Alcohol, genetics and risk of breast cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial

Essentia Institute of Rural Health, Duluth, MN 55805, USA.
Breast Cancer Research and Treatment (Impact Factor: 3.94). 02/2012; 133(2):785-92. DOI: 10.1007/s10549-012-1972-1
Source: PubMed
We tested the hypothesis that genes involved in the alcohol oxidation pathway modify the association between alcohol intake and breast cancer. Subjects were women aged 55-74 at baseline from the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Incident breast cancers were identified through annual health surveys. Controls were frequency matched to cases by age and year of entry into the trial. A self-administered food frequency questionnaire queried frequency and usual serving size of beer, wine or wine coolers, and liquor. Three SNPs in genes in the alcohol metabolism pathway were genotyped: alcohol dehydrogenase 2, alcohol dehydrogenase 3, and CYP2E1. The study included 1,041 incident breast cancer cases and 1,070 controls. In comparison to non-drinkers, the intake of any alcohol significantly increased the risk of breast cancer, and this risk increased with each category of daily alcohol intake (OR 2.01, 95% CI 1.14, 3.53) for women who drank three or more standard drinks per day. Stratification by genotype revealed significant gene/environment interactions. For the ADH1B gene, there were statistically significant associations between all levels of alcohol intake and risk of breast cancer (all OR > 1.34 and all lower CI > 1.01), while for women with the GA or AA genotype, there were no significant associations between alcohol intake and risk of breast cancer. Alcohol intake, genes involved in alcohol metabolism and their interaction increase the risk of breast cancer in post-menopausal women. This information could be useful for primary care providers to personalize information about breast cancer risk reduction.

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    • "With few exceptions [5,46,47], our findings are consistent with prior studies that show a positive association between mammographic density and current alcohol intake [8,9,11,17,18,484950, although the precision for many of these estimates is highly variable [21]. In studies that examine beverage type [8,515253, the majority confirm a positive association between wine intake and mammographic density [8,9,18]. We found a positive association between wine intake and percent density; however, the association was attenuated after adjusting for age and BMI. "
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    • "The smallest study included n ¼ 556 women (Lenz et al., 2002) whereas the largest study included n ¼ 274 688 women (Tjonneland et al., 2007).showed that modest or high alcohol consumption was associated with a moderate increase in breast cancer risk (Allen et al., 2009;Beasley et al., 2010;Berstad et al., 2008;Chen et al., 2011;Deandrea et al., 2008;Duffy et al., 2009;Feigelson et al., 2003;Horn-Ross et al., 2004;Kabat et al., 2011;Lenz et al., 2002;Lew et al., 2009;Li et al., 2003Li et al., , 2009Li et al., , 2010Lin et al., 2005;Mattisson et al., 2004b;Mccarty et al., 2012;Morch et al., 2007;Petri et al., 2004;StolzenbergSolomon et al., 2006;Suzuki et al., 2005Suzuki et al., , 2010Tjonneland et al., 2006Tjonneland et al., , 2007Zhang &amp; Holman, 2011;Zhang et al., 2007). Several of the above studies examined also the association of alcohol consumption with breast cancer risk defined by estrogen receptor (ER) and progesterone receptor (PR) status and reported an increased risk of ER + (Chen et al., 2011;Deandrea et al., 2008;Kabat et al., 2011;Lew et al., 2009;Suzuki et al., 2005), ER + /PR + (Deandrea et al., 2008;Lew et al., 2009;Li et al., 2003Li et al., , 2010Suzuki et al., 2005;Zhang et al., 2007) and even PR + (Chen et al., 2011;Lew et al., 2009) breast cancers, further supporting the hypothesis that alcohol influences hormonal status through hormone-related mechanisms (such as increased estrogen and androgen levels;Singletary &amp; Gapstur 2001) leading to increased breast cancer risk. "
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    No preview · Article · Sep 2014 · International Journal of Food Sciences and Nutrition
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    • "Extending these studies to uncontrolled environmental effects on outbred populations – specifically, humans – poses technical and analytical challenges that have only recently become tractable. A flurry of recent studies report the effects of observed environmental factors on allelotypes of specific candidate genes, including ADH1B genotype  alcohol use interaction effects on breast cancer risk (McCarty et al., 2012) and effects on behaviour of dopamine D4 receptor (DRD4) copynumber polymorphism interactions with measured environmental factors (alcohol use, Creswell et al., 2012; socioeconomic status, Sweitzer et al., 2012). In the present study, we undertook an agnostic search of all agecorrelated expression phenotypes by performing formal tests of polygenic G  AI. "
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