Building a funded research program in cancer health disparities: considerations for young investigators.

A workshop entitled "Building a funded research program in cancer health disparities" was held at the 38th Annual American Society of Preventive Oncology (ASPO) Meeting. Organized by the Junior Members Interest Group, the session addressed topics relevant to career development for cancer disparities investigators. Such considerations include the development of research programs on a backdrop of existing multi- and transdisciplinary teams, recognizing opportunities for advancing their research, given the growth of consortia-related research, and development of effective community-based partnerships. Key strategies for developing a sustainable career in cancer health disparities in the current environment include the need to effectively engage with communities, appreciate the value of team science and develop cross-discipline collaborations, and navigate the use and utility of consortia for disparities research. Academic considerations related to earning tenure and promotion that may be faced by the junior investigator in cancer health disparities were also discussed. This report may serve to both educate and provide lessons for early-stage investigators who wish to tackle complex scientific questions while developing their careers in cancer health disparities.

Multivariate association analysis of the components of metabolic syndrome from the Framingham Heart Study.

Metabolic syndrome, by definition, is the manifestation of multiple, correlated metabolic impairments. It is known to have both strong environmental and genetic contributions. However, isolating genetic variants predisposing to such a complex trait has limitations. Using pedigree data, when available, may well lead to increased ability to detect variants associated with such complex traits. The ability to incorporate multiple correlated traits into a joint analysis may also allow increased detection of associated genes. Therefore, to demonstrate the utility of both univariate and multivariate family-based association analysis and to identify possible genetic variants associated with metabolic syndrome, we performed a scan of the Affymetrix 50 k Human Gene Panel data using 1) each of the traits comprising metabolic syndrome: triglycerides, high-density lipoprotein, systolic blood pressure, diastolic blood pressure, blood glucose, and body mass index, and 2) a composite trait including all of the above, jointly. Two single-nucleotide polymorphisms within the cholesterol ester transfer protein (CETP) gene remained significant even after correcting for multiple testing in both the univariate (p < 5 x 10-7) and multivariate (p < 5 x 10-9) association analysis. Three genes met significance for multiple traits after correction for multiple testing in the univariate analysis, while five genes remained significant in the multivariate association. We conclude that while both univariate and multivariate family-based association analysis can identify genes of interest, our multivariate approach is less affected by multiple testing correction and yields more significant results.

No association between phosphatase and tensin homolog genetic polymorphisms and colon cancer.

AIM: To investigate the association between single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homolog (PTEN) tumor suppressor gene and risk of colon cancer. METHODS: We utilized a population-based case-control study of incident colon cancer individuals (n = 421) and controls (n = 483) aged > or = 30 years to conduct a comprehensive tagSNP association analysis of the PTEN gene. RESULTS: None of the PTEN SNPs were statistically significantly associated with colon cancer when controlled for age, gender, and race, or when additionally adjusted for other known risk factors (P > 0.05). Haplotype analyses similarly showed no association between the PTEN gene and colon cancer. CONCLUSION: Our study does not support PTEN as a colon cancer susceptibility gene.

Reproductive and hormonal risk factors for ductal carcinoma in situ of the breast.

One-fifth of all newly diagnosed breast cancer cases are ductal carcinoma in situ (DCIS), but little is known about DCIS risk factors. Recent studies suggest that some subtypes of DCIS (high grade or comedo) share histopathologic and epidemiologic characteristics with invasive disease, whereas others (medium or low grade or non-comedo) show different patterns. To investigate whether reproductive and hormonal risk factors differ among comedo and non-comedo types of DCIS and invasive breast cancer (IBC), we used a population-based case-control study of 1,808 invasive and 446 DCIS breast cancer cases and their age and race frequency-matched controls (1,564 invasive and 458 DCIS). Three or more full-term pregnancies showed a strong inverse association with comedo-type DCIS [odds ratio (OR), 0.53; 95% confidence interval (95% CI), 0.30-0.95] and a weaker inverse association for non-comedo DCIS (OR, 0.73; 95% CI, 0.42-1.27). Several risk factors (age at first full-term pregnancy, breast-feeding, and age at menopause) showed similar associations for comedo-type DCIS and IBC but different associations for non-comedo DCIS. Ten or more years of oral contraceptive showed a positive association with comedo-type DCIS (OR, 1.31; 95% CI, 0.70-2.47) and IBC (OR, 2.33; 95% CI, 1.06-5.09) but an inverse association for non-comedo DCIS (OR, 0.51; 95% CI, 0.25-1.04). Our results support the theory that comedo-type DCIS may share hormonal and reproductive risk factors with IBC, whereas the etiology of non-comedo DCIS deserves further investigation.