University of Pittsburgh Cancer Institute (UPCI)

Cancer Epidemiology

Image of GlobeThe Cancer Epidemiology Group studies cancer causation in terms of exposure and personal susceptibility. Cancer Epidemiology works to exploit measurable physiologic changes that possibly mediate the effects of exposure and uses state-of-the-art techniques to characterize personal susceptibility associated with genetic and epigenetic profiles. Cancer Epidemiology areas of emphasis include tobacco- and hormone-related processes in relationship to lung, head and neck, ovary, breast, and prostate cancer.

Selected Publications

Breast Cancer

  • Triple-negative (estrogen receptor [ER], progesterone receptor, and HER2 negative) breast cancer occurs disproportionately among African-American women compared with white women and is associated with a worse prognosis than ER-positive (ER+) breast cancer. Hormonally mediated risk factors may be differentially related to risk of triple-negative and ER+ breast cancers. Investigators found that association between parity and breast cancer risk differs appreciably for ER+ and triple-negative breast cancers (Phipps, J Natl Cancer Inst. 103:470-7, 2011).
  • Aromatase inhibitors (AIs) have become the standard adjuvant therapy of postmenopausal breast cancer survivors. AIs induce a reduction of bioavailable estrogens by inhibiting aromatase, which would be expected to induce alterations in body composition, more extensive than induced by menopause. AI users demonstrated maintenance of total body fat, an increase in lean body mass and free testosterone levels, and a decrease in sex hormone binding globulin levels compared to no-AI users (van Londen, Breast Cancer Res Treat. 2011 Jan;125(2):441-6).
  • Several mechanisms have been proposed to explain tamoxifen resistance of estrogen receptor (ER) -positive tumors, but a clinically useful explanation for such resistance has not been described. Because the ER is the treatment target for tamoxifen, a linear association between ER expression levels and the degree of benefit from tamoxifen might be expected. Data suggest that low-level expression of the estrogen receptor 1 (ESR1) mRNA is a determinant of tamoxifen resistance in ER-positive breast cancer. Strategies should be developed to identify, treat, and prevent such tumors (Kim, J Clin Oncol. 29:4160-7, 2011).

Endometrial Cancer

  • Malignant mixed mullerian tumors (MMMTs) are an aggressive subtype of endometrial cancer (EC). Investigators compared recurrence-free survival, disease-specific survival, and overall survival among EC subtypes. In this first retrospective study suggest that certain survival outcomes are similar among MMMT, high-grade endometrioid, clear cell, and papillary serous (PS) ECs (Felix, Int J Gynecol Cancer 21:877-84, 2011).

Prostate Cancer

  • Recent genome-wide association studies implicate some regions of chromosome 8q24 in the disparate prostate cancer susceptibility in men of European and African ancestry. An association of chromosome 8q24 variants with increased prostate cancer risk in Tobago men of mainly west African ancestry and the higher frequency of the risk alleles in controls in populations of African ancestry further strengthens the possible role of this genomic region in the disproportionate higher burden of prostate cancer in men of African ancestry (Okobia, Prostate 71:1054-63, 2011).

Esophageal Cancer

  • N'-Nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are tobacco-specific nitrosamines. NNN and NNK can induce cancers of the esophagus and lung, respectively, in laboratory animals, but data on human esophageal cancer are lacking. The association between levels of NNN and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), an NNK metabolite, in urine samples collected before diagnosis and risk of esophageal cancer was examined in patients with esophageal cancer and individually matched healthy subjects who were current smokers, from a cohort of 18244 Chinese men in Shanghai, China, followed from 1986 to 2008. Smokers with highest tertile of urinary NNN experienced more than 15-fold increased risk of developing esophageal cancer relative to smokers with the lowest tertile of NNN. These findings along with results of previous studies in laboratory animals support a significant and unique role of NNN in esophageal carcinogenesis in humans. (Yuan, Carcinogenesis. 2011 Sep;32(9):1366-71).

Lung Cancer

  • DNA repair and cell cycle control play an important role in the repair of DNA damage caused by cigarette smoking. Given this role, functionally relevant single nucleotide polymorphisms (SNPs) in genes in these pathways may well affect the risk of smoking-related lung cancer. Data suggests that variation in DNA repair and cell cycle control pathway genes is associated with smoking-related lung cancer risk. Additionally, combining genotype information for SNPs in these pathways may assist in classifying current and ex-cigarette smokers according to lung cancer risk (Buch, Mol Carcinog. 2011 Oct 4).
  • Both polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamine NNK are believed to be among the principal causative agents for lung cancer in smokers, but no epidemiologic studies have evaluated the relationship of PAH and NNK uptake and metabolism to lung cancer. In this study, urinary PheT and total NNAL, biomarkers of PAH and NNK, respectively were quantified in 476 smokers who subsequently developed lung cancer and an equal number of smokers as controls who remained free of lung cancer from a cohort of 18,244 Chinese men in Shanghai, China, after up to 20 years of follow-up. Smokers in the top 25th percentile of urinary PheT and total NNAL experienced doubled risk of lung cancer than smokers in the bottom 25th percentile of these biomarkers, respectively, otherwise comparable in smoking intensity and duration as well as urinary levels of cotinine, a nicotinine metabolite, This study demonstrated that urinary PheT, total NNAL and total cotinine are independent risk factors for lung cancer in smokers.(Yuan, Cancer Res. 2011 Nov 1;71(21):6749-57).
  • Green tea contains high concentrations of tea polyphenols that have shown inhibitory effects against the development, progress, and growth of carcinogen-induced tumors in animal models at different organ sites, including the esophagus and lung. Green tea polyphenols also are shown to suppress cell proliferation and induce apoptosis. This article reviews data on the cancer-preventive activities of green tea extract and green tea polyphenols and possible mechanisms against the esophageal and lung carcinogenesis in experimental animals, and summarizes the current knowledge from epidemiological studies on the relationship between green tea consumption and esophageal and lung cancer risk in humans. (Yuan,JM. Mol Nutr Food Res. 2011 Jun;55(6):886-904).