Metal exposures, endocrine factors and cancer risk
- Autores: Esther García García-Esquinas
- Directores de la Tesis: Marina Pollán Santamaría (dir. tes.), Ana Navas Acien (dir. tes.)
- Lectura: En la Universidad Autónoma de Madrid ( España ) en 2014
- Idioma: inglés
- Tribunal Calificador de la Tesis: Fernando Rodríguez Artalejo (presid.), Custodia García Jiménez (secret.), Carmen Guillén Ponce (voc.), Henrique Barros (voc.), Gonzalo López Abente Ortega (voc.)
- Programa de doctorado: Programa Oficial de Doctorado en Medicina Preventiva y Salud Pública
- Materias:
- Enlaces
- Tesis en acceso abierto en: Biblos-e Archivo
- Resumen
Cancer is one of the leading causes of death both in men and women in the world, particularly in undeveloped countries. Around 90% of cancers are linked to some type of environmental or lifestyle factor, including use of tobacco, consumption of certain foods or exposure to substances in air, water and soil. Cancer epidemiology studies have played an important role in identifying many of these environmental factors and translating this knowledge into prevention strategies. However, in spite of extensive investigations, some gaps in the state of knowledge exist, and for some cancers like prostate cancer, few environmental factors have been identified. The main objective of this thesis is to address the influence of some of these environmental and lifestyle factors on cancer development.
Data from a cohort study (Strong Heart Study) and a case-control study (MCCSpain) have been analyzed. The Strong Heart Study is the largest epidemiologic study of cardiovascular disease in American Indian populations ever undertaken. Initially conducted in 1989 to 1991, the Strong Heart Study recruited 4,549 participants from 13 tribes and communities in Arizona, Oklahoma, North and South Dakota and followed them up through 2008. MCC-Spain is a population-based multicase-control study that recruited incident, histologically confirmed cases of breast (N=1743) and prostate (N=1113) cancers from 22 Spanish public hospitals between 2008 and 2013. Controls (N=1880 for breast and 1460 for prostate) were frequency-matched to the cases, taking into account age, sex and region. This thesis first evaluates the association between low-to-moderate levels of exposure to certain metals (arsenic and cadmium) and cancer mortality in the Strong Heart Study population, using Cox proportional hazards models. Then, it investigates the role of diabetes and obesity in the development of hormone-dependent tumors (breast and prostate) in MCC-Spain, using logistic mixed models that included the interviewer or the study region as random effect terms.
The median (interquartile range) urine concentration for inorganic plus methylated arsenic species was 9.7 (5.8-15.9) ¿g/g creatinine. The adjusted hazard ratios (95%CI) comparing the 80th versus 20th percentiles of arsenic were 1.14 (0.92-1.41) for overall cancer, 1.56 (1.02-2.39) for lung cancer, 1.34 (0.66-2.72) for liver cancer, 3.30 (1.28-8.48) for prostate cancer and 0.44 (0.14-0.96) for lymphatic and hematopoietic cancers. The median (interquartile range) urine cadmium concentration was 0.93 (0.61-1.46) ¿g/g creatinine. The adjusted hazard ratios (95%CI) comparing the 80th versus 20th percentiles of cadmium were 1.30 (1.09-1.55) for total cancer mortality, 2.27 (1.58-3.27) for lung cancer and 2.40 (1.24-1.96) for pancreas cancer mortality.
4 In postmenopausal women, the age at maximum height was inversely associated with the risk of breast cancer (OR per year:0.93; 95%CI:0.89-0.98), while an overall increased risk of this tumor was observed with increasing body mass index (OR2 units:1.10; 95%CI:1.05-1.15), waist circumference (OR10 cm : 1.04; 95%CI:0.99-1.20) and waist to hip ratio (OR0.10 units:1.20; 95%CI:1.03-1.41). In premenopausal women, the weight at age 45 (OR5 kgs:1.13; 95%CI:1.00-1.28) and the waist circumference were associated with breast cancer risk (OR10 cm waist circumference:1.18; 95%CI:0.98-1.42) after adjustment for body mass index. By intrinsic subtypes, in postmenopausal women weight gain since age 20 was associated with an increased risk of HR+/HER2- tumors in models that did not account for body mass index (OR5 kg:1.10; 95%CI:1.04-1.16), while displayed a negative association with HER2+ tumors ( p heterogeneity of effects= 0.05). Those variables associated to obesity earlier in like (¿weight at age 20¿ and ¿age at maximum weight) were associated with a decreased risk of more aggressive tumor subtypes (HER2+ and triple negative) in premenopausal but not postmenopausal women. In men, the age at maximum weight (OR5 years: 1.05; 95%CI: 1.00-1.10) and the waist to hip ratio (OR0.1 units:1.21; 95%CI:1.03-1.43) were associated with the risk of high-grade prostate tumors.
Self-reported diabetes was associated with an increased risk of triple negative breast tumors in postmenopausal women (OR:2.13; 95%CI:1.25-3.63). In this group of women, metformin use was associated with a decreased risk of HR+/HER2- tumors (ORper year:0.89; 95%CI:0.81-0.99), while use of sulfonylurea was associated with an increased risk of triple negative tumors (ORper year:1.10; 95%CI:1.00-1.20). Finally, an increased risk of postmenopausal breast cancer was observed in women under insulin treatment (OR:2.14; 95%CI:1.12-4.09), with a non-significant positive dose response association between years of insulin use and breast cancer risk (ORper year:1.10; 95%CI:0.98-1.23). For prostate cancer, a decreased risk of low-grade tumors was observed in men with diabetes (OR:0.64; 95%CI:0.46-0.89), and this protective effect was stronger as time since diagnosis increased (ORper year:0.97; 95%CI:0.84-1.00).
These results provide novel evidence about the influence of low-moderate arsenic and cadmium exposure levels on cancer mortality. Additionally, regarding the association of obesity and diabetes with hormone-dependent cancers (breast and prostate), they offer valuable information suggesting differences in the effect of these factors by tumor subtype.
