Hormone replacement therapy, body mass, and the risk of colorectal cancer among postmenopausal women from Germany

Abstract

Previous studies have reported inconsistent results regarding the modifying effect of hormone replacement therapy (HRT) on the association of body mass index (BMI) and the risk of colorectal cancer (CRC) among postmenopausal women. We assessed the use of HRT and BMI in 208 postmenopausal women with histologically confirmed incident CRC and 246 controls in a population-based case -control study in Germany (DACHS study). Ever use of HRT was strongly associated with reduction of CRC risk (adjusted odds ratio 0.41, 95% confidence interval 0.25 -0.67). Among nonusers of HRT, risk of CRC was strongly increased in women with BMI 27 to o30 kg m À2 (2.76, 1.07 -7.12) and obese women (3.30, 1.25 -8.72), when compared with women with BMI o23 kg m À2 (P for trend o0.01). BMI was not associated with risk of CRC among HRT users (P for interaction o0.01). In contrast to most other studies, a positive association of BMI and CRC risk was found among nonusers of HRT, but not among users of HRT. The reasons for the inconsistency of results regarding the potential risk modifying effect of postmenopausal hormones in the association of BMI with CRC remain inconclusive and require further study.

Menopausal hormone therapy and risks of colorectal adenomas and cancers in the French E3N prospective cohort: true associations or bias?

“…We investigated this hypothesis by testing an interaction between history of colonoscopies and MHT use; the inverse association between estrogens alone and risk of colorectal cancers was restricted to women who had a personal history of colonoscopy, although the interaction term was only borderline statistically significant. However, this interaction could only explain part of our results and was not observed in two previous studies which investigated it [24,47].…”

“…Finally, two recent meta-analyses reported a significantly decreased risk of colorectal cancer associated with both estrogens alone and estrogens combined with progestagens [16,17]. Results concerning the effect of the route of administration of estrogens [13,[18][19][20][21][22] or the site of the tumour [12,13,[23][24][25] are also conflicting.…”

Association of genetic polymorphisms in ESR2, HSD17B1, ABCB1, and SHBG genes with colorectal cancer risk

“…The identification of ER2 (ER-b) as the predominant subtype present in both colon epithelial cell lines and human colon epithelium samples (Arai et al 2000, Xie et al 2004 as well as its downregulated expression on tumor cells compared with normal have pointed out that ER2 might have a selective and inhibitory effect on the proliferation of colon epithelial cells (Foley et al 2000). Later on, epidemiological and clinical studies have reported that postmenopausal women undergoing hormone replacement therapy (HRT) have a decreased risk of developing CRC (La Vecchia et al 2005, Hoffmeister et al 2007. In support of this anti-proliferative action of estrogens in colonic cells, Foley et al (2000) also reported that ESR2 expression level correlate with CRC patient survival.…”

Modification of menopausal hormone therapy-associated colorectal cancer risk by polymorphisms in sex steroid signaling, metabolism and transport related genes

“…Women recruited between January 2003 and October 2004 provided basic information about MHT, including start, end, and duration of use A Rudolph et al: Polymorphisms, HT and colorectal cancer risk www.endocrinology-journals.org (Hoffmeister et al 2007). Between November 2004 and December 2007, detailed information for each period of MHT was collected during the interview.…”