Sara S. Strom

Detectable clonal mosaicism from birth to old age and its relationship to cancer

We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5–10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2–3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6–18).

Mortality After Cure of Testicular Seminoma

PURPOSE To determine the incidence of potentially treatment-related mortality in long-term survivors of testicular seminoma treated by orchiectomy and radiation therapy (XRT). PATIENTS AND METHODS From all 477 men with stage I or II testicular seminoma treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX) with post-orchiectomy megavoltage XRT between 1951 and 1999, 453 never sustained relapse of their disease. Long-term survival for these 453 men was evaluated with the person-years method to determine the standardized mortality ratio (SMR). SMRs were calculated for all causes of death, cardiac deaths, and cancer deaths using standard US data for males. RESULTS After a median follow-up of 13.3 years, the 10-, 20-, 30-, and 40-year actuarial survival rates were 93%, 79%, 59%, and 26%, respectively. The all-cause SMR over the entire observation interval was 1.59 (99% CI, 1.21 to 2.04). The SMR was not excessive for the first 15 years of follow-up: SMR, 1.30 (95% CI, 0.93 to 1.77); but beyond 15 years the SMR was 1.85 (99% CI, 1.30 to 2.55). The overall cardiac-specific SMR was 1.61 (95% CI, 1.21 to 2.24). The cardiac SMR was significantly elevated only beyond 15 years (P <.01). The overall cancer-specific SMR was 1.91 (99% CI, 1.14 to 2.98). The cancer SMR was also significant only after 15 years of follow-up (P <.01). An increased mortality was evident in patients treated with and without mediastinal XRT. CONCLUSION Long-term survivors of seminoma treated with post-orchiectomy XRT are at significant excess risk of death as a result of cardiac disease or second cancer. Management strategies that minimize these risks but maintain the excellent hitherto observed cure rates need to be actively pursued.

Phytoestrogen intake and prostate cancer: a case-control study using a new database.

In the last several years, attention has been focused on comparing the Western diet, which is rich in fat, protein, and refined carbohydrates, with the Asian diet, which is rich in phytoestrogens, as a possible explanation for the contrasting rates of clinically relevant prostate cancer. Phytoestrogens, plant-derived nutrients, include several isoflavones, flavonoids, lignans, phytosterols, and coumestans, some of which have been postulated as having anticarcinogenic properties. Using a new database, we examined the role of phytoestrogen intake and prostate cancer risk in 83 Caucasian cases and 107 controls. Controls reported consuming higher amounts of foods containing genistein, daidzein, and coumestrol and lower amounts of foods containing campesterol and stigmasterol. Multivariate analysis, after adjustment for age, family history of prostate cancer, alcohol consumption, and total calorie intake, showed an inverse association between coumestrol (p = 0.03) and daidzein (p = 0.07) and prostate cancer risk. Genistein, the most studied phytoestrogen, showed a slight protective effect (p = 0.26). However, a positive association was found between campesterol (p = 0.08) and stigmasterol (p = 0.03) and risk of prostate cancer. These results are suggestive of a possible relationship between phytoestrogen intake and prostate cancer risk. Larger comprehensive studies are needed to further refine the role of phytoestrogen intake in prostate cancer risk.

The landscape of recombination in African Americans

Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P value < 10−245). We identify a 17-base-pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of PRDM9 alleles common in West Africans and rare in Europeans. Sites of this motif are predicted to be risk loci for disease-causing genomic rearrangements in individuals carrying these alleles. More generally, this map provides a resource for research in human genetic variation and evolution.

Effects of Nativity, Age at Migration, and Acculturation on Smoking Among Adult Houston Residents of Mexican Descent

OBJECTIVES We investigated differences in smoking behaviors between US-and Mexican-born ever smokers and examined the influence of US culture on smoking initiation. METHODS Participants were 5030 adults of Mexican descent enrolled in an ongoing population-based cohort in Houston, Tex. RESULTS More men than women reported current smoking; rates among US-born women were higher than those among Mexican-born women. Smoking rates among US-born men were higher than earlier published rates among Hispanics and non-Hispanic Whites but similar to rates among African Americans. Current smoking rates among Mexican-born women were lower than published rates for Hispanics, non-Hispanic Whites, and African Americans. Older age, male gender, a higher level of acculturation, more than a high school education, and residing in a census tract with a higher median age predicted history of smoking among US-born participants. Among Mexican-born participants, older age, male gender, a higher level of acculturation, and younger age at migration predicted history of smoking. CONCLUSIONS Smoking interventions for people of Mexican descent should be tailored according to gender, nativity, and acculturation level and should target all ages, not just young people.

Thyroid hormone and breast carcinoma: Primary hypothyroidism is associated with a reduced incidence of primary breast carcinoma

To investigate the role of primary hypothyroidism (HYPT) on breast carcinogenesis, the authors evaluated 1) the association between HYPT and a diagnosis of invasive breast carcinoma and 2) the clinicopathologic characteristics of breast carcinoma in patients with HYPT.

Birthplace, Years of Residence in the United States, and Obesity Among Mexican-American Adults

Objective: To evaluate the association between birthplace (Mexico or U.S.) and obesity in men and women and to analyze the relationship between duration of U.S. residency and prevalence of obesity in Mexican immigrants.

Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21

In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10−13). The frequency of the risk allele is ∼5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations.

Leptin and prostate cancer

Higher prostate cancer mortality rates among US immigrants from countries with lower rates suggest environmental influences on prostate carcinogenesis (e.g., diet, body composition).

Development of a database for assessing dietary phytoestrogen intake

For the past two decades, epidemiologists have observed lower risks of lung, breast, prostate, colon, and other cancers in populations that frequently consume fruits and vegetables. Numerous phytoestrogens have been shown to be anticarcinogenic under experimental conditions and may account for at least part of the cancer-prevention effects of fruit and vegetable consumption. These plant constituents include isoflavonoids, coumestans, lignans, phytosterols, and flavonoids. DietSys, the nutrient analysis program associated with the National Cancer Institute Health Habits and History Questionnaire (HHHQ), and other nationally available nutrient analysis databases do not fully assess these constituents. Therefore, we modified DietSys to include these components in foods on the basis of published values. In addition, as part of an epidemiological study of prostate cancer, we modified the food-frequency component of the HHHQ to include the main foods contributing to phytoestrogen intake. Although there are limitations to the consistency and quality of many of the values because they were gathered from a variety of sources, our approach should provide a useful first tool for assessing the epidemiological association between phytoestrogen consumption and cancer risk. Furthermore, this work has already facilitated the identification of the major dietary contributors with phytoestrogen activity and prioritized future laboratory analyses of specific foods toward the development of a more complete and accurate database.