 11 years). This increase is comparable with the effect on breast cancer of delaying menopause, since among never-users of HRT the relative risk of breast cancer increases by a factor of 1.028 (95% CI 1.021-1.034) for each year older at menopause. 5 or more years after cessation of HRT use, there was no significant excess of breast cancer overall or in relation to duration of use. These main findings did not vary between individual studies. Of the many factors examined that might affect the relation between breast cancer risk and use of HRT, only a woman's weight and body-mass index had a material effect: the increase in the relative risk of breast dancer associated with long durations of use in current and recent users was greater for women of lower than of higher weight or body-mass index. There was no marked variation in the results according to hormonal type or dose but little information was available about long durations of use of any specific preparation. Cancers diagnosed in women who had ever used HRT tended to be less advanced clinically than those diagnosed in never-users. In North America and Europe the cumulative incidence of breast cancer between the ages of 50 and 70 in never-users of HRT is about 45 per 1000 women. The cumulative excess numbers of breast cancers diagnosed between these ages per 1000 women who began use of HRT at age 50 and used it for 5, 10, and 15 years, respectively, are estimated to be 2 (95% CI 1-3), 6 (3-9), and 12 (5-20). Whether HRT affects mortality from breast cancer is not known. Interpretation. The risk of having breast cancer diagnosed is increased in women using HRT and increases with increasing duration of use. This effect is reduced after cessation of use of HRT and has largely, if not wholly, disappeared after about 5 years. These findings should be considered in the context of the benefits and other risks associated with the use of HRT

Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Collaborative Group on Hormonal Factors in Breast Cancer

BACKGROUND The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on the relation between breast cancer risk and use of hormonal contraceptives. METHODS Individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 studies conducted in 25 countries were collected, checked, and analysed centrally. Estimates of the relative risk for breast cancer were obtained by a modification of the Mantel-Haenszel method. All analyses were stratified by study, age at diagnosis, parity, and, where appropriate, the age a woman was when her first child was born, and the age she was when her risk of conception ceased. FINDINGS The results provide strong evidence for two main conclusions. First, while women are taking combined oral contraceptives and in the 10 years after stopping there is a small increase in the relative risk of having breast cancer diagnosed (relative risk [95 percent CI] in current users 1.24 [1.15-1.33], 2p<0.00001; 1-4 years after stopping 1.16 [1.08-1.23], 2p=0.00001; 5-9 years after stopping 1.07 [1.02-1.13], 2p=0.009). Second, there is no significant excess risk of having breast cancer diagnosed 10 or more years after stopping use (relative risk 1.01 [0.96-1.05], NS). The cancers diagnosed in women who had used combined oral contraceptives were less advanced clinically than those diagnosed in women who had never used these contraceptives for ever-users compared with never-users, the relative risk for tumours that had spread beyond the breast compared with localised tumours was 0.88 (0.81-0.95; 2p=0.002). There was no pronounced variation in the results for recency of use between women with different background risks of breast cancer, including women from different countries and ethnic groups, women with different reproductive histories, and those with or without a family history of breast cancer. The studies included in this collaboration represent about 90 percent of the epidemiological information on the topic, and what is known about the other studies suggests that their omission has not materially affected the main conclusions. Other features of hormonal contraceptive use such as duration of use, age at first use, and the dose and type of hormone within the contraceptives had little additional effect on breast cancer risk, once recency of use had been taken into account. Women who began use before age 20 had higher relative risks of having breast cancer diagnosed while they were using combined oral contraceptives and in the 5 years after stopping than women who began use at older ages, but the higher relative risks apply at ages when breast cancer is rare and, for a given duration of use, earlier use does not result in more cancers being diagnosed than use beginning at older ages. Because breast cancer incidence rises steeply with age, the estimated excess number of cancers diagnosed in the period between starting use and 10 years after stopping increases with age at last use: for example, among 10 000 women from Europe or North America who used oral contraceptives from age 16 to 19, from age 20 to 24, and from age 25 to 29, respectively, the estimated excess number of cancers diagnosed up to 10 years after stopping use is 0.5 (95 percent CI 0.3-0.7), 1.5 (0.7-2.3), and 4.7 (2.7-6.7). Up to 20 years after cessation of use the difference between ever-users and never-users is not so much in the total number of cancers diagnosed, but in their clinical presentation, with the breast cancers diagnosed in ever-users being less advanced clinically than those diagnosed in never-users. The relation observed between breast cancer risk and hormone exposure is unusual, and it is not possible to infer from these data whether it is due to an earlier diagnosis of breast cancer in ever-users, the biological effects of hormonal contraceptives, or a combination of reasons..

Discovery of common and rare genetic risk variants for colorectal cancer

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P &amp;lt; 5 × 10 −8 , bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development. © 2018, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply